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Within the last four decades, our view of the mature vertebrate brain has changed significantly. Today it is generally accepted that the adult brain is far from being fixed. A number of factors such as stress, adrenal and gonadal hormones, neurotransmitters, growth factors, certain drugs, environmental stimulation, learning, and aging change neuronal structures and functions. The processes that these factors may induce are morphological alterations in brain areas, changes in neuron morphology, network alterations including changes in neuronal connectivity, the generation of new neurons (neurogenesis), and neurobiochemical changes. Here we review several aspects of neuroplasticity and discuss the functional implications of the neuroplastic capacities of the adult and differentiated brain with reference to the history of their discovery.
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Review Article
Adult Neuroplasticity: More Than 40 Years of Research
Eberhard Fuchs1,2 and Gabriele Flügge1
1German Primate Center, Leibniz Institute for Primate Research, Kellnerweg 4, 37077 G¨
ottingen, Germany
2Department of Neurology, Medical School, University of G¨
ottingen, 37075 G¨
ottingen, Germany
Correspondence should be addressed to Gabriele Fl¨
ugge; g
Received  January ; Accepted  April ; Published  May 
Academic Editor: Paul Lucassen
Copyright ©  E. Fuchs and G. Fl¨
ugge. is is an open access article distributed under the Creative Commons Attribution
License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly
Within the last four decades, our view of the mature vertebrate brain has changed signicantly. Today it is generallyaccepted that the
adult brain is far from being xed. A number of factors such as stress, adrenal and gonadal hormones, neurotransmitters, growth
factors, certain drugs, environmental stimulation, learning, and aging change neuronal structures and functions. e processes
that these factors may induce are morphological alterations in brain areas, changes in neuron morphology, network alterations
including changes in neuronal connectivity, the generation of new neurons (neurogenesis), and neurobiochemical changes. Here
we review several aspects of neuroplasticity and discuss the functional implications of the neuroplastic capacities of the adult and
dierentiated brain with reference to the history of their discovery.
1. Introduction
e term “neuronal plasticity” was already used by the “father
of neuroscience” Santiago Ram´
on y Cajal (-) who
described nonpathological changes in the structure of adult
brains. e term stimulated a controversial discussion as
some neuropathologists favored the “old dogma” that there
be replaced when the cells die (for review see []). In a
wider sense, plasticity of the brain can be regarded as “the
function of the nervous system” []. Accordingly, “neuronal
plasticity” can stand not only for morphological changes in
brain areas, for alterations in neuronal networks including
changes in neuronal connectivity as well as the generation of
new neurons (neurogenesis), but also for neurobiochemical
changes. We provide here a short overview of dierent
forms of neuroplasticity with reference to the history of their
2. Changes in Neuron Morphology
In the late s, the term “neuroplasticity” was introduced
for morphological changes in neurons of adult brains. Using
electron microcopy Raisman [] demonstrated an “anatom-
ical reorganization” of the neuropil in the septal nuclei of
adult rats aer a selective lesion to distinct axons which
changes in the morphology of neurons in response to various
internal and external stimuli have been described. A strong
external stimulus that evokes numerous neuroplastic changes
is stress. Repeated or chronic stress changes the morphol-
ogy of neurons in various brain areas. Probably the most
thoroughly investigated neuromorphological change is the
stress-induced regression of the geometrical length of apical
dendrites of pyramidal neurons that was rst demonstrated in
the hippocampus []. e hippocampus is part of the limbic-
HPA (hypothalamic-pituitary-adrenal) system and regulates
the stress response. Retraction of dendrites of CA pyramidal
neurons has been repeatedly documented aer chronic stress
as well as aer chronic glucocorticoid administration [].
Dendritic retraction does of course reduce the surface of the
neurons which diminishes the number of synapses. Also neu-
rons in the medial prefrontal cortex retract their dendrites in
response to stress, but the eects depend on the hemisphere
[,]. Studies on the prefrontal cortex showed that neurons
in this brain region are particularly plastic in that they change
their dendritic morphology with the diurnal rhythm [].
Hindawi Publishing Corporation
Neural Plasticity
Volume 2014, Article ID 541870, 10 pages
Neural Plasticity
Such neuroplastic reactions are not a one-way road. In the
amygdala, the dendritic arborization of the pyramidal and
stellate neurons in the basolateral complex was enhanced by
a similar chronic stress paradigm that reduces branching of
dendrites in hippocampal CA pyramidal neurons []. e
brain’s pronounced neuroplastic capacities are also reected
by the fact that the synapses are replaced as soon as the
stress is terminated []. Furthermore, drugs that stimulate
neuroplasticity can prevent the stress-induced retraction of
dendrites in the hippocampal formation []. A form of
functional neuroplasticity is long-term potentiation (LTP),
that is the long-lasting enhancement in signal transmission
between two neurons aer synchronous stimulation [].
3. Neuron Death
e research on neuroplasticity in adult brains was strongly
stimulated by observations that brain neurons may die, for
example, because of trauma or degenerative illnesses such
as Parkinsons or Alzheimer’s disease []. In the late s,
there were reports that even the stress that an individual
experiences can kill neurons in the brain. is message
was based on studies in wild vervet monkeys that had
been housed in a primate center in Kenya where they died
suddenly. e animals had experienced severe stress because
of social isolation from their group []. e nding that their
brains revealed dead pyramidal neurons in the hippocampus
attracted great public attention as the message was reduced
to “stress kills neurons.” However, it later turned out that in
thisstudyonwildlifeanimalsthepost mortem treatment
of the brain tissue had been not optimal. e time between
death of the animals and xation of the brains for the
neuropathological analysis was obviously too long so that
morphology of the neurons was aected to an extent that had
nothing to do with the previous stress exposure of the living
animals. Since stress raises plasma glucocorticoids (GC),
monkeys were chronically treated with GC in a subsequent
study, and also the brains of these animals revealed changes
in neuron morphology that were interpreted as dead or
dying neurons []. However, these ndings could not be
conrmed by others. Instead, it was recognized that the
morphological analysis of pyramidal neurons is technically
delicate. It became apparent that, aer a subject’s death,
neurons may dramatically change their morphology and turn
into “dark neurons” when the brain tissue has not been
xed adequately for the histological analysis []. When the
chronic stress experiments were repeated under conditions
that acknowledged those technical issues, it turned out that
stress does not kill neurons, which is denitely a good
message for stressed individuals []. Further studies showed
that apoptosis (programmed cell death) in the hippocampal
formation is a relatively rare event and that chronic stress may
even reduce cell death in certain hippocampal subelds while
increasing apoptosis in others []. Since chronic social stress
in animals is regarded as preclinical model for depression
the nding of a lack of neuron death in stressed animals
also shed new light on a hypothesis saying that, in humans,
major depression kills neurons in the brain. Indeed, it was
later found that hippocampal neuron numbers in depressed
subjects do not signicantly dier from the numbers in
healthy individuals []. Also the hypothesis that chronic
GC exposure leads to neuron death had to be revised. A
summary of a range of studies on these issues concluded
that it is unlikely that endogenous GC can cause structural
damage to the hippocampal formation []. Nevertheless it
is an established fact that “adverse inuences” such as stress,
depression, and chronic GC treatments may cause shrinkage
of the hippocampal formation []. However, the underlying
processes are obviously not neuron loss but other changes
in the tissue such as reductions in neuronal dendrites and
further presumptive alterations in the neuropil that have not
been identied in detail yet ([,]; for review see []).
4. Neurogenesis in Adult Vertebrates
e most appealing phenomenon of neuroplasticity appears
to be adult neurogenesis, that is the generation of new
neurons in adult brains. Neurogenesis takes of course place
in the developing central nervous system, but in view of
the fact that certain illnesses such as Parkinsons disease and
multiple sclerosis occur in adulthood the interesting question
is whether also adult brains are able to replace lost neurons.
In contrast to most cells of the body such as those in the
gut, the skin, or the blood which are constantly renewed, the
brain—and in particular the mammalian brain—has always
been regarded as a nonrenewable organ. Most neurons of the
adult central nervous system appear as terminally dieren-
tiated. Although the adult brain can sometimes functionally
compensate for damage by generating new connections
among surviving neurons, it does not have a large capacity
to repair itself because most brain regions are devoid of stem
cells that are necessary for neuronal regeneration. is lack
of neuroplasticity was rst described by Santiago Ram´
y Cajal who stated that “In adult centers the nerve paths
are something xed, ended, immutable. Everything may die,
nothing may be regenerated. It is for science of the future to
change, if possible, this harsh decree” [].
e “no new neurons” dogma was already challenged
almost ve decades ago. Using autoradiography with the triti-
ated DNA nucleoside 3H-thymidine, Altman [,]gained
rst evidence for the production of glia cells and possibly also
of neurons in the brains of young adult rats and adult cats.
In subsequent studies, -day-old rats received 3H-thymidine
and the tritium radioactivity was visualized  months later
in cells of the subgranular zone in the dentate gyrus [].
Unfortunately, autoradiography with 3H-thymidine is a very
delicate method and it is not easy to pick up the low
number of neurons that is generated daily in, for example, the
dentate gyrus of adult mammals. Accordingly, 3H-thymidine
autoradiographs produced at that time could not generally
convince the scientic community that adult neurogenesis
really exists. us only a limited number of experiments
followed the initial studies mentioned above. However, the
neuronal character of newly generated cells in the rodent
dentate gyrus was conrmed and further substantiated by
demonstrating that these newborn cells receive synaptic input
Neural Plasticity
and extend axons into the mossy ber pathway that projects
to the CA subeld []. Another landmark was in the
early s, when substantial neurogenesis was demonstrated
in a vocal control nucleus of the adult canary brain [],
and a functional link between behavior, song learning, and
the production of new neurons was established []. e
nding that, in songbirds (canaries, zebra nches), males
have larger song control nuclei in their brains as compared
to females indicated that the number of neurons in those
adult birds may change with the season []. Indeed, the
neuron number in song control nuclei increases in spring
time when male zebra nches begin to sing, and newborn
neurons were also found in the HVC (hyperstriatum ventrale,
pars caudalis) of adult canaries []. Studies on the HVC in
birds showed that steroid hormones play important roles in
these processes of neuroplasticity, in particular the gonadal
hormone testosterone [,].
In line with these ndings Cajals statement on the xed
number of neurons in adu lt brains was further challenged as it
became clear that even in mammals, parts of the adult central
nervous system are able to replace neurons. In the olfactory
epithelium of the mammalian nose, sensory neurons are con-
tinuously generated throughout the lifespan, as rst shown in
adult squirrel monkeys []. is electron microscopic study
clearly showed large numbers of newborn sensory neurons
olfactory bulb (OB) of adult mammals can be replaced. e
new OB neurons derive from the subventricular zone at the
lateral ventricle where neuroblasts are generated that migrate
through the rostral migratory stream to the OB (Figure ).
e neuroblasts dierentiate to functional neurons, in that
case granule cells, which formsynapses with mitral cells ([,
]; for review see []). However, OB neurogenesis is easier
to detect than hippocampal neurogenesis and it took several
years until there was reliable evidence that hippocampal
neurogenesis does exist in adult mammals.
In particular, neurogenesis could long not be demon-
strated in the brains of adult nonhuman primates such
as rhesus monkeys thereby leading to the assumption that
neuronal replication is not tolerated in primates. In an initial
study, Rakic [] investigated neurogenesis in adult rhesus
monkeys using 3H-thymidine, examining major structures
the association neocortex, hippocampus andOB. Rakic found
“not a single heavily labeled cell with the morphological
characteristics of a neuron in any brain in any adult animal
and concluded that “all neurons of the rhesus monkey brain
are generated during prenatal and early postnatal life” [,
]. Furthermore, Rakic argued that “a stable population of
neurons may be a biological necessity in an organism whose
survival relies on learned behavior acquired over a long
period of time.” ese statements had a profound inuence
on the development of the research eld in that they formed
the basis for researchers of the time to show little interest to
detect neurogenesis in the adult mammalian brain.
A revolution in the eld of neurogenesis research took
place when the thymidine analog -bromo-󸀠-deoxyuridine
(BrdU) and corresponding antibodies were introduced for
labeling newborn neurons by immunohistochemistry [].
Using this new—and in comparison to autoradiography—
pocampal neurogenesis in mammals is not restricted to
rodents but has been conserved throughout mammalian
evolution. e formation of new granule neurons was, for
example, demonstrated in the dentate gyrus of adult rats and
tree shrews [,]; the later species is regarded as phylo-
genetically located between insectivores and primates [].
Evidence of neurogenesis in the adult primate brain derived
from studies in marmoset monkeys [], a small nonhuman
primate from South America, and in macaques which are
typical representatives of the nonhuman Old-World primates
[,]. Finally, the existence of neurogenesis in the adult
human brain was shown in cancer patients who were injected
with BrdU to monitor tumor cell proliferation. Some of these
patients died from their illness and small samples of their
hippocampi were evaluated for the presence of BrdU-labeled
neurons. Since BrdU had been systemically administered, all
dividing cells were supposed to be labeled. Indeed, newborn
neurons were detected in the dentate gyrus granule cell
layer of all individuals []. ese data unequivocally showed
that adult neurogenesis is a common phenomenon across
mammalian species. It thus became generally accepted that
adult neurogenesis not only does occur in the olfactory
bulb and the gyrus dentatus of the hippocampal formation
of mammals but can also be detected in “higher” brain
regions such as the neocortex [,]. However, there are
still open questions regarding the extent of neurogenesis in
homologous brain regions of dierent mammalian species
(see below).
To detect neurogenesis in brains of adult humans the
group of J. Fris´
en took advantage of the increased concentra-
tion of 14C in the atmosphere aer nuclear bomb tests [].
Aer a nuclear explosion, this radioisotope is increasingly
incorporated into dividing cells of living organisms, including
humans. rough the determination of 14C, the authors
found that about  new neurons are generated daily in
the hippocampal formation of adult humans. Interestingly,
the 14C analysis of human brains revealed adult neurogenesis
in the striatum, adjacent to a site at the lateral ventricle
where neuronal precursor cells are generated, and there
are indications that the neuroblasts in the human striatum
dierentiate to interneurons []. Surprisingly, no newborn
neurons could be detected with the 14C technique in the
species and brain-region specic processes of neurogenesis
await further elucidation.
Adult neurogenesis does occur not only in mammals
and birds but also in amphibians, reptiles, and bony shes
(for references see []). Despite this omnipresence of adult
neurogenesis within vertebrates, comparative studies have
revealed signicant dierences between classes. So far it
neurons in adult brains takes place in two regions, the
subventricular zone and the dentate gyrus, and the number
Neural Plasticity
(2) Neurogenesis
in the dentate
gyrus (DG)
(1) Generation of stem
zone (SVZ)
cells in the
by olfactory
Positive modulators:
Environmental stimuli
Exercise (running)
Negative modulators:
Acute and chronic stress
NMDA receptor activation
F : A schematic view on adult neurogenesis. Neuronal progenitor cells are generated in the subventricular zone (SVZ) and in the dentate
gyrus (DG) of the hippocampal formation (Hip). () In the SVZ, neuroepithelial progenitor cells are generated that migrate through the RMS
(rostral migratory stream) to the olfactory bulb (OB). ey dierentiate to mature neurons and are integrated as functional elements into the
neuronal olfactory circuitry. () In the DG, quiescent neural progenitors (a) become amplifying neural progenitors (b) that dierentiate rst
to neuroblasts (c), then to immature neurons (d), and nally to functionally mature granule neurons (e).
of newly generated neurons is small compared to the total
number of brain cells (Figure ). However, there are also
reports from studies in mice that new neurons can be
generated in the adult substantia nigra, although with “a slow
physiological turnover of neurons” []. In contrast, in sh
a huge number of neurons are continuously produced in
many areas of the adult brain []. Also important to mention
that in comparison with shes, reptiles and birds, the rate of
neurogenesis in adult mammals decreases with age [].
5. Regulators of Adult Neurogenesis
e existence of neurogenesis in adult brains gives hope that
even damaged brain regions can be functionally repaired.
Indeed, injury to the adult brain such as ischemic insults stim-
ulates the proliferation of subventricular zone cells and thus
the formation of neuronal precursor cells. ese neuroblasts
migrate along blood vessels to the damaged region (for review
see []). However, only a small percentage can survive,
in part because inammatory processes that occur in the
ischemic brain region inhibit neurogenesis and the successful
integration of new cells into a functional neuronal network
[]. Anti-inammatory drugs can restore neurogenesis, as
shown in rodent models of peripheral inammation and aer
irradiation [].
Knowledge about the regulation of adult neurogenesis is
denitely a prerequisite for future therapeutic interventions
that may take advantage of the generation of new neurons in
adult brains. Kempermann [] emphasized that there is an
“immense spectrum of neurogenic regulators” which reect
“the sensitivity of adult neurogenesis to many dierent types
of stimuli.” Respective regulatory elements that are so far
known include single molecules as well as environmental
conditions that lead to changes in a large number of fac-
tors which themselves inuence neurogenesis. Among the
molecular factors that were rst identied as regulators of
adult neurogenesis are sex steroids such as estrogen which
can at least transiently stimulate neurogenesis in the dentate
gyrus []. Steroid hormones have pleiotropic eects on the
expression of many genes among which are also genes which
themselves encode regulators of neurogenesis. Accordingly,
in female mammals, eects of steroid hormones on adult
neurogenesis depend on the estrous cycle and other stages
related to reproductive biology []. It is not surprising that
growth factors such as BDNF (brain-derived neurotrophic
factor) and VEGF (peripheral vascular endothelial growth
factor) regulate adult neurogenesis []. Also the neuro-
transmitter glutamate and astroglia have an impact on adult
neurogenesis, probably by generating a distinct microen-
vironment that may favor the generation/dierentiation of
neuroblasts []. e large number of factors that regulate
adult neurogenesis has been reviewed before [].
Eects of stress on neurogenesis in the dentate gyrus
(the so-called hippocampal neurogenesis) have been studied
by several groups. Chronic social stress in tree shrews
and other adverse stress experiences in marmoset monkeys
reduced hippocampal neurogenesis [,,]. e eects
of social and other forms of stress depend on the stressor’s
intensity and its duration, and they may be reversible [].
Prenatal stress in rhesus monkeys has persistent eects as
a reduction in neurogenesis was observed in the adolescent
individuals []. In newborn marmoset monkeys which
were intrauterinely exposed to the synthetic glucocorticoid
dexamethasone, the proliferation of putative precursor cells
but not the dierentiation into mature cells was impaired
[]. Interestingly, this decreased proliferation rate observed
in newborn monkeys was no longer detectable in their -
year-old siblings suggesting no long-lasting eect of prenatal
hyperexposure to dexamethasone on neuronal proliferation
and dierentiation in the dentate gyrus of marmoset mon-
keys [].
Several authors attributed the eects of stress on neuro-
genesis to the actions of glucocorticoids which are elevated in
Neural Plasticity
(a) (b)
(c) (d)
F : Electron micrographs of pyramidal neuron nuclei in the hippocampus of control and stressed male tree shrews: (a), control
CA; (b), stress CA; (c), control CA; (d), stress CA. Note the homogeneous nucleoplasma (NP) in the controls and the large number
of heterochromatin clusters (arrow) in nuclei of CA pyramidal neurons in stressed animals. NL: nucleolus. Calibration bar:  𝜇m.
the blood of stressed individuals. Corticosteroids do indeed
regulate neurogenesis and the glucocorticoid receptor antag-
onist mifepristone prevented the stress-induced reduction in
hippocampal neurogenesis []. Also the mineralocorticoid
receptor appears to play a particular role as indicated by the
fact that a genetic disruption of the receptor impaired adult
hippocampal neurogenesis in mice []. However, elements
of the glucocorticoid system are not the only regulatory
factors of adult neurogenesis in stress. Instead, as pointed
out above, other components of the stress cascade such as
enhanced excitatory neurotransmission (increased glutamate
release) play also a role. In several preclinical models of
depression using stress to induce depressive-like symptoms
in animals, certain antidepressants restored the neurogenesis
that had been impaired by the stress (see, e.g., [,]). ere
are indications that antidepressants activate the glucocorti-
coid receptor which may increase hippocampal neurogenesis
[]. However, it remains an enigma whether endogenous or
synthetic substances exist that can boost adult neurogenesis
via this receptor system.
e formation of new neurons is regulated by substances
derived from blood vessels and is targeted by an enormous
number of factors [,]. Coinciding with this view are
reports demonstrating that adult neurogenesis is enhanced by
physical activity such as running [], by learning [], or by
environmental enrichment [].
6. Functional Role of Adult Neurogenesis
Soon aer the discovery of adult neurogenesis it was hypoth-
esized that hippocampal neurogenesis (i.e., the neurogenesis
in the subgranular zone of the dentate gyrus, a region of
the hippocampal formation) plays a crucial role in learning
and memory []. However, experimental results on the
role of dierent forms of memory in adult rodents (e.g.,
spatial learning versus associative memory) were in part
Neural Plasticity
Control Stress Cortisol
Relative number/nucleus
Relative number/nucleus
Control Stress Cortisol
F : Relative number of heterochromatin clusters in electron micrographs from nuclei of pyramidal cells in CA and CA. Data are
mean ±SEM (𝑃 ≤ 0.0001).
contradictory. In a comprehensive review, Koehl and Abrous
[] came to the conclusion that adult neurogenesis in
rodents is involved “when the task requires the establishment
of relationships among multiple environmental cues...for the
exible use of acquired information.” Whether this is true
for all mammals remains to be determined as a low rate or
even absence of neurogenesis was found in the hippocampal
formation of adult bats []andinwhales[], species with
an excellent spatial working memory. In the OB, adult-born
new neurons are integrated into the neuronal circuits that are
responsible for olfaction and olfactory memory, respectively
(for review see []).
e fact that in animal models of depression certain
antidepressants restored normal neurogenesis that had been
impaired by stress led to the hypothesis that the bene-
cial eects of antidepressants depend on the restoration of
normal neurogenesis []. e volume of the hippocampal
formation is reduced in patients with major depression, and
antidepressants can normalize hippocampal volume [].
decrease in neurogenesis but rather to morecomplex changes
in the neural network which involve dendritic, axonal, and
possibly also glial alterations []. Kempermann et al. []
proposed that “failing adult hippocampal neurogenesis may
not explain major depression, addiction or schizophrenia,
but contributes to the hippocampal aspects of the diseases.
A comparison of the neural stem-cell proliferation in post
mortem brain samples from patients with major depres-
sion, bipolar aective disorder, schizophrenia, and control
subjects revealed no evidence of reduced neurogenesis in
the dentate gyrus of depressed individuals. Furthermore,
antidepressant treatment did not increase neural stem-cell
proliferation. Unexpectedly, signicantly reduced numbers
of newly formed cells were found only in schizophrenic
patients []. Concerning impaired neurogenesis as presump-
tive cause of depression a group of experts summarized that
“a lasting reduction in neurogenesis” ... (is) “unlikely to
produce the full mood disorder” []. However, more recent
reports based on post mortem studies showed decreased
numbers of neuronal progenitor cells in the dentate gyrus
of depressed patients and a selective enhancing eect of
antidepressant treatment in the anterior and middle den-
tate gyrus of depressed individuals []. To overcome
the manifold limitations of post mortem studies, a future
approach to address the question of adult neurogenesis in
humans more precisely (possibly in longitudinal studies)
could be the visualization of this process in live subjects
using advanced in vivo imaging techniques. Moreover, this
approach could help answer the open questions on the role of
neurogenesis in cognitive functions and its functional impact
and contribution to the etiology of depression.
7. Chromatin Changes
When searching for dead neurons in the hippocampal for-
mation of male tree shrews, standard histology showed that
changes the appearance of the nuclei in the hippocampal neu-
rons []. Closer investigations revealed that chronic stress
increases the formation of heterochromatin in the nuclei of
the hippocampal neurons []. In this study, the nuclear
ultrastructure of hippocampal pyramidal neurons in male
tree shrews that had been exposed to daily social stress during
four weeks according to a standard stress paradigm was
analyzed. Electron microscopic analysis revealed that in the
stressed animals the nucleoplasma of CA pyramidal neurons
displayed numerous heterochromatin clusters (Figure ).
Heterochromatin is a form of condensed chromatin whose
occurrence indicates that transcription of genes is reduced
in those cells. Quantication of the clusters revealing areas
larger than 𝜇m2in the hippocampal region CA showed
Neural Plasticity
that there was more heterochromatin in stressed animals
compared to controls. In contrast, in area CA, the stress had
no eect on the density of heterochromatin clusters (Figure ;
[]). Although in those days it was totally unknown which
genes in the hippocampal nuclei were “silenced” by the
chronic stress, these morphological data indicated already
what was later called “epigenetics,” the phenomenon that
environmental factors change the structure of chromatin,
inuence transcription, and induce changes in the genome
[]. Since glucocorticoid hormones are oen regarded as
important factors that convey many eects of chronic stress,
it was tested whether a chronic cortisol treatment would
stress. Interestingly, chronic cortisol changed the number of
heterochromatin clusters only in hippocampal region CA,
but not in CA, the region that is targeted by stress (Figure ).
ese results indicate a site and treatment specic reaction
to stress and glucocorticoid treatment in the hippocampal
formation. e obvious dierences between chronic stress
and chronic glucocorticoid treatment must be kept in mind
because they possibly reect dierent cellular pathways acti-
vated by the two treatments.
Conflict of Interests
e authors declare that there is no conict of interests
regarding the publication of this paper.
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... In the 1960s, it was discovered that neurons could "reorganize" after a traumatic event. Further research found that stress can change not only the functions but also the structure of the brain itself [3]. ...
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In this work, an innovative framework for an electro-tactile display system for blind and impaired persons has been proposed. The creation of visual data over another sense is modelled in this proposed system using the neuroplasticity approach. The suggested framework's aim is to simulate a tactile stimulus in the hands and to create the vision on the skin of the hands. It is aimed to process the depth map of the surroundings in real-time as visual perception, and a Microsoft Kinect camera with infrared sensors is utilized for this purpose. For hardware and software applications to be created in future studies, a theoretical connection has been designed between electro-tactile display and depth map. The proposed electro-tactile system and depth map has been simulated briefly.
... Plasticity is the broader dynamic change in the structure and function of nervous tissue (Fuchs and Flügge, 2014). In some animals, learned behaviors can be disrupted temporarily if the relevant tissue is damaged but will be recovered if allowed the time for other neural structures to modify their activity and compensate for the loss (Otchy et al., 2015). ...
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The brain-as-computer metaphor has anchored the professed computational nature of mind, wresting it down from the intangible logic of Platonic philosophy to a material basis for empirical science. However, as with many long-lasting metaphors in science, the computer metaphor has been explored and stretched long enough to reveal its boundaries. These boundaries highlight widening gaps in our understanding of the brain’s role in an organism’s goal-directed, intelligent behaviors and thoughts. In search of a more appropriate metaphor that reflects the potentially noncomputable functions of mind and brain, eight author groups answer the following questions: (1) What do we understand by the computer metaphor of the brain and cognition? (2) What are some of the limitations of this computer metaphor? (3) What metaphor should replace the computational metaphor? (4) What findings support alternative metaphors? Despite agreeing about feeling the strain of the strictures of computer metaphors, the authors suggest an exciting diversity of possible metaphoric options for future research into the mind and brain.
... Néanmoins, le phénomène de plasticité le plus attrayant chez l'adulte semblerait être la neurogenèse, soit la génération de nouveaux neurones chez l'adulte. Ce phénomène a lieu lors du développement du système nerveux central, mais jusqu'à récemment, le système nerveux central était considéré comme un organe non régénérable, contrairement à la peau ou au sang où les cellules sont constamment renouvelées (Fuchs and Flügge, 2014). Bien qu'il puisse parfois fonctionnellement compenser la perte de neurones suite à un trauma en générant de nouvelles connexions synaptiques (Cajal, 1930). ...
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... In some stroke patients suffering damage to motor networks on one hemisphere, motor networks on the unaffected hemisphere demonstrate changes in activity that appear to compensate for the functional losses during recovery (Bajaj et al., 2016;Liu et al., 2015). Plasticity is the broader dynamic change in the structure and function of nervous tissue (Fuchs and Flügge, 2014). In some animals, learned behaviors can be disrupted temporarily if the relevant tissue is damaged but will be recovered if allowed the time for other neural structures to modify their activity and compensate for the loss (Otchy et al., 2015). ...
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The computer metaphor derives from two parallel histories of thought, the first questioning the operation and activity of minds and brains and the second aiming at finding a minimal model of the mind and brain. These histories informed separate hypotheses of mind, epistemic constructivism, and the mechanistic hypothesis; we focus on the latter. First, we briefly review how the brain has historically been discussed with machine metaphors and identify five tenets that define a machine. We review findings in neuroscience that motivate that the brain demonstrates exceptions to these tenets and thus ought not to be considered a machine. We offer that an alternative classification may be found in far-from-equilibrium self-organizing systems known as dissipative structures. We review the properties of these systems and suggest that the brain is more like a dissipative structure than a machine. If brains do not fit the mechanistic hypothesis underwriting the computer metaphor, then the cognitive sciences may need to seek alternative metaphors based on the assumption that minds and brains are other natural systems, namely dissipative structures.
Brain neuroplasticity is central for learning and memory. It allows us to respond to the changes in the environment. Neuroplasticity, a life-long process that mediates the structural and functional reaction of neuronal structures to experience, attrition, and injury, plays an imperative role in recovery. Understanding the ability of the nervous system to adapt or modify functions and compensate for damage is critical to improving rehabilitative strategies and optimizing functional outcomes. For a long time, the hardware of the brain was considered “hard” and believed to be never restorable following neurological conditions like stroke or traumatic brain injury. However, the current data suggest that neurons possess a remarkable ability to alter their structure and function to a variety of internal and external pressures, including rehabilitative training. Evidence also strongly suggests that rehabilitative training is the most successful means to enhance functional recovery following such incidences. This chapter provides an overview of the historical background, different forms of neuroplasticity, and plasticity within the developing and adult brains.
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Social isolation is defined, in psychological terms, as the absence of meaningful social interactions, contacts, and relationships with family and friends, with neighbors. It can occur on an individual level and, on a broader level, within “society at large.” In the United States, three main groups of socially isolated individuals can be identified: people who reside in assisted-living facilities, nursing homes, or hospices, people suffering from “persistent loneliness” and people incarcerated in jails or prisons who are housed in involuntary solitary confinement. In this chapter, we discuss the psychological and neurobiological effects of isolation, using both animal models as well as direct studies of humans experiencing these conditions. Only by understanding the impact of isolation on the brain and the mechanisms that underlie these changes can we hope to develop interventions that prevent them from occurring in the first place. This knowledge may also contribute to the efforts of psychologists, clinicians, and community health leaders to employ evidence-based prevention programs to mitigate the risk of isolation-induced physical and psychological damage in humans.
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Neural stem cells in the mammalian adult brain continuously produce new neurons throughout life. Accumulating evidence in rodents suggests that various aspects of adult neurogenesis, including the genesis, migration, and maturation of new neurons, are regulated by factors derived from blood vessels and their microenvironment. Brain injury enhances both neurogenesis and angiogenesis, thereby promoting the cooperative regeneration of neurons and blood vessels. In this paper, we briefly review the mechanisms for the vascular regulation of adult neurogenesis in the ventricular-subventricular zone under physiological and pathological conditions, and discuss their clinical potential for brain regeneration strategies.
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Environmental challenges are part of daily life for any individual. In fact, stress appears to be increasingly present in our modern, and demanding, industrialized society. Virtually every aspect of our body and brain can be influenced by stress and although its effects are partly mediated by powerful corticosteroid hormones that target the nervous system, relatively little is known about when, and how, the effects of stress shift from being beneficial and protective to becoming deleterious. Decades of stress research have provided valuable insights into whether stress can directly induce dysfunction and/or pathological alterations, which elements of stress exposure are responsible, and which structural substrates are involved. Using a broad definition of pathology, we here review the "neuropathology of stress" and focus on structural consequences of stress exposure for different regions of the rodent, primate and human brain. We discuss cytoarchitectural, neuropathological and structural plasticity measures as well as more recent neuroimaging techniques that allow direct monitoring of the spatiotemporal effects of stress and the role of different CNS structures in the regulation of the hypothalamic-pituitary-adrenal axis in human brain. We focus on the hypothalamus, hippocampus, amygdala, nucleus accumbens, prefrontal and orbitofrontal cortex, key brain regions that not only modulate emotions and cognition but also the response to stress itself, and discuss disorders like depression, post-traumatic stress disorder, Cushing syndrome and dementia.
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The hippocampus is essential for the formation and retrieval of memories and is a crucial neural structure sub-serving complex cognition. Adult hippocampal neurogenesis, the birth, migration and integration of new neurons, is thought to contribute to hippocampal circuit plasticity to augment function. We evaluated hippocampal volume in relation to brain volume in 375 mammal species and examined 71 mammal species for the presence of adult hippocampal neurogenesis using immunohistochemistry for doublecortin, an endogenous marker of immature neurons that can be used as a proxy marker for the presence of adult neurogenesis. We identified that the hippocampus in cetaceans (whales, dolphins and porpoises) is both absolutely and relatively small for their overall brain size, and found that the mammalian hippocampus scaled as an exponential function in relation to brain volume. In contrast, the amygdala was found to scale as a linear function of brain volume, but again, the relative size of the amygdala in cetaceans was small. The cetacean hippocampus lacks staining for doublecortin in the dentate gyrus and thus shows no clear signs of adult hippocampal neurogenesis. This lack of evidence of adult hippocampal neurogenesis, along with the small hippocampus, questions current assumptions regarding cognitive abilities associated with hippocampal function in the cetaceans. These anatomical features of the cetacean hippocampus may be related to the lack of postnatal sleep, causing a postnatal cessation of hippocampal neurogenesis.
Most neurons in the mammalian brain are produced during the embryonic period. In contrast, the granule cell population of the dentate gyrus of the hippocampal formation is produced during an extended period that begins during gestation and continues well into adulthood. The production of new granule neurons is suppressed by stress. These observations suggest that stressful experiences during postnatal development and adulthood have the potential to alter significantly both the structure and function of the hippocampal formation. Because the hippocampus plays a key role in learning and memory, a decrease in the production of granule neurons during development may have a negative impact on learning and memory in adulthood.
In most mammals, neurons are added throughout life in the hippocampus and olfactory bulb. One area where neuroblasts that give rise to adult-born neurons are generated is the lateral ventricle wall of the brain. We show, using histological and carbon-14 dating approaches, that in adult humans new neurons integrate in the striatum, which is adjacent to this neurogenic niche. The neuronal turnover in the striatum appears restricted to interneurons, and postnatally generated striatal neurons are preferentially depleted in patients with Huntington's disease. Our findings demonstrate a unique pattern of neurogenesis in the adult human brain.
We present evidence for continuous generation of neurons, oligodendrocytes, and astrocytes in the hippocampal dentate gyrus of adult macaque monkeys, using immunohistochemical double labeling for bromodeoxyuridine and cell-type-specific markers. We estimate that the relative rate of neurogenesis is approximately 10 times less than that reported in the adult rodent dentate gyrus. Nevertheless, the generation of these three cell types in a discreet brain region suggests that a multipotent neural stem cell may be retained in the adult primate hippocampus. This demonstration of adult neurogenesis in nonhuman Old World primates-with their phylogenetic proximity to humans, long life spans, and elaborate cognitive abilities-establishes the macaque as an unexcelled animal model to experimentally investigate issues of neurogenesis in humans and offers new insights into its significance in the adult brain.