Barbara E Jones

McGill University | McGill · Department of Neurology and Neurosurgery

The cholinergic neurons in the pontomesencephalic tegmentum have been shown to discharge in association with and promote cortical activation during active or attentive waking (aW) and paradoxical or rapid eye movement sleep (PS or REMS). However, GABA neurons lie intermingled with the cholinergic neurons and may contribute to or oppose this activit...

The principal neurons of the arousal and sleep circuits are comprised by glutamate and GABA neurons, which are distributed within the reticular core of the brain and, through local and distant projections orexin and interactions, regulate cortical activity, and behavior across wake-sleep states. These are in turn modulated by the neuromodulatory sy...

Acetylcholine (ACh) neurons in the pontomesencephalic tegmentum (PMT) are thought to play an important role in promoting cortical activation with waking (W) and paradoxical sleep [PS; or rapid eye movement (REM)], but have yet to be proven to do so by selective stimulation and simultaneous recording of identified ACh neurons. Here, we employed opto...

We have examined whether GABAergic neurons in the mesencephalic reticular formation (RFMes), which are believed to inhibit the neurons in the pons that generate paradoxical sleep (PS or REMS), are submitted to homeostatic regulation under conditions of sleep deprivation (SD) by enforced waking during the day in mice. Using immunofluorescence, we in...

Muscle tone is regulated across sleep-wake states, being maximal in waking, reduced in slow wave sleep (SWS) and absent in paradoxical or REM sleep (PS or REMS). Such changes in tone have been recorded in the masseter muscles and shown to correspond to changes in activity and polarization of the trigeminal motor 5 (Mo5) neurons. The muscle hypotoni...

Electrophysiological recordings indicate that neurons which discharge maximally in association with distinct sleep–wake states are distributed through the brain, albeit in differing proportions. As studied using juxtacellular recording and labeling within the basal forebrain, four functional principal cell types are distinguished as: wake/paradoxic...

Neuronal activity is regulated in a homeostatic manner through changes in inhibitory GABA and excitatory glutamate (Glu) AMPA (A) receptors (GluARs). Using immunofluorescent staining, we examined whether calcium/calmodulin-dependent protein kinase IIα (CaMKIIα)-labeled (+) excitatory neurons in the barrel cortex undergo such homeostatic regulation...

Through application of the latest calcium imaging techniques, a new study shows that pyramidal neurons generally decrease their activity during slow wave sleep and, remarkably, REM sleep, whereas parvalbumin interneurons increase their activity and could thus inhibit particular pyramidal cells during REM sleep.

Characterized by dream-enactment motor manifestations arising from rapid eye movement (REM) sleep, REM sleep behavior disorder (RBD) is frequently encountered in Parkinson’s disease (PD). Yet the specific neurostructural changes associated with RBD in PD patients remain to be revealed by neuroimaging. Here we identified such neurostructural alterat...

Though overlapping in distribution through the hypothalamus, orexin (Orx) and melanin-concentrating hormone (MCH) neurons play opposite roles in the regulation of sleep–wake states. Orx neurons discharge during waking, whereas MCH neurons discharge during sleep. In the present study, we examined in mice whether GABAA and GABAB receptors (Rs) are pr...

Unlabelled: Orexin (Orx) neurons are known to be involved in the promotion and maintenance of waking because they discharge in association with cortical activation and muscle tone during waking and because, in their absence, waking with muscle tone cannot be maintained and narcolepsy with cataplexy ensues. Whether Orx neurons discharge during waki...

Distributed within the laterodorsal tegmental and pedunculopontine tegmental nuclei (LDT and PPT), cholinergic neurons in the pontomesencephalic tegmentum have long been thought to play a critical role in stimulating cortical activation during waking (W) and paradoxical sleep (PS, also called REM sleep), yet also in promoting PS with muscle atonia....

Glossary Basal forebrain: An area of the basal telencephalon where neurons which release acetylcholine (ACh), thus cholinergic, are located and give rise to projections to the cerebral cortex where they stimulate cortical activation during waking and paradoxical (rapid eye m ovement (REM)) sleep. Other neurons in the same area release glutamate or...

Somatostatin (SST) is a neuropeptide with known inhibitory actions in the hypothalamus, where it inhibits release of growth hormone-releasing hormone (GHRH), while also influencing the sleep-wake cycle. Here we investigated in the rat whether SST neurons might additionally release GABA (gamma-aminobutyric acid) or glutamate in different regions and...

Melanin-concentrating hormone (MCH) is synthesized by neurons located in the hypothalamus and projecting to widespread regions of the brain, including the locus coeruleus (LC), through which MCH could modulate sleep-wake states. Yet MCH does not appear to exert direct postsynaptic effects on target neurons, including the noradrenergic LC neurons. P...

This chapter discusses the neurobiology of waking and sleeping. Waking and sleeping are actively generated by neuronal systems distributed through the brainstem and forebrain with different projections, discharge patterns, neurotransmitters, and receptors. Specific ascending systems stimulate cortical activation, characterized by fast, particularly...

We recently demonstrated, in rat brain slices, that the usual excitation by noradrenaline (NA) of hypocretin/orexin (hcrt/orx) neurons was changed to an inhibition following sleep deprivation (SD). Here we describe that in control condition (CC), i.e. following 2 hours of natural sleep in the morning, the α(2)-adrenergic receptor (α(2)-AR) agonist,...

In a previous study we proposed that the depolarized state of the wake-promoting hypocretin/orexin (hcrt/orx) neurons was independent of synaptic inputs as it persisted in tetrodotoxin and low calcium/high magnesium solutions. Here we show first that these cells are hyperpolarized when external sodium is lowered, suggesting that non-selective catio...

Orexin (Orx or hypocretin) is critically important for maintaining wakefulness, since in its absence, narcolepsy with cataplexy occurs. In this role, Orx-containing neurons can exert their influence upon multiple targets through the brain by release of Orx but possibly also by release of other neurotransmitters. Indeed, evidence was previously pres...

The lateral hypothalamus (LH), where wake-active orexin (Orx)-containing neurons are located, has been considered a waking center. Yet, melanin-concentrating hormone (MCH)-containing neurons are codistributed therein with Orx neurons and, in contrast to them, are active during sleep, not waking. In the present study employing juxtacellular recordin...

The acetylcholine-releasing, cholinergic cell groups, located in the pontomesencephalic tegmentum and the basal forebrain, serve through their respective projections into the forebrain and cerebral cortex to promote cortical activation during waking and rapid eye movement sleep.

Whereas basal forebrain (BF) cholinergic neurons are known to participate in processes of cortical activation during wake (W) and paradoxical sleep (PS or P, also called REM sleep), codistributed GABAergic neurons have been thought to participate in processes of cortical deactivation and slow-wave sleep (SWS or S). To learn the roles the GABAergic...

Cholinergic neurons in the pontomesencephalic tegmentum form part of the ascending activating system and are thought to participate in stimulating cortical activation. Yet in the laterodorsal tegmental and pedunculopontine tegmental nuclei (LDT and PPT), they lie intermingled with GABAergic and glutamatergic neurons, which could also modulate corti...

Neurons containing melanin-concentrating hormone (MCH) are codistributed with neurons containing orexin (Orx or hypocretin) in the lateral hypothalamus, a peptide and region known to be critical for maintaining wakefulness. Evidence from knockout and c-Fos studies suggests, however, that the MCH neurons might play a different role than Orx neurons...

Whereas glia were once thought to be passive structural elements in the brain, they have more recently been revealed to be active players in providing metabolic support for and regulating activity of the neurons they surround. Notably, it was discovered that glia can be activated by neurotransmitters released from adjacent excitatory synapses and c...

Noradrenaline (NA)- and serotonin (5-HT)-containing neurons, located in the locus coeruleus (LC) and raphe nuclei of the brain stem, respectively, both discharge selectively during waking and serve to promote waking and prevent REM sleep with muscle atonia. During waking, however, NA and 5-HT neurons are differentially responsive and active in asso...

Acetylcholine (ACh) plays an important role in the promotion of paradoxical sleep (PS) with muscle atonia through the muscarinic-2 receptor (M2R) in the mesopontine tegmentum. Conversely, orexin (Orx or hypocretin) appears to be critical for the maintenance of waking with muscle tone through the orexin-2 (or hypocretin-B) receptor (Orx2R), which is...

Multiple neuronal systems contribute to the promotion and maintenance of the wake state, which is characterized by cortical activation and behavioral arousal. Using predominantly glutamate as a neurotransmitter, neurons within the reticular formation of the brainstem give rise to either ascending projections into the forebrain or descending project...

The present study was undertaken to characterize the pre- and postsynaptic constituents of the basal forebrain (BF) projection to the prefrontal cortex in the rat, and determine whether it includes glutamatergic in addition to established gamma-aminobutyric acid (GABA)ergic and cholinergic elements. BF fibres were labelled by anterograde transport...

As the major brain circadian pacemaker, the suprachiasmatic nucleus (SCN) is known to influence the timing of sleep and waking. We thus investigated here the effect of SCN stimulation on neurons of the ventrolateral preoptic nucleus (VLPO) thought to be involved in promoting sleep. Using an acute in vitro preparation of the rat anterior hypothalamu...

The basal forebrain (BF) cholinergic neurons play an important role in cortical activation and arousal and are active in association with cortical activation of waking and inactive in association with cortical slow wave activity of sleep. In view of findings that GABAA receptors (Rs) and inhibitory transmission undergo dynamic changes as a function...

The basal forebrain (BF) plays an important role in modulating cortical activity and influencing attention, learning and memory. These activities are fulfilled importantly yet not entirely by cholinergic neurons. Noncholinergic neurons also contribute and comprise GABAergic neurons and other possibly glutamatergic neurons. The aim of the present st...

Orexin/hypocretin (Orx) neurons are critical for the maintenance of waking in association with behavioral arousal and postural muscle tone, since with their loss narcolepsy with cataplexy occurs. Given that basal forebrain (BF) neurons project to the hypothalamus and play important diverse roles in sleep/wake states, we sought to determine whether...

The neurons of the lateral hypothalamus that contain hypocretin/orexin (hcrt/orx) are thought to promote arousal through the excitatory action they exert on the multiple areas to which they project within the CNS. We show here that the hcrt/orx peptides can also exert a strong action on the amygdala, a structure known for its implication in emotion...

The importance of the lateral hypothalamus in the regulation of reward and motivation has long been recognized. However, the neuronal network involved in such a hypothalamic regulation of reward remains essentially unknown. Recently, hypocretin-containing neurons, a group of hypothalamic neurons known to be associated with the stability of arousal,...

The basal forebrain (BF) is known to play important roles in cortical activation and sleep, which are likely mediated by chemically differentiated cell groups including cholinergic, gamma-aminobutyric acid (GABA)ergic and other unidentified neurons. One important target of these cells is the lateral hypothalamus (LH), which is critical for arousal...

As established in early studies, the basalo-cortical system serves as an extra-thalamic relay from the brainstem reticular activating system to the cerebral cortex. As Mircea Steriade documented, activating impulses are transmitted through either the nonspecific thalamo-cortical projection system or the basalo-cortical projection system to stimulat...

Multiple arousal systems maintain waking through the actions of chemical neurotransmitters that are released from broadly distributed nerve terminals when the neurons fire. Among these, noradrenaline-, histamine- and orexin-containing neurons fire during waking with behavioral arousal, decrease firing during slow-wave sleep (SWS) and cease firing d...

Although maintained by multiple arousal systems, wakefulness falters if orexin (hypocretin), orexin receptors, or orexin neurons are deficient; narcolepsy results with hypersomnolence or sudden onset of rapid eye movement sleep [or paradoxical sleep (PS)] and loss of muscle tonus. To learn how orexin neurons maintain wakefulness, we recorded neuron...

Though overlapping in distribution within the posterior hypothalamus, neurons containing orexin (Orx) and melanin concentrating hormone (MCH) may play different roles in the regulation of behavioural state. In the present study in rats, we tested whether they express c-Fos differently after total sleep deprivation (SD) vs. sleep recovery (SR). Wher...

It is known that acetylcholine can stimulate activation and promote plasticity in the cerebral cortex, yet it is not known how the cholinergic basal forebrain neurons, which release acetylcholine in the cortex, discharge in relation to natural cortical activity and sleep-wake states. By recording basal forebrain units in association with electroenc...

Hypocretin/orexin (Hcrt/Orx) and melanin concentrating hormone (MCH) are peptides contained in overlapping cell groups of the lateral hypothalamus and commonly involved in regulating sleep-wake states and energy balance, though likely in different ways. To see if these neurons are similarly or differentially modulated by neurotransmitters of the ma...

As evidenced by the narcoleptic syndrome that occurs in mice following knock out of the gene for the peptide hypocretin/orexin (Hcrt/Orx),1 in dogs following knock out of the gene for Hcrt/Orx receptors2 and in humans in association with the loss of Hcrt/Orx peptide and neurons,3, 4 Hcrt/Orx appears to be essential for the maintenance of waking. Th...

Since its electrophysiological identification in the 1950's, the state of REMS or PS has been shown through multiple lines of evidence to be generated by neurons in the oral pontine tegmentum. The perpetration of this paradoxical state that combines cortical activation with the most profound behavioral sleep occurs through interplay between PS-prom...

The hypocretin-orexin (hcrt-orx) neurons are thought to maintain wakefulness because their loss results in narcolepsy. This role may be fulfilled by the excitatory action that the hcrt-orx peptide exerts on multiple brainstem and forebrain systems that, in turn, promote cortical activation. Here, we examined whether hcrt-orx may also exert a postsy...

The basal forebrain has been shown to play an important role in cortical activation of wake and paradoxical sleep (PS), yet has also been posited to play a role in slow wave sleep (SWS). In an effort to determine whether these different roles may be fulfilled by different cell groups, including cholinergic and GABAergic cells, we recorded from 123...

The basal forebrain (BF) contains cholinergic neurons that stimulate cortical activation during waking. In addition, both the BF and adjacent preoptic area (POA) contain neurons that promote sleep. We examined c-Fos expression in cholinergic and GABAergic neurons in the BF and POA to determine whether they are differentially active following sleep...

The basal forebrain constitutes the ventral extra-thalamic relay from the brainstem activating system to the cerebral cortex. Cholinergic neurons form an important contingent of this relay, yet represent only a portion of the cortically projecting and other basal forebrain neurons, which include GABAergic neurons. By recording, labeling and identif...

According to multiple lines of evidence, neurons in the ventrolateral preoptic area (VLPO) that contain GABA promote sleep by inhibiting neurons of the arousal systems. Reciprocally, transmitters used by these systems, including acetylcholine (ACh) and noradrenaline (NA), exert an inhibitory action on the VLPO neurons. Because nicotine, an agonist...

The basal forebrain plays an important role in the modulation of cortical activity and sleep-wake states. Yet its role must be multivalent as lesions reportedly diminish cortical fast activity and also cortical slow activity along with slow wave sleep (SWS). Basal forebrain cholinergic vs. GABAergic cell groups could differentially in¯uence these p...