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Dream Contents and Failing Memories
Abstract
Mentation during sleep states is thought to originate in an activation of brain circuits that encode inherited and experiential memories. Spontaneous degradation of the strengths of synapses occurs in all brain circuits because of "turnover" of molecules essential for synaptic function. In circuits employed frequently during waking, synaptic strengths are refreshed and maintained in their dedicated or functional ranges largely through use, by virtue of activity-dependent synaptic plasticity. In circuits employed infrequently during waking, synaptic strengths are refreshed largely during sleep, by circuit activations induced by spontaneous, self-generated, largely low-frequency brain waves, also by virtue of activity-dependent synaptic plasticity. The outputs of circuits activated during sleep do not necessarily rise to the level of 'unconscious' awareness. Such an absence of awareness of the outputs of individual circuits, that is, an absence of dreaming, is proposed to be the primitive condition in animals that sleep. On the other hand, temporal binding of these outputs is accompanied by the thoughts and perceptions of dreams, which is proposed to be the advanced condition. Linking or serial ordering of otherwise 'static' thoughts and perceptions gives rise to continuous, often narrative and veridical, dreams. In all cases, dream contents are derived from the memories--not necessarily veridical--encoded in the reinforced circuitry. In the absence of synaptic strength refreshments during sleep, synaptic strengths in infrequently used circuits would weaken and the circuits would become incompetent, with their encoded memories degraded or lost. Maintenance of synaptic strengths in infrequently used circuitry during sleep apparently does not always achieve perfection. Weakened synapses begin to occur in circuits in appreciable numbers in children after the age of about 5 years. When these 'incompetent' circuits (with weakened synapses) are activated during sleep, there are minimal influences on dream contents, namely, distortions that make some objects, such as animals, faces, and scenes, unrecognizable. As weakened synapses increase in numbers with age, the numbers of distorted objects in dreams also increase. In adults, people in as many as 80% of dreams may be unrecognizable. Besides the normal weakening of synaptic strengths, some synapses become defective, in consequence of deleterious, adventitious, exogenous influences, for example, radiation. As these faulty synapses accumulate in old memories, activation of circuits incorporating them during sleep leads to dreams with incoherent, bizarre, or impossible contents. The infrequent activation of such old, incompetent circuits in some waking conditions leads to false memories, delusions, or hallucinations.
... They are least efficient in reinforcing individual component circuits of events, and most efficient in temporally binding these circuits to form the events. 20,21 In essence, then, the most efficient memory processing in mammals and birds is proposed to be a two-step process: individual component circuits are reinforced primarily by slow waves during NREM sleep, while the reinforced circuits are temporally bound by fast waves, acting over the entire cortical mantle and other regions (see [25]), during REM sleep. In the absence of REM sleep, the entire process can be accomplished by the primitive mechanisms of NREM sleep, alone, merely less efficiently. ...
... NREM sleep remains highly efficient in uncoordinated reinforcement. The latter is thought to be a gradual process, probably occurring in many subthreshold steps, and with 'dedicated' values of synaptic strengths covering a range, the 'synaptic modification range' (see [25]). Evolution of the two sleep states is treated elsewhere. ...
... 20,21 This proposed mechanism of uncoordinated reinforcement, followed or accompanied by coordinated reinforcement, during sleep, is thought to act unselectively on most stored long-term memories. The exceptions hinge on little-understood processes that are involved in selecting and temporally binding memories that become incorporated into dreams (including, principally, those most recent, of emotional concern, and/or with significant survival value; see [25]). It is not meant to imply, however, that once entered into the long-term repository, memories are permanent and immutable. ...
A major controversy over REM sleep's role in memory processing may owe to inadequate allowances for the highly conservative nature of evolutionary adaptations. The controversy hinges on whether NREM sleep, alone, retains primitive memory processing capabilities. The selective pressure for primitive sleep, is thought to have been the need to obviate conflicts between enormous neural processing requirements of complex visual analysis and split-second control of movements, on the one hand, and memory processing, on the other. The most efficient memory processing during mammalian and avian sleep appears to be a two-step process: synapses in individual component circuits of events are reinforced primarily by slow brain waves during NREM sleep, with the reinforced components temporally bound by fast waves, and manifested as dreams, during REM sleep. This dual action could account for partitioning of sleep periods into multiple NREM-REM cycles. It is proposed that in the absence of REM sleep, all needed memory processing can be accomplished by NREM sleep, alone, though less efficiently. Many symptoms of fatal familial insomnia are attributed to subnormal nightly reinforcement of brain circuitry because of almost total loss of sleep, and compensatory responses thereto during waking. During this disorder, sensory circuitry seemingly is spared by virtue of its supernormal reinforcement during almost continuous waking. Contrariwise, sparing of an adult's 'higher faculties' in encephalitis lethargica appears to owe to supernormal circuit reinforcement during almost continuous sleep.
... Memory reinforcement during primitive sleep, in whatever degree, would have had to be accomplished by these " slow waves. " The more complex matter of memory consolidation during sleep is treated elsewhere [16]. At the present time, sleep in mammals and birds is partitioned into two major states. ...
... These primarily reinforce individual circuit components (fragments) of memories, which are inherently unable to penetrate consciousness. The small amounts of lower amplitude fast waves (e.g., " ripples " ), that are present during NREM sleep, apparently give rise to the lesser numbers of NREM dreams, including those that are described as 'thoughtful' [16,17]. These proposals for the origin and function of primitive sleep do not preclude subsequent or concomitant evolution of secondary functions that may have become essential. ...
The development of neural multifunctionality - given brain regions carrying out more than one function - conferred great efficiency on brain function at early stages of evolution. This applied to animals that led relatively simple lives with few needs for long-term memories, such as many lower invertebrates - many molluscs, echinoderms, worms, etc. As more complex lifestyles and detailed focal vision evolved, needs for self-initiated and reflexive activities increased in frequency, and recognition of many locales, conspecifics, and other forms of life became essential. These developments were accompanied by greatly expanded needs for neural processing supporting sensory and motor activities, and establishing and storing long-term memories. Since these categories of neural processing occur in largely overlapping brain regions, brain functioning would have become increasingly maladaptive, had the evolution of these more complex lifestyles not been accompanied by compensating adaptations that obviated these potentially conflicting brain activities. These adaptations consisted of: first, restful waking; second, primitive sleep; and finally, fully developed sleep, with its specialized rapid-eye-movement and non-rapid-eye-movement states, that contribute to the maintenance of great efficiency of brain function. The only animals with detailed focal vision that can achieve highly efficient brain function without sleep, are those in which demands on memory processing are greatly reduced in consequence of routine, monotonous, almost purely reflexive lifestyles, with few needs for acquiring experiential long-term memories. The best known animals in this non-sleeping category are tunas and many sharks.
... Los recuerdo de los sueños, se han demostrado que están influenciados por muchos factores, como la actitud que se tiene hacia el soñar (entre más interesado o motivado estén los individuos, tendrán con más frecuencia la recuperación de los mismos), la personalidad (algunos rasgos psicológicos predispone a una mayor cantidad de evocación), el género (las mujeres son más a menudo capaces de recordar los sueños que los hombres) y las características emocionales de determinadas ensoñación. 42 Hay en particular, una relación positiva entre el mayor número de despertares nocturnos largos (diez o más segundos) y el número de los sueños que se logran recordar a la mañana siguiente, esto se ha observado tanto en individuos sanos y en pacientes con insomnio. Por el contrario, una relación negativa entre la frecuencia de recuerdo de los sueños y el número de movimientos periódicos de las piernas, se ha observado en pacientes con síndrome de piernas inquietas, probablemente debido a la corta duración de los despertares en estos pacientes (microdespertares de segundos). ...
The need for effective clinical interventions in chronic neurological diseases such as TBI and other variants of chronic neurological conditions have been called for in the literature. The cellular and neurochemical mechanisms addressed in recent literature have focused around three common themes that traverse all of these condition classes: immune and autoimmune mechanisms, inflammatory pathways and oxidative phosphorylation or other energy production damage. Limits to the effectiveness of pharmaceutical and surgical approaches are apparent, and complicated by the physiological interconnectedness of such pathways. A growing call for non-drug, non-surgical options has evolved due to the dangers of poly-pharmacy, the lifestyle illnesses, and emerging evidence pointing to functional measures and methods. This paper surveys and links selected studies of specific, measurable effects of brain injury on several body systems, and it indicates an emerging path toward outcome-based multifactorial functional neurological assessment and treatment of some of the sequelae of chronic TBI and mTBI) (mild traumatic brain injury).
This work proceeds from a deduction from evolutionary principles, that primitive sleep was non-uniform preceding the origin of the REM and NREM states. Coupling this conclusion with knowledge of the thermoregulatory responses to ambient temperatures by sleeping mammals, and indications that the REM and NREM sleep states originated during the evolution of warm-bloodedness in the Mid-to-Late Triassic period, implicates ambient temperature as the environmental variable responsible for the non-uniform condition of primitive sleep. Drawing on the paleontology and paleoecology of early ancestors of mammals, together with the uniquely warm and moist, moderate climates of the times, a sequence of selective pressures and resulting adaptations are proposed, leading to the origin of REM and NREM sleep and a basis for their cyclic alternation.
This chapter discusses the evolutionary aspects of sleep and its rapid-eye-movement (REM) and non-rapid-eye-movement (NREM) states. The neural adaptation of circuit multifunctionality confer great efficiency of brain function at early stages of evolution, in animals that lead relatively simple lives with few needs for long-term memories, such as many “lower” invertebrates. As more complex lifestyles and detailed focal vision evolved, needs for self-initiated and reflexive activities increased, and recognition of many locales, conspecifics, and other forms of life became essential. These developments are accompanied by greatly expanded needs for neural processing supporting sensory and motor activities, and establishing and storing long-term memories. Because these categories of neural processing occur largely in shared regions, brain functioning would have become increasingly maladaptive had the evolution of these more complex lifestyles not been accompanied by the evolution of compensating adaptations. In this treatment, the utility of an evolutionary approach has been illustrated—always seeking and mindful of differential adaptedness and underlying selective pressures—to guide research into the origin and functions of sleep and its REM and NREM states.
A partial analogy exists between the lifespan neuropsychological development of individuals and the biological evolution of species: In both of these major categories of growth, progressive emergence of wholes transcends inherently limited part-processes. The remarkably small purview of each moment of consciousness experienced by an individual may be a crucial aspect of maintaining organization in that individual's cognitive development, protecting it from combinatorial chaos. In this essay I summarize experimental psychology research showing that working memory capacity comprises the so-called magical number 7±2 items, not only for words and digits but for spatial items and other sorts of cognitive materials, and not only in humans but also in other species. This is so to such an extent that 7±2 may be a “constant of nature.” The small quantity range 7±2 independent items, which builds upon a more elementary, instantaneous working memory capacity of three or four items, is surprisingly independent of the time duration of a cognitive task. Moreover, it is largely independent of ontogeny. Explanations of these powerful facts about working memory are offered here within both a functionalistic framework and a framework of hypothetical neural processes. At the neural level, working memory dynamics may comprise certain brain wave harmonics or topological relationships in the sheetlike cortex. Within the functionalistic framework, I suggest an additional analogy, pertaining to cultural evolution, with Tom Gilbert's work on risk analysis and “the global problematic” that follows from unforeseen consequences of the expansiveness of human ambition. Several connections are drawn with ideas presented by participants in the Chicago Religion and Science Group about how theologies and sciences try to understand the possibility of adaptive exercises of human freedom in the face of the extreme finiteness of each human individual.
We review the literature on the neurobiology of rapid eye movement (REM) and non-rapid eye movement (NREM) sleep states and associated dreams. REM is associated with enhanced activation of limbic and amygdalar networks and decreased activation in dorsal prefrontal regions while stage II NREM is associated with greater cortical activation than REM. Not surprisingly, these disparate brain activation patterns tend to be associated with dramatically different dream phenomenologies and dream content. We present two recent studies which content-analyzed hundreds of dream reports from REM and NREM sleep states. These studies demonstrated that dreamer-initiated aggressive social interactions were more characteristic of REM than NREM, and dreamer-initiated friendliness was more characteristic of NREM than REM reports. Both REM and NREM dreams therefore may function to simulate opposing types of social interactions, with the REM state specializing in simulation of aggressive interactions and the NREM state specializing in simulation of friendly interactions. We close our review with a summary of evidence that dream content variables significantly predict daytime mood and social interactions.
Divergence of primitive sleep into REM and NREM states is thought to have occurred in the nocturnal Triassic ancestors of mammals as a natural accompaniment of the evolution of warm-bloodedness. As ambient temperatures during twilight portions of primitive sleep traversed these evolving ancestors' core temperature, mechanisms of thermoregulatory control that employ muscle contractions became superfluous. The resulting loss of need for such contractions during twilight sleep led to muscle atonia. With muscle tone absent, selection favored the persistence of the fast waves of nocturnal activity during twilight sleep. Stimulations by these waves reinforce motor circuits at the increasing temperatures of evolving warm-bloodedness without leading to sleep-disturbing muscle contractions. By these and related interlinked adaptations, twilight sleep evolved into REM sleep. The daytime period of sleep became NREM sleep. The evolution of NREM and REM sleep following this scenario has implications for sleep's maintenance processes for long-term memories. During NREM sleep, there is an unsynchronized, uncoordinated stimulation and reinforcement of individual distributed component circuits of consolidated memories by slow wave potentials, a process termed 'uncoordinated reinforcement'. The corresponding process during REM sleep is the coordinated stimulation and reinforcement of these circuits by fast wave potentials. This action temporally binds the individual component circuit outputs into fully formed memories, a process termed 'coordinated reinforcement'. Sequential uncoordinated and coordinated reinforcement, that is, NREM followed by REM sleep, emerges as the most effective mechanism of long-term memory maintenance in vertebrates. With the evolution of this two-stage mechanism of long-term memory maintenance, it became adaptive to partition sleep into several NREM-REM cycles, thereby achieving a more lengthy application of the cooperative sequential actions.
Participants playing the computer game Tetris reported intrusive, stereotypical, visual images of the game at sleep onset.
Three amnesic patients with extensive bilateral medial temporal lobe damage produced similar hypnagogic reports despite being
unable to recall playing the game, suggesting that such imagery may arise without important contribution from the declarative
memory system. In addition, control participants reported images from previously played versions of the game, demonstrating
that remote memories can influence the images from recent waking experience.
Long-term memory formation consists of multiple phases. A new memory is initially labile and sensitive to disruption by a variety of interfering events or agents. To become stable, this new memory undergoes a process known as consolidation, which, in the case of declarative memories, occurs within the medial temporal lobes and requires gene expression. When recalled, memories re-enter a new phase of vulnerability and seem to require a reconsolidation process in order to be maintained. Here we show that consolidation but not reconsolidation of inhibitory avoidance memory requires the expression of the transcription factor CCAAT enhancer binding protein (C/EBP) in the hippocampus. Furthermore, in the same region, de novo protein synthesis is not essential for memory reconsolidation. C/EBP is an evolutionarily conserved genetic marker that has a selective role in the consolidation of new but not reactivated memories in the hippocampus.
Discoveries in three distinct areas of dream research make it possible to suggest the outlines of a new neurocognitive theory of dreaming. The first relevant findings come from assessments of patients with brain injuries, which show that lesions in different areas have differential effects on dreaming and thereby imply the contours of the neural network necessary for dreaming. The second set of results comes from work with children ages 3–15 in the sleep laboratory, which reveals that only 20–30% of REM period awakenings lead to dream reports up to age 9 and that the dreams of children under age 5 are bland and static in content. The third set of findings comes from a rigorous system of content analysis, which demonstrates the repetitive nature of much dream content and that dream content in general is continuous with waking conceptions and emotional preoccupations. Based on these findings, dreaming is best understood as a developmental cognitive achievement that depends upon the maturation and maintenance of a specific network of forebrain structures. The output of this neural network for dreaming is guided by a continuity principle linked to current personal concerns on the one hand and a repetition principle rooted in past emotional preoccupations on the other.
Consciousness is now considered a primary function and activity of the brain itself. If so, consciousness is simply the brain's interpretation and integration of all the information made available to it at any given time. On the assumption that the brain is active across all states of being (wakefulness, REM sleep, and NREM sleep), this article proposes that dreaming and hallucinations represent variations on the same theme. Under usual circumstances during wakefulness, the brain ignores internally generated activity and attends to environmental sensory stimulation. During sleep, dreaming occurs because the brain attends to endogenously generated activity. In unusual settings, such as sleep-deprivation, sensory deprivation, or medication or drug ingestion, the brain attends to exogenous and endogenous activities simultaneously, resulting in hallucinations, or wakeful dreaming. This concept is supported by numerous neurologic conditions and syndromes that are associated with hallucinations.
Results from recent studies of retrograde amnesia following damage to the hippocampal complex of human and non-human subjects have shown that retrograde amnesia is extensive and can encompass much of a subject's lifetime; the degree of loss may depend upon the type of memory assessed. These and other findings suggest that the hippocampal formation and related structures are involved in certain forms of memory (e.g. autobiographical episodic and spatial memory) for as long as they exist and contribute to the transformation and stabilization of other forms of memory stored elsewhere in the brain.
Damage to the hippocampal system disrupts recent memory but leaves remote memory intact. The account presented here suggests that memories are first stored via synaptic changes in the hippocampal system, that these changes support reinstatement of recent memories in the neocortex, that neocortical synapses change a little on each reinstatement, and that remote memory is based on accumulated neocortical changes. Models that learn via changes to connections help explain this organization. These models discover the structure in ensembles of items if learning of each item is gradual and interleaved with learning about other items. This suggests that the neocortex learns slowly to discover the structure in ensembles of experiences. The hippocampal system permits rapid learning of new items without disrupting this structure, and reinstatement of new memories interleaves them with others to integrate them into structured neocortical memory systems.
Magnetic recording from five normal human adults demonstrates large 40-Hz coherent magnetic activity in the awake and in rapid-eye-movement (REM) sleep states that is very reduced during delta sleep (deep sleep characterized by delta waves in the electroencephalogram). This 40-Hz magnetic oscillation has been shown to be reset by sensory stimuli in the awake state. Such resetting is not observed during REM or delta sleep. The 40 Hz in REM sleep is characterized, as is that in the awake state, by a fronto-occipital phase shift over the head. This phase shift has a maximum duration of approximately 12-13 msec. Because 40-Hz oscillation is seen in wakefulness and in dreaming, we propose it to be a correlate of cognition, probably resultant from coherent 40-Hz resonance between thalamocortical-specific and nonspecific loops. Moreover, we proposed that the specific loops give the content of cognition, and a nonspecific loop gives the temporal binding required for the unity of cognitive experience.
In gross anatomical terms, the hippocampal archicortex can be conceived as an "appendage' of the large neocortex. In contrast to neocortical areas, the main output targets of the hippocampus are the same as its main inputs (i.e., the entorhinal cortex). Highly processed information about the external world (the content) reaches the hippocampus via the entorhinal cortex, whereas information about the "internal world' (the context) is conveyed by the subcortical inputs. Removal of the context makes the content illegible, as demonstrated by the observation that the behavioral impairment following surgical removal of hippocampopetal subcortical inputs is as devastating as removing the hippocampus itself. From its strategic anatomical position and input-output connections, it may be suggested that the main function of the hippocampal formation is to modify its inputs by feeding back a processed "reafferent copy' to the neocortex. I hypothesize that neocortico-hippocampal transfer of information and the modification process in neocortical circuitries by the hippocampal output take place in a temporally discontinuous manner and might be delayed by minutes, hours, or days. Acquisition of information may happen very fast during the activated state of the hippocampus associated with theta/gamma oscillations. Intrahippocampal consolidation and the hippocampal-neocortical transfer of the stored representations, on the other hand, is protracted and carried by discrete quanta of cooperative neuronal bursts during slow wave sleep.
Human actions require integration of past experiences, ongoing percepts and future concepts. To adapt behavior to reality, the brain must identify mental representations of current relevance. Occasional amnesic subjects act according to invented stories ('spontaneous confabulations'), disregarding present reality. We used repeated runs of a continuous recognition task to measure the ability to distinguish currently relevant from previously encountered but currently irrelevant information. Spontaneous confabulators detected target items as accurately as nonconfabulating amnesics, but increasingly failed to suppress false-positive responses, confusing presentation in previous runs with presentation in the current run. Lesions involved the anterior limbic system: medial orbitofrontal cortex, basal forebrain, amygdala and perirhinal cortex or medial hypothalamus. We suggest that the anterior limbic system represents 'now' in human thinking by suppressing currently irrelevant mental associations.
The relation between the activity of a single neocortical neuron and the dynamics of the network in which it is embedded was
explored by single-unit recordings and real-time optical imaging. The firing rate of a spontaneously active single neuron
strongly depends on the instantaneous spatial pattern of ongoing population activity in a large cortical area. Very similar
spatial patterns of population activity were observed both when the neuron fired spontaneously and when it was driven by its
optimal stimulus. The evoked patterns could be used to reconstruct the spontaneous activity of single neurons.
The memory consolidation hypothesis proposed 100 years ago by Müller and Pilzecker continues to guide memory research. The
hypothesis that new memories consolidate slowly over time has stimulated studies revealing the hormonal and neural influences
regulating memory consolidation, as well as molecular and cellular mechanisms. This review examines the progress made over
the century in understanding the time-dependent processes that create our lasting memories.
A permanently existing "idea" which makes its appearance before the footlights of consciousness at periodical intervals is as mythological an entity as the Jack of Spades.
During active behavior, patterns of hippocampal and neocortical neuronal activity reflect ongoing inputs and their contexts. Recent neurophysiological investigations have shown that during 'off-line' periods, traces of these experiences are spontaneously reactivated in both structures. Although the functional importance of this phenomenon remains to be demonstrated, it does provide clues about the nature and mechanisms of memory retrieval and consolidation.
Most neurons receive thousands of synaptic inputs onto widely spread dendrites. Because of dendritic filtering, distant synapses should have less efficacy than proximal ones. To investigate this, we characterized the amplitude and kinetics of excitatory synaptic input across the apical dendrites of CA1 pyramidal neurons using dual whole-cell recordings. We found that dendritic EPSP amplitude increases with distance from the soma, counterbalancing the filtering effects of the dendrites and reducing the location dependence of somatic EPSP amplitude. Dendritic current injections and a multi-compartmental computer model demonstrated that dendritic membrane properties have only a minor role in elevating the local EPSP. Instead a progressive increase in synaptic conductance seems to be primarily responsible for normalizing the amplitudes of individual inputs.
In conclusion, the temporal correlation hypothesis re- mains an attractive theoretical framework for investigating the neural basis of perceptual grouping. The experi- ments I have proposed provide one way to test several of the key predictions of this theory, but these studies are still correlative in nature. A true test of the predictions would be one in which a causal link could be established between synchronous activity and perception. Recent experiments in the insect olfactory system demonstrate that tests of this sort can be accomplished in simpler nervous systems (Laurent, 1996; MacLeod and Laurent, 1996; Wehr and Laurent, 1996; Stopfer et al., 1997). A similar experiment would clearly be difficult to achieve in the primate visual system. Any manipulation that might perturb the patterns of synchronous firing would be likely to influence the overall distribution of activity as well. Consequently, a rigorous test of the correlation hypothesis may ultimately have to rely on a combination of theoretical and experimental evidence obtained from a variety of studies.
The hippocampal CA1 region is crucial for converting new memories into long-term memories, a process believed to continue for week(s) after initial learning. By developing an inducible, reversible, and CA1-specific knockout technique, we could switchN-methyl-d-aspartate (NMDA) receptor function off or on in CA1 during the consolidation period. Our data indicate that memory consolidation depends on the reactivation of the NMDA receptor, possibly to reinforce site-specific synaptic modifications to consolidate memory traces. Such a synaptic reinforcement process may also serve as a cellular means by which the new memory is transferred from the hippocampus to the cortex for permanent storage.
Paradoxical sleep (PS), in which periods with (phasic) and without (tonic) rapid eye movements are intermingled, is hypothesized to be related to cognitive processing and dreaming. Based on polysomnographic data from 12 healthy subjects, this study focuses on the spectral differentiation between phasic and tonic periods. Phasic PS periods exhibited decreased theta and alpha power in the posterior brain areas suggesting the interference of visual processing related to dream imagery. Phasic PS periods were also characterized by a shift from beta to gamma activity in frontal, central and occipital areas reflecting specific phasic related activation. Together, these findings bring new evidence for the existence of visual imagery and cognitive processing during phasic PS.
Following the original description of an ascending reticular activating system located in the brainstem core, the chemical codes of several cellular aggregates with widespread projections to the thalamus and cerebral cortex have been identified by combining axonally transported tracers with immunocytochemistry, the state-dependent activities of brainstem cholinergic neurons with antidromically identified thalamic projections have been investigated in behaving animals, and the actions of generalized modulatory systems on postsynaptic thalamic and cortical targets have been explored intracellularlyin vivoandin vitro. In this concluding article on brain neuromodulatory systems I place emphasis on(a)fast (20–40 Hz) spontaneous rhythms of electrical activity that are synchronous in intracortical as well as corticothalamic networks and represent a major component of activated electrical patterns during brain arousal; the subthreshold depolarizing oscillations may bias neurons to respond synchronously within this frequency range when relevant signals reach the forebrain;(b)the converging and/or competitive effects of various activating systems; and(c)the similarities between the actions of ascending/descending glutamatergic activating projections and those of other (cholinergic and monoaminergic) modulatory systems.
Discusses the function, the instrumental value to the individual, and necessity of dreaming. (PsycINFO Database Record (c) 2012 APA, all rights reserved)
The difference between Sleep Stages 1 REM (rapid eye movement) and NREM (non REM) in reported dreaming is compared to several word frequency measures of characteristics of sleep mentation reports. Total Recall Frequency (total word frequency minus pauses, fillers, corrections, repetitions and commentary) discriminated REM from NREM with approximately the same strength as did global ratings of Dreaming. Although incremental repeated measures multivariate tests showed that each contributed some unique variance to the REM/NREM criterion, the unique portions were trivial in size. Frequencies of words that describe speech and visual imagery during sleep accounted for smaller portions of the REM/NREM variance. To the extent that a simple word frequency recall measure accounts for the same variance that such complex measures as dreaming and imagery share with REM/NREM, we may conclude that judges of Dreaming implicitly rely on a dimension similar to the Total Recall Freq. It is proposed that the cognitive difference between REM and NREM is essentially one of attention and memory. Given the high perceptual thresholds of REM sleep, the events attended to and stored in memory are necessarily unrelated to the surrounding environment and therefore differ from waking thought.
Dreaming is a statistically robust cognitive correlate of REM sleep, but all of its formal features may occur in other states of sleep and even in waking, especially during fantasy. In order to test the hypothesis that the brain basis of such cognitive features as dream bizarreness is to be found in REM sleep neurophysiology, it is critical to quantify bizarreness in dreams and other mental states and to analyze the data with respect to both the magnitude and the kind of bizarreness so measured. Any differences in the cognitive dimensions are candidate correlates of REM sleep neurophysiology. Sixty pairs of home-based dream and fantasy reports were collected from 12 subjects and scored for bizarreness using a two-stage scoring system adapted from Hobson, Hoffman, Helfand, and Kostner (1987). Our results show that bizarreness was twice as prevalent in dream reports as in wake-state fantasy reports of the same subjects. Further analysis of the reports also showed differences in other features including the number of persona and remoteness of time and place.
The idea that sleep could serve a cognitive function has remained popular since Freud stated that dreams were “not nonsense” but a time to sort out experiences [S. Freud, Letter to Wilhelm Fliess, May 1897, in The Origins of Psychoanalysis — Personal Letters of Sigmund Freud, M. Bonaparte, A. Freud, E. Kris (Eds.), Translated by E. Mosbacher, J. Strachey, Basic Books and Imago Publishing, 1954]. Rapid eye movement (REM) sleep, which is associated with dream reports, is now known to be is important for acquisition of some tasks [A. Karni, D. Tanne, B.S. Rubenstein, J.J.M. Askenasy, D. Sagi, Dependence on REM sleep of overnight improvement of a perceptual skill, Science 265 (1994) 679–682; C. Smith, Sleep states and learning: a review of the animal literature, Biobehav. Rev. 9 (1985) 157–168]; although why this is so remains obscure. It has been proposed that memories may be consolidated during REM sleep or that forgetting of unnecessary material occurs in this state [F. Crick, G. Mitchison, The function of dream sleep, Nature 304 (1983) 111-114; D. Marr, Simple memory: a theory for archicortex, Philos. Trans. R. Soc. B. 262 (1971) 23–81]. We studied the firing of multiple single neurons in the hippocampus, a structure that is important for episodic memory, during familiar and novel experiences and in subsequent REM sleep. Cells active in familiar places during waking exhibited a reversal of firing phase relative to local theta oscillations in REM sleep. Because firing-phase can influence whether synapses are strengthened or weakened [C. Holscher, R. Anwyl, M.J. Rowan, Stimulation on the positive phase of hippocampal theta rhythm induces long-term potentiation that can be depotentiated by stimulation on the negative phase in area CA1 in vivo, J. Neurosci. 15 (1977) 6470–6477; P.T. Huerta, J.E. Lisman, Bidirectional synaptic plasticity induced by a single burst during cholinergic theta oscillation in CA1 in vitro, Neuron 15 (1995) 1053–1063; C. Pavlides, Y.J. Greenstein, M. Grudman, J. Winson, Long-term potentiation in the dentate gyrus is induced preferentially on the positive phase of theta-rhythm, Brain Res. 439 (1988) 383–387] this experience-dependent phase shift, which developed progressively over multiple sessions in the environment, is consistent with the hypothesis that circuits may be restructured during REM sleep by selectively strengthening recently acquired memories and weakening older ones.
Behavioral studies of memory and learning in both humans and animals support a role for sleep in the consolidation and integration of memories. Physiological studies of hippocampal and cortical activity as well as of brainstem neuromodulatory systems demonstrate the state-dependence of communication both between and within the neocortex and hippocampus. These findings are consonant with observed cognition during sleep and immediately following awakening.
There is now a substantial body of data to suggest a relationship between sleep states, particularly paradoxical sleep (PS) or rapid eye movement (REM) sleep, and learning. In animal studies, PS increases have been observed following acquisition in formal tasks and following exposure to enriched environments (EE). Further, PS deprivation at certain post-training times is known to impair memory for recently acquired tasks. PS deprivation following EE exposure has been reported to impair the neural changes normally observed. It is argued that the prolonged PS increases observed following either formal training or EE exposure reflect the same kinds of neural change. It is proposed that accelerated neural plasticity takes place during elevated post-training PS and is especially vulnerable to disruption at specific post-training time periods called PS windows. Further, it is proposed that similar processes take place in the post-training sleep of humans.
Recent PET imaging and brain lesion studies in humans are integrated with new basic research findings at the cellular level in animals to explain how the formal cognitive features of dreaming may be the combined product of a shift in neuromodulatory balance of the brain and a related redistribution of regional blood flow. The human PET data indicate a preferential activation in REM of the pontine brain stem and of limbic and paralimbic cortical structures involved in mediating emotion and a corresponding deactivation of dorsolateral prefrontal cortical structures involved in the executive and mnemonic aspects of cognition. The pontine brainstem mechanisms controlling the neuromodulatory balance of the brain in rats and cats include noradrenergic and serotonergic influences which enhance waking and impede REM via anticholinergic mechanisms and cholinergic mechanisms which are essential to REM sleep and only come into full play when the serotonergic and noradrenergic systems are inhibited. In REM, the brain thus becomes activated but processes its internally generated data in a manner quite different from that of waking.
The percentage of dreams with day residue that could be identified by the dreamer, without free associating to the dream, was observed for a sample of 44 men and 44 women college students. The men identified day residue in 46.6% of their dreams and the women identified day residue in 48.9% of their dreams. The results were discussed in the context of Freud's idea that, while every dream likely has day residue, only some dreams have residue that can be identified without first free associating to the dream.
Following a set of studies concerning the intrinsic electrophysiology of mammalian central neurons in relation to global brain function, we reach the following conclusions: (i) the main difference between wakefulness and paradoxical sleep lies in the weight given to sensory afferents in cognitive images; (ii) otherwise, wakefulness and paradoxical sleep are fundamentally equivalent brain states probably subserved by an intrinsic thalamo-cortical loop. From this assumption, we conclude that wakefulness is an intrinsic functional realm, modulated by sensory parameters. In support of this hypothesis, we review morphological studies of the thalamocortical system, which indicate that only a minor part of its connectivity is devoted to the transfer of direct sensory input. Rather, most of the connectivity is geared to the generation of internal functional modes, which may, in principle, operate in the presence or absence of sensory activation. These considerations lead us to challenge the traditional Jamesian view of brain function according to which consciousness is generated as an exclusive by-product of sensory input. Instead, we argue that consciousness is fundamentally a closed-loop property, in which the ability of cells to be intrinsically active plays a central role. We further discuss the importance of spatial and temporal mapping in the elaboration of cognitive and perceptual constructs.
Experiential phenomena that occur in temporal lobe seizures and can be reproduced by electrical stimulation of temporal lobe structures typically encompass perceptual, mnemonic and affective features, either in combination or in isolation, which commonly relate to the patient's individual past experience. These phenomena raise interesting questions concerning brain mechanisms involved in human psychophysiology. The anatomical substrates for the evocation of these phenomena are widely distributed within the temporal lobe and include temporal isocortex and limbic structures (amygdala, hippocampus and parahippocampal gyrus). Arguments are presented which indicate that experiential phenomena are positive expressions of temporal lobe and limbic function and do not result from its ictal paralysis. Recent concepts of parallel distributed processing (Rumelhart and McClelland, 1986) and the importance of parallel distributed cortical networks for higher cognitive functions (Goldman-Rakic, 1988a, b) provide a theoretical framework on which a hypothesis explaining experiential phenomena can be based. In conformity with these concepts the hypothesis assumes that temporal lobe epileptic discharge or electrical stimulation of temporal lobe structures can induce the elaboration of patterns of excitation and inhibition in widely distributed neuronal networks, some of which are capable of forming a specific matrix representing the substrate of a given experience. Neuronal networks engaged in parallel distributed processing (1) have the capacity to recreate the totality of a given experience when only a fragment of the network is activated, and (2) they tolerate a great deal of degradation by random inactivation of its components or by interference through random noise without serious loss of information content. These features are compatible with the assumption that localized epileptic neuronal discharge or electrical stimulation involving some temporal lobe structures could create a matrix representing features of individual experience of the kind activated in the course of temporal lobe seizures. Such an experience could, up to a certain limit, resist the degrading influence of mounting noise which inevitably must attend seizure discharge.
In recent years dreaming has been characterized as an information-processing activity that functions adaptively to match new experience with representations of past events already stored in long-term memory. Nine patients who reported dreams in psychotherapy were asked expressly if the dream imagery recalled a specific event from early in their lives. Of 50 consecutively reported dreams, 46 were associated with early events whose imagery appeared in the dream. When questioning about the past was omitted in a later series of 34 dreams, the same patients spontaneously recalled early events represented in the dream imagery only 13 times.
Phylogenetic studies in placental and marsupial mammals have demonstrated three major correlates of increased REM sleep time across these species. These are high amounts of non-REM sleep time, safe sleep conditions and immaturity at birth. While these variables explain approximately 30% of the variance in REM sleep time across these orders, these relations are violated when animals other than placentals are included. Birds are small, many have safe sleeping situations and are certainly immature at birth, yet they have less REM sleep than the vast majority of mammals. The echidna is immature at birth, has high amounts of non-REM sleep and safe sleeping conditions, yet has been reported to have no REM sleep. Our recent studies in the echidna indicate that REM and non-REM sleep did not evolve sequentially, but rather evolved as a differentiation of a primitive state which held the seeds of both sleep states. The echidna sleeps with an activated brainstem and EEG synchronized forebrain. Future studies of sleep phylogeny need to compare the behavior of key neuronal groups across the sleep cycle, since these results indicate that EEG variables and sleep state durations may given an inadequate picture of the nature of brain activity during sleep.
Simultaneous recordings were made from large ensembles of hippocampal "place cells" in three rats during spatial behavioral
tasks and in slow-wave sleep preceding and following these behaviors. Cells that fired together when the animal occupied particular
locations in the environment exhibited an increased tendency to fire together during subsequent sleep, in comparison to sleep
episodes preceding the behavioral tasks. Cells that were inactive during behavior, or that were active but had non-overlapping
spatial firing, did not show this increase. This effect, which declined gradually during each post-behavior sleep session,
may result from synaptic modification during waking experience. Information acquired during active behavior is thus re-expressed
in hippocampal circuits during sleep, as postulated by some theories of memory consolidation.
Dissociations between perception and awareness of perception are of interest for what they can tell us about the neural correlates of awareness. Recent research in this field has focussed on perception-awareness dissociations in the syndromes of blindsight, covert recognition in two kinds of visual agnosia, and visual neglect.
20 subjects viewed an emotionally arousing video and then recorded their dreams at home for seven nights. Dreams were subsequently rated for the likelihood that some aspect of the video had been incorporated. For subjects who showed strong evidence of incorporation, mean likelihood of incorporation ratings followed a U-shaped pattern, with significantly higher scores on Nights 1, 6, and 7 than on Night 4. The similarity of this temporal pattern with REM sleep patterns observed in rats exposed to various learning experiences is noted, and the role of the hippocampus as a possible neural mechanism for delayed incorporations is discussed.
The regulation of synaptic signal transduction is of central importance to our understanding of normal and abnormal nervous system function. One mechanism by which signal transduction can be affected is the modification of cellular sensitivity by alterations of transmembrane receptor properties. For G-protein coupled receptors, protein phosphorylation is intimately involved in many stages of receptor regulation. This appears to be true for ionotropic receptors as well. Evidence of a role for protein kinase and protein phosphatase activity in the multi-staged ionotropic receptor regulation cascade is presented and a comparison to G-protein coupled receptor regulation is considered.
Mentation reports collected from sleep onset, Stage 2 and REM Stage awakenings, in the first part and in the second part of the night were analyzed both with systematic psycholinguistic and global measures. Results confirm the relationship between activation and the length of sleep mentation report shown by Antrobus. Length of the report increases with sleep time, but time does not modulate qualitative inter-stage differences. By partialling out the length of the report, many inter-stage differences disappeared; however significant differences remain in the global measure of bizarreness and in the psycholinguistic measure of visual imagery. These results cannot be explained entirely by differences in attention and memory and point to more basic differences in mental activity.
Repeated stimulation of hippocampal neurons can induce an immediate and prolonged increase in synaptic strength that is called long-term potentiation (LTP)-the primary cellular model of memory in the mammalian brain. An early phase of LTP (lasting less than three hours) can be dissociated from late-phase LTP by using inhibitors of transcription and translation, Because protein synthesis occurs mainly in the cell body, whereas LTP is input-specific, the question arises of how the synapse specificity of late LTP is achieved without elaborate intracellular protein trafficking. We propose that LTP initiates the creation of a short-lasting protein-synthesis-independent 'synaptic tag' at the potentiated synapse which sequesters the relevant protein(s) to establish late LTP. In support of this idea, we now show that weak tetanic stimulation, which ordinarily leads only to early LTP, or repeated tetanization in the presence of protein-synthesis inhibitors, each results in protein-synthesis-dependent late LTP, provided repeated tetanization has already been applied at another input to the same population of neurons. The synaptic tag decays in less than three hours. These findings indicate that the persistence of LTP depends not only on local events during its induction, but also on the prior activity of the neuron.
The origin of both sleep and memory appears to be closely associated with the evolution of mechanisms of enhancement and maintenance of synaptic efficacy. The development of activity-dependent synaptic plasticity apparently was the first evolutionary adaptation of nervous systems beyond a capacity to respond to environmental stimuli by mere reflexive actions. After the origin of activity-dependent synaptic plasticity, whereby single activations of synapses led to short-term efficacy enhancement, lengthy maintenance of enhancements probably was achieved by repetitive activations ("dynamic stabilization"). One source of selective pressure for the evolutionary origin of neurons and neural circuits with oscillatory firing capacities may have been a need for repetitive spontaneous activations to maintain synaptic efficacy in circuits that were in infrequent use. This process is referred to as "non-utilitarian" dynamic stabilization. Dynamic stabilization of synapses in "simple" invertebrates occurs primarily through frequent use. In complex, locomoting forms, it probably occurs through both frequent use and non-utilitarian activations during restful waking. With the evolution of increasing repertories and complexities of behavioral and sensory capabilities--with vision usually being the vastly pre-eminent sense brain complexity increased markedly. Accompanying the greater complexity, needs for storage and maintenance of hereditary and experiential information (memories) increased greatly. It is suggested that these increases led to conflicts between sensory input processing during restful waking and concomitant non-utilitarian dynamic stabilization of infrequently used memory circuits. The selective pressure for the origin of primitive sleep may have been a resulting need to achieve greater depression of central processing of sensory inputs largely complex visual information than occurs during restful waking. The electrical activities of the brain during sleep (aside from those that subserve autonomic activities) may function largely to maintain sleep and to dynamically stabilize infrequently used circuitry encoding memories. Sleep may not have been the only evolutionary adaptation to conflicts between dynamic stabilization and sensory input processing. In some ectothermic vertebrates, sleep may have been postponed or rendered unnecessary by a more readily effected means of resolution of the conflicts, namely, extensive retinal processing of visual information during restful waking. By this means, processing of visual information in central regions of the brain may have been maintained at a sufficiently low level to allow adequate concomitant dynamic stabilization. As endothermy evolved, the skeletal muscle hypotonia of primitive sleep may have become insufficient to prevent sleep-disrupting skeletal muscle contractions during non-utilitarian dynamic stabilization of motor circuitry at the accompanying higher body temperatures and metabolic rates. Selection against such disruption during dynamic stabilization of motor circuitry may have led to the inhibition of skeletal muscle tone during a portion of primitive sleep, the portion designated as rapid-eye-movement sleep. Many marine mammals that are active almost continuously engage only in unihemispheric non-rapid-eye-movement sleep. They apparently do not require rapid-eye-movement sleep and accompanying non-utilitarian dynamic stabilization of motor circuitry, because this circuitry is in virtually continuous use. Studies of hibernation by arctic ground squirrels suggest that each hour of sleep may stabilize brain synapses for as long as 4 h. Phasic irregularities in heart and respiratory rates during rapid-eye-movement sleep may be a consequence of superposition of dynamic stabilization of motor circuitry on the rhythmic autonomic control mechanisms. Some information encoded in circuitry being dynamically stabilized during sleep achieves unconscious awareness in authentic and var
The study of sleep and dreams has enjoyed a major breakthrough with recent findings from brain imaging studies in humans. Several independent groups have shown global deactivation of the brain during non rapid eye movement sleep and a regionally selective reactivation during rapid eye movement sleep. These results are complemented by new brain lesion and electrophysiological recording data to give a detailed picture of the brain dynamics of changes in conscious state.
Sensory information undergoes extensive associative elaboration and attentional modulation as it becomes incorporated into the texture of cognition. This process occurs along a core synaptic hierarchy which includes the primary sensory, upstream unimodal, downstream unimodal, heteromodal, paralimbic and limbic zones of the cerebral cortex. Connections from one zone to another are reciprocal and allow higher synaptic levels to exert a feedback (top-down) influence upon earlier levels of processing. Each cortical area provides a nexus for the convergence of afferents and divergence of efferents. The resultant synaptic organization supports parallel as well as serial processing, and allows each sensory event to initiate multiple cognitive and behavioural outcomes. Upstream sectors of unimodal association areas encode basic features of sensation such as colour, motion, form and pitch. More complex contents of sensory experience such as objects, faces, word-forms, spatial locations and sound sequences become encoded within downstream sectors of unimodal areas by groups of coarsely tuned neurons. The highest synaptic levels of sensory-fugal processing are occupied by heteromodal, paralimbic and limbic cortices, collectively known as transmodal areas. The unique role of these areas is to bind multiple unimodal and other transmodal areas into distributed but integrated multimodal representations. Transmodal areas in the midtemporal cortex, Wernicke's area, the hippocampal-entorhinal complex and the posterior parietal cortex provide critical gateways for transforming perception into recognition, word-forms into meaning, scenes and events into experiences, and spatial locations into targets for exploration. All cognitive processes arise from analogous associative transformations of similar sets of sensory inputs. The differences in the resultant cognitive operation are determined by the anatomical and physiological properties of the transmodal node that acts as the critical gateway for the dominant transformation. Interconnected sets of transmodal nodes provide anatomical and computational epicentres for large-scale neurocognitive networks. In keeping with the principles of selectively distributed processing, each epicentre of a large-scale network displays a relative specialization for a specific behavioural component of its principal neurospychological domain. The destruction of transmodal epicentres causes global impairments such as multimodal anomia, neglect and amnesia, whereas their selective disconnection from relevant unimodal areas elicits modality-specific impairments such as prosopagnosia, pure word blindness and category-specific anomias. The human brain contains at least five anatomically distinct networks. The network for spatial awareness is based on transmodal epicentres in the posterior parietal cortex and the frontal eye fields; the language network on epicentres in Wernicke's and Broca's areas; the explicit memory/emotion network on epicentres in the hippocampal-entorhinal complex and the amygdala; the face-object recognition network on epicentres in the midtemporal and temporopolar cortices; and the working memory-executive function network on epicentres in the lateral prefrontal cortex and perhaps the posterior parietal cortex. Individual sensory modalities give rise to streams of processing directed to transmodal nodes belonging to each of these networks. The fidelity of sensory channels is actively protected through approximately four synaptic levels of sensory-fugal processing. The modality-specific cortices at these four synaptic levels encode the most veridical representations of experience. Attentional, motivational and emotional modulations, including those related to working memory, novelty-seeking and mental imagery, become increasingly more pronounced within downstream components of unimodal areas, where they help to create a highly edited subjective version of the world. (ABSTRACT TRUNCATED)
Evidence is presented that EEG oscillations in the alpha and theta band reflect cognitive and memory performance in particular. Good performance is related to two types of EEG phenomena (i) a tonic increase in alpha but a decrease in theta power, and (ii) a large phasic (event-related) decrease in alpha but increase in theta, depending on the type of memory demands. Because alpha frequency shows large interindividual differences which are related to age and memory performance, this double dissociation between alpha vs. theta and tonic vs. phasic changes can be observed only if fixed frequency bands are abandoned. It is suggested to adjust the frequency windows of alpha and theta for each subject by using individual alpha frequency as an anchor point. Based on this procedure, a consistent interpretation of a variety of findings is made possible. As an example, in a similar way as brain volume does, upper alpha power increases (but theta power decreases) from early childhood to adulthood, whereas the opposite holds true for the late part of the lifespan. Alpha power is lowered and theta power enhanced in subjects with a variety of different neurological disorders. Furthermore, after sustained wakefulness and during the transition from waking to sleeping when the ability to respond to external stimuli ceases, upper alpha power decreases, whereas theta increases. Event-related changes indicate that the extent of upper alpha desynchronization is positively correlated with (semantic) long-term memory performance, whereas theta synchronization is positively correlated with the ability to encode new information. The reviewed findings are interpreted on the basis of brain oscillations. It is suggested that the encoding of new information is reflected by theta oscillations in hippocampo-cortical feedback loops, whereas search and retrieval processes in (semantic) long-term memory are reflected by upper alpha oscillations in thalamo-cortical feedback loops.
Brain circuits for infrequently employed memories are reinforced largely during sleep by self-induced, electrical slow-waves, a process referred to as "dynamic stabilization" (DS). The essence of waking brain function in the absence of volitional activity is sensory input processing, an enormous amount of which is visual. These two functions: circuit reinforcement by DS and sensory information processing come into conflict when both occur at a high level, a conflict that may have been the selective pressure for sleep's origin. As brain waves are absent at the low temperatures of deep torpor, essential circuitry of hibernating small mammals would lose its competence if the animals did not warm up periodically to temperatures allowing sleep and circuit reinforcement. Blind, cave-dwelling vertebrates require no sleep because their sensory processing does not interfere with DS. Nor does such interference arise in continuously-swimming fishes, whose need to process visual information is reduced greatly by life in visually relatively featureless, pelagic habitats, and by schooling. Dreams are believed to have their origin in DS of memory circuits. They are thought to have illusory content when the circuits are partially degraded (incompetent), with synaptic efficacies weakened through infrequent use. Partially degraded circuits arise normally in the course of synaptic efficacy decay, or pathologically through abnormal regimens of DS. Organic delirium may result from breakdown of normal regimens of DS of circuitry during sleep, leaving many circuits incompetent. Activation of incompetent circuits during wakefulness apparently produces delirium and hallucinations. Some epileptic seizures may be induced by abnormal regimens of DS of motor circuitry. Regimens of remedial DS during seizures induced by electroconvulsive therapy (ECT) apparently produce temporary remission of delirium by restoring functional or 'dedicated' synaptic efficacies in incompetent circuitry. Sparing of sensory circuitry in fatal familial insomnia seemingly owes to supernormal circuit use in the virtual absence of sleep. ECT shocks and cardioverter defibrillation may have analogous remedial influences.
Quantitative fluorescence imaging was used to study the regulation of acetylcholine receptor (AChR) number and density at
neuromuscular junctions in living adult mice. At fully functional synapses, AChRs have a half-life of about 14 days. However,
2 hours after neurotransmission was blocked, the half-life of the AChRs was now less than a day; the rate was 25 times faster
than before. Most of the lost receptors were not quickly replaced. Direct muscle stimulation or restoration of synaptic transmission
inhibited this process. AChRs that were removed from nonfunctional synapses resided for hours in the perijunctional membrane
before being locally internalized. Dispersed AChRs could also reaggregate at the junction once neurotransmission was restored.
The rapid and reversible alterations in AChR density at the neuromuscular junction in vivo parallel changes thought to occur
in the central nervous system at synapses undergoing potentiation and depression.
Gamma oscillations, now widely regarded as functionally relevant signals of the brain, illustrate that the concept of event-related oscillations bridges the gap between single neurons and neural assemblies. Taking this concept further, we review experiments showing that oscillatory phenomena such as alpha, theta, or delta responses to events are strongly interwoven with sensory and cognitive functions. This review argues that selectively distributed delta, theta, alpha, and gamma oscillatory systems act as resonant communication networks through large populations of neurons. Thus, oscillatory processes might play a major role in relation with memory and integrative functions. A new 'neurons-brain' doctrine is also proposed to extend the neuron doctrine of Sherrington.
Long-term potentiation (LTP) of synaptic transmission is traditionally elicited by massively synchronous, high-frequency inputs, which rarely occur naturally. Recent in vitro experiments have revealed that both LTP and long-term depression (LTD) can arise by appropriately pairing weak synaptic inputs with action potentials in the postsynaptic cell. This discovery has generated new insights into the conditions under which synaptic modification may occur in pyramidal neurons in vivo. First, it has been shown that the temporal order of the synaptic input and the postsynaptic spike within a narrow temporal window determines whether LTP or LTD is elicited, according to a temporally asymmetric Hebbian learning rule. Second, backpropagating action potentials are able to serve as a global signal for synaptic plasticity in a neuron compared with local associative interactions between synaptic inputs on dendrites. Third, a specific temporal pattern of activity--postsynaptic bursting--accompanies synaptic potentiation in adults.
A hippocampal pyramidal neuron receives more than 104excitatory glutamatergic synapses. Many of these synapses contain the molecular machinery for messenger RNA translation, suggesting
that the protein complement (and thus function) of each synapse can be regulated on the basis of activity. Here, local postsynaptic
protein synthesis, triggered by synaptic activation of metabotropic glutamate receptors, was found to modify synaptic transmission
within minutes.
Dendritic spines compartmentalize calcium, and this could be their main function. We review experimental work on spine calcium dynamics. Calcium influx into spines is mediated by calcium channels and by NMDA and AMPA receptors and is followed by fast diffusional equilibration within the spine head. Calcium decay kinetics are controlled by slower diffusion through the spine neck and by spine calcium pumps. Calcium release occurs in spines, although its role is controversial. Finally, the endogenous calcium buffers in spines remain unknown. Thus, spines are calcium compartments because of their morphologies and local influx and extrusion mechanisms. These studies highlight the richness and heterogeneity of pathways that regulate calcium accumulations in spines and the close relationship between the morphology and function of the spine.
'New' memories are initially labile and sensitive to disruption before being consolidated into stable long-term memories. Much evidence indicates that this consolidation involves the synthesis of new proteins in neurons. The lateral and basal nuclei of the amygdala (LBA) are believed to be a site of memory storage in fear learning. Infusion of the protein synthesis inhibitor anisomycin into the LBA shortly after training prevents consolidation of fear memories. Here we show that consolidated fear memories, when reactivated during retrieval, return to a labile state in which infusion of anisomycin shortly after memory reactivation produces amnesia on later tests, regardless of whether reactivation was performed 1 or 14 days after conditioning. The same treatment with anisomycin, in the absence of memory reactivation, left memory intact. Consistent with a time-limited role for protein synthesis production in consolidation, delay of the infusion until six hours after memory reactivation produced no amnesia. Our data show that consolidated fear memories, when reactivated, return to a labile state that requires de novo protein synthesis for reconsolidation. These findings are not predicted by traditional theories of memory consolidation.
Memory circuits of the brain are activated by self-generated brain waves, primarily during sleep. These activations refresh the efficacies (strengths) of synapses in affected circuits, maintaining the efficacies at the "dedicated" values that support circuit functions. The neural pathologies underlying many mental disorders appear to exert their deleterious influences by inducing abnormalities in brain waves. The abnormal waves, in turn, fail to sustain dedicated synaptic efficacies in memory circuits, leading to mental malfunction. Dreaming is an "unconscious" awareness of circuit reinforcement during sleep, with dream contents being derived from the activated circuits. When synaptic efficacies are degraded, the dreams are illusory.