Review Article
The Role of Neural Plasticity in Depression:
From Hippocampus to Prefrontal Cortex
Wei Liu,
1,2
Tongtong Ge,
1
Yashu Leng,
3
Zhenxiang Pan,
2
Jie Fan,
1
Wei Yang,
1
and Ranji Cui
1
1
Jil i n Provincial Key Laboratory on Molecular and Chemical Genetic, e Second Hospital of J ili n U niversity ,
218 Ziqiang Street, Changchun 130041, China
2
Anesthesiology Department, e Second Hospital of Jilin University , 218 Ziqiang Street, Changchun 130041, China
3
Anesthesiology Department, e ird Hospital of Jilin University, 126 Xiantai Street, Changchun 130033, China
Correspondence should be addressed to Wei Yang; wyang@jlu.edu.cn and Ranji Cui; cuiranji@jlu.edu.cn
Received November ; Accepted January ; Published January
Academic Editor: Aijun Li
Copyright © Wei Liu et al. is is an open access article distributed under the Creative Commons Attribution License, which
permits unrestricted use, distributio n, and reproduction in any medium, provided the original work is properly cited.
Neural plasticity, a fundamental mechanism of neuronal adaptat ion, is disrupted in depression. e changes in neural plasticity
induced by stress and other negative stimuli play a signicant role in the onset and development of depression. Antidepressant
treatments have also been found to exert their antidepressant eects through regulatory eects on neural plasticity. However, the
detailed mechanisms of neural plasticity in depression still remain unclear. erefore, in this review, we summarize the recent
literature to elaborate the possible mechanistic role of neural plasticity in depression. Taken together, these ndings may pave the
way for future progress in neural plasticity studies.
1. Introduction
e establishment and realization of neural functions are
based on generation, transformation, and storage of infor-
mation in neural networks. e brain is developing and
progressing at high speed in the six- to nineteen-year-old
agegroup,andtheuniqueplasticityofneuraldevelopment
is crucial to mature neural function. In a neural network,
neurons are the fundamental functional units that integrate
and transmit signals in response to intrinsic and extrinsic
information []. Neuronal functions are dynamic processes
that occur in response to environmental stimuli, emotions,
injury,andsoforth.isisthetheoreticalbasisofneuralplas-
ticity, which is an umbrella term to describe structural and
functionalchangesinthebraininresponsetovariousstimuli,
including stress and depression. Depression is a prevalent,
chronic, and recurrent disease. Depression, one of most
devastating diseases, has a worldwide lifetime prevalence of
%. Moreover, to patients with depression, depression not
only brings profound mental agony but also causes patho-
physiological disorders and enhances susceptibility to some
diseases, for instance, cardiac diseases and cerebrovascular
illness []. erefore, patients with depression suer from
higher mortality than the healthy population. Unfortunately,
to date, no completely eective treatments for depressed
patients have been developed. Currently available antide-
pressant treat ments, whether medications, psychotherapies,
or other methods, have limited ecacy in depression and
can cause signicant side eects []. Hence, it is profoundly
signicant to explore the pathophysiology of depression.
ough a large number of studies on the correlation between
depression and neural plasticity have revealed some of their
mechanisms, the neurobiological mechanisms of depression
are still not well known. Negative stimuli, such as stress,
pain, and cognitive impairment, can result in both depression
andchangesinneuralplasticity.eneuroplasticityhypoth-
esis of major depressive disorder proposes the theory that
dysfunction of neural plasticity is a basic pathomechanism
of the disorder []. However, depression is not an inex-
orable outcome of dysfunction of neural plasticity. To our
knowledge, there are no authoritative research results or
expert consensus to conrm whether depression or changes
Hindawi
Neural Plasticity
Volume 2017, Article ID 6871089, 11 pages
https://doi.org/10.1155/2017/6871089
Neural Plasticity
in neural plasticity are the initial factor. Most of the studies
suggest that depression and dysfunction of neural plasticity
act on and inuence each other. In this perspective, we review
the recent literature to elaborate what is known about neural
plasticity in depression to pave the way for ongoing and future
studies.
2. Hippocampal Plasticity in Depression
e hippocampus is the most commonly studied brain region
in depression research. From a structural point of view, the
hippocampus is part of the limbic system and develops nerve
ber connectivity with emotion-related brain regions, for
instance, the prefrontal cortex and amygdala. In addition, the
hippocampus contains high levels of glucocorticoid receptors
and glutamate and regulates the hypothalamus-pituitary-
adrenal (HPA) axis, which makes it more susceptible to
stress and depression. Changes in hippocampal plasticity can
result from stress and other negative stimuli. Stress impacts
hippocampal plasticity in many ways. Chronic and severe
stress has been shown to impair hippocampus-dependent
explicit memory in animal models of depression []. is
eect can be explained by changes in hippocampal synaptic
plasticity modeled by long-term potentiat i on (LTP) and long-
term depression (LTD). Hippocamp al synaptic plasticity is
widely considered to play an important role in hippocampus-
dependent explicit memory formation []. S evere stress can
impair LTP and enhance LTD in the hippocampi of rodent
models [, ]. Stress can also decrease neuronal dendrite
branching and plasticity in the hippocampus []. In addition,
stress can trigger activation of the hypothalamic-pituitary-
adrenal axis, increase level of corticosteroids, and downreg-
ulate hippocampal neurogenesis []. Cognitive impairment
can enhance long-term potentiation in the CA region and
markedly elevate protein levels of the 𝛼-amino--hydroxy-
-methyl--isoxazolepropionic acid (AMPA) receptor sub-
unit GluA in the mouse hippocampus and then induce
depression in mouse models []. In addition, neuropathic
pain-induced depressive-like behavior may be associated
with hippocampal neurogenesis and plasticity through tumor
necrosis factor receptor signaling []. Hippocampal plastic-
ity in depression involves hippocampal volumetric changes,
hippocampal neurogenesis, and a poptosis of hippocampal
neurons.
2.1. Synaptic Plasticity in the Hippocampus. Synaptic plastic-
ity is one of the most fundamental and important functions of
the brain. e ecacy of transmission at a synapse depends
on modulation of the connectivity between neurons and
neuronal circuits during adaptation to the environment [].
Stress has profound eects on synaptic plasticity in the
hippocampus and presents dierent inuences in dierent
subelds of the h ippocampus. Stress can impair LTP in
CA while facilitating LTD and spike-timing-dependent LTD
(tLTD) in CA []. In addition, depression can downregulate
synaptic proteins and growth factors required for hippocam-
pal LTP in animal models.
Electroacupuncture can alleviate depression-like behav-
iors and reverse the impairment induced by long-term
potentiation in the CA synapses of the hippocampus in
depressive r ats []. Physical exercise may prevent changes
in synaptic plasticity and increases in synaptic transmission
in hippocampal CA pyramidal neurons caused by stress
but cannot reverse the present glutamatergic synaptic alter-
ations induced by depression []. Glucocorticoid receptor
antagonists and monoaminergic antidepressants can pro-
tect against negative synaptic plasticity in CA induced by
stress. TJZL, a monoacylglycerol lipase inhibitor, exhib-
ited antidepressant eects by enhancing adult neurogenesis
and long-term synaptic plasticity in the dentate gyrus of the
hippocampus []. L ycium barbarum was found to reduce
depression-like behavior mediated by enhanced synaptic
plasticity in the hippocampus of rats [].
2.2. Hippocampal Volumetric Changes in Depression. It has
been widely reported that there is a sig nicant reduction
in hippocampal volume in depression patients []. is
situation was found in both adult and adolescent depressed
patients, whether they were in their rst or recurrent depres-
sive episodes. A recent study reported that, in female patients
with recurrent familial pure depressive disorder (rFPDD),
volumetric reductions of the right hippocampal body and tail
were signicantly larger than those of the le, while the whole
brain volume was approximately equal to that of healthy
subjects []. Consistent with this, a signicant increase in
right hemispheric hippocampal gray matter volume has been
found in elderly patients with severe depression treated with
electroconvulsive therapy [, ]. However, hippocampal
volumetric reduction was also found in patients who had
recovered from depression []. e volumetric changes may
result from a neurodegenerative reaction to increased gluco-
corticoid levels in depression []. e changes in synaptic
plasticity induced by depression are associated with struc-
tural and functional changes in the hippocampus. e volume
reduction of the prefrontal cortex and hippocampus may
also result from the disruption and atrophy of neurons and
glia in depression [, ]. Nonetheless, the hippocampal
volumetric changes are not associated with the severity of
depression []. Evidence supports that larger hippocampal
volumes indicate quicker recovery in depressed individuals
[]. is can be explained by hippocampal regulation in
stress reactivity. Reduced hippocampal volumes may be a
neural scar marker of depression and a vulnerability marker
for future episodes []. e clinical application of hippocam-
pal volumetric changes still needs large-sample research to
conrm.
2.3. Hippocampal Neurogenesis. Brain neurogenesis lasts
from birth to adulthood in many animals, including humans.
Hippocampal neurogenesis occurs markedly in the dentate
gyrus, with approximately granule cells born daily, cor-
responding to an annual turnover of .% of the neurons
within the renewing fraction [].
e rate of hippocampal neurogenesis decreases mod-
estly with age. Compared with the millions of granule cells in
the granular layer of the hippocampus, newborn neurons are
few in number, but they can be sucient to achieve functional
Neural Plasticity
signicance []. ough the rates of neuronal regenera-
tion are comparable in middle-aged humans and mice, the
patterns of adult hippocampal neurogenesis are signicantly
dierent between them. In humans, approximately one-third
of hippocampal neurons are subject to exchange. By contrast,
the proportion is % in mice []. e relative decline rate
of hippocampal neurogenesis during adulthood in humans is
lower than that in mice. In addition, hippocampal neurogene-
sis in mice is additive, and newborn neurons can compensate
for lost cells, while new neurons in humans cannot keep up
with the losses []. erefore, hippocampal neurogenesis in
humansmayhaveanadditivefunctioninthecircuitryand
enhance synaptic plasticity to achieve maximum impact.
e neurogenic hypothesis of depression emphasizes the
theory that impaired adult hippocampal neurogenesis results
in depression, and newborn neurons in the adult brain
are critical to mood regulation and antidepressant ecacy
[, ]. Impaired adult hippocampal neurogenesis and
depression may be reciprocally causative []. High levels of
glucocorticoids in depression also hinder adult hippocampal
neurogenesis, but adrenalectomy can promote adult hip-
pocampal neurogenesis.
e eects of antidepressant treatments on adult hip-
pocampal neurogenesis have shown discrepancies in dierent
species. In rodents, most antidepressant treatments that are
used in humans, including electroconvulsive shock and med-
ication, were subsequently shown to facilitate hippocampa l
neurogenesis [–]. However, the facilitation of uoxetine
treatment was sensitive to stress, corticosterone levels, and
route of medication []. e eects of uoxetine treatment
on non-human primates are similar to those in rodents. In
addition, elect roconvulsive shock can also b oost hippocam-
pal neurogenesis in non-human primates []. ere is a
lack of research data to illustrate the eects of medicat ion on
non-h uman primates. In human s, total dentate granule cell
number and dentate gyrus size in me dicated patients with
depression are larger t han those in nonmedicated patients
based on p ost mortem studies []. Selective serotonin reup-
take inhibitors, lithium treatment, and electroconvulsive
shock produce larger increases in hippocampus volume in
treated depressed patients than in nontreated patients [,
]. In line with this observation, research evidence from
thehippocampalsubeldshasrevealedlargerdentategyriin
medicated depressed patients []. ese data are relevant to
multiple forms of neural plasticity and suggest an increase
in hippocampal neurogenesis. Nevertheless, there is no ade-
quate evidence to establish that hippocampal neurogenesis
is necessary for antidepressant ecacy, and its increase is
sucient for ant idepressive therapy.
2.4. Hip pocampal Apoptosis in Depression. Proliferation, dif-
ferentiation, and apoptosis are continuous progressions in
adult hippocamp al neurons. Many studies have demonst rated
that depression and stress can induce hippocam pal apoptosis
in rodents, non-human mammals, and humans, though
hippocampal apoptosis can also be found in nondepressed
rodents []. Similarly, hippocampal apoptosis may result in
depression. Evidence showed an increase of apoptosis in den-
tate gyrus of maternal rats with repeated separation of their
pups and impairment of memory capability with depression-
like behavioral changes []. In maternal-separation rat
models, tadalal, a phosphodiesterase type inhibitor, exerts
antidepressant eects b y suppressing maternal-separation-
induced apoptosis and increasing cell proliferation in the
dentate gyrus []. ough some studies support the idea that
hippocampal apoptosis is a causative factor in hippocampal
volumetric changes, histopathological studies on depressed
patients have yielded inconsistent results []. ere are dif-
ferences in the stimulative eects of chronic depression and
acute depression on hippocampal apoptosis. In animal mod-
els and human studies, chronic depression showed longer
lasting apoptosis-promoting eects in the hippocampus
than acute depression []. e apoptosis-promoting eects
induced by acute depression can fully subside in one day of
recovery, while the adverse eects in chronic depression may
need up to three weeks for recovery. However, it is uncertain
in what stage depression and stress start to mediate apoptosis
progression. In addition, their eects showed dierences
among subelds of the hippocampus. Compared with the
apoptosis increase in the whole dentate gyrus caused by acute
depression, the number of cells in the granular cell layer can
increase even as the cell count in the whole dentate gyrus is
declining [ ]. is discrepancy may be due to the dierent
sensitivities of granular cells to acute and chronic stress.
In addition to tadalal (mentioned above), several types
of drugs may have antidepressant eects owing to hippocam-
pal apoptosis. For instance, venlafaxine, a serotonin/nore-
pinephrine dual reuptake inhibitor, suppresses hippocampal
apoptosis by upregulat ing brain-derived neurotrophic factor
[]. In addition, uoxetine, a -hydroxytryptamine reuptake
inhibitor, regulates hippocampal plasticity by alleviating the
upregulation of synaptosomal polysialic neural cell adhesion
molecule caused by depression and elicits an antiapoptotic
response in the hippocampus [].
3. The Prefrontal Cortex in Depression
e prefrontal cortex (PFC), as a signicant nerve center of
thinking and behavior regulation in the brain, is also associ-
ated with depression []. In view of anatomical connectivity
and f unctional specialization, the prefronta l cortex is divided
into two subregions: ventromedial prefrontal cortex (vmPFC)
and dorsolateral sectors (dlPFC) []. VmPFC involves the
regulation of aection, including the generation of negative
emotion, and dlPFC mediates cognitive functions, such as
intention formation, goal-directed action, and attentional
control []. e two sectors have both been shown to have
signicant roles in depression. However, their eects present
discrepancies, according to reports in the literature. Func-
tional imaging studies have shown opposite changes of activ-
ity in the two sectors: during the progression of depression,
hyperactivity appeared in the vmPFC, while hypoactivity
appeared in dlPFC; in the recovery phase in response to
psychotherapy or medication for depression, hypoactivity
was found in the vmPFC, while hyperactivity was found in
dlPFC [, –]. Furthermore, in lesion models, dlPFC loss
can aggravate depression, whereas vmPFC loss can exhibit an
alleviativeeectondepression[,].Dysfunctioncaused
Neural Plasticity
by dlPFC damage in stroke is considered a predisposing
factor to poststroke depression []. In addition, a decrease
of cortical thickness in the right vmPFC, which occurs in
the early stages of neurodevelopment, results in depression in
preschoolers []. Volume reduction of the prefrontal cortex
may result from the disruption and atrophy of neurons and
glia in depression, as observed in the hippocampus [, ].
Energ y and glutathione metabolic pathways in the prefrontal
cortex were shown to be signicant biological pathways in
depressive rats []. Many studies have indicated that changes
in glutamate metabolism were associated with depression
[–]. In a stress-induced depressive mouse model, the pre-
frontal cortex in depression showed a signicant reduction of
glutamate in the GABAergic pathway, which may contribute
to depression []. Activation of metabotropic glutamate
receptor , which plays a sig nicant role in regulating the
function and cognition of the prefrontal cortex, can result
in long-term depression in the medial prefrontal cortex of
rats in vitro []. e GRINA gene, which encodes the glu-
tamatergic N-methyl-D-aspartate (NMDA) receptor subunit
epsilon- in the prefro ntal cortex, is probably disturbed in the
regulation of synaptic plasticity in depression [].
In addition, a novel miRNA (miR-b) was found to
be downregulated in depression and could decrease mRNA
and protein levels of glutamate transporter SLCA i n the
prefrontal cortex []. In addition, in the medial prefrontal
cortices of chronic unpredictable mild stress-induced depres-
sive mice, there was a downregulation of mRNAs encod-
ing proteins for the GABAergic synapses, dopaminergic
synapses, synaptic vesicle cycle, and neuronal growth and an
upregulation of miRNAs of regulating these mRN As []. In
a chronic corticosterone-mediated depressive rat model, the
majority of the related miRNAs and associated gene networks
showed glucocorticoid receptor element binding sites; this is
a potential mechanism whereby corticosterone may mediate
depression [].
ere is also a decrease in prefrontal hemodynamic
responses in depression and a signicant and positive cor-
relation between prefrontal hemodynamic responses and the
role of the emotional domain [, ]. In addition, the lack of
activation of oxygenated hemoglobin in the prefrontal cortex
indicates that it may be a mechanism of depression [].
Observing changes in hemoglobin concentration in the pre-
frontal cortex detected by near-infrared spectroscopy may b e
a convenient appro ach to evaluate and predict antidepressant
improvement in late-onset depression []. Furthermore,
increases in mean oxygenated hemoglobin may be positively
correlated with the s everity of depression [].
Repetitive transcranial magnetic stimulation of the dor-
somedial prefrontal cortex (dmPFC) and dlPFC exhibits
eectiveness and safety in treatment-resistant depression
[–]. In electroconvulsive therapy for depression, an early
decrease of intralimbic functional connectivity and a later
increase of limbic-prefrontal functional connectivity were
found []. Epidural prefrontal cortical stimulation over
the PFC has also been shown to be a promising novel
therapeutic method for treatment-resistant depression [].
Positive emotional learning can facilitate N-methyl-D-
aspartate (NMDA) receptor-dependent synaptic plasticity in
the medial prefrontal cortex and then exert positive eects on
promoting rehabilitation in depressive rats []. Some studies
have reported that NMDA receptor antagonists, such as
ketamine and lanicemine, can increase mammalian target of
rapamycin complex (mTORC) signaling by activat ing thre-
onine kinase (AKT) and extracellular signal-regulated kinase
(ERK) signaling pathways and increase synaptic number and
function in the prefrontal cortex [, , ]. A recent study
on protein level changes in the prefrontal cortex suggested
that treatment with the tricyclic antidepressant clomipramine
in neonates was a reliable model to study the eects of
antidepressants on the early phase of brain development [].
Hence, the eects of antidepressant treatment on early brain
development may induce constant pathological changes in
the prefrontal cortex. YY-, a new extractive compound,
and uoxetine can reverse the inhibitory eects of chronic
mild stress on spon taneous burst ring of medial prefrontal
cortex pyramidal neurons in depression []. Mecamylamine,
a nicotinic antagonist, is a novel antidepressant that exerts
antidepressantactionsbyincreasingPFClevelsofBDNFand
monoamines []. Interestingly, in a depressive rat model,
nut ritional supplements, such as n - polyunsaturated fatty
acids (PUFA), may prevent the development of depression
by impeding HPA axis hyperactivity []. is study suggests
that dystrophy may be another mechanism of depression.
4. Amygdalar Changes in Depression
e amygdala plays a signicant role in aective modulation
and memory encoding []. e amygdala is also a critical
site of neuronal plasticity for fear conditioning []. Mor-
phological and functional changes of the amygdala associated
with depression have been veried in many studies [, ]. In
contrast, with the hippocamp us and prefrontal cortex, stress
and depression enhance synaptic plasticity in the amygdala
and the ventral emotional network []. Stress was found to
induce dendrite retraction in the PFC and hippocampus,
while it induced dendritic arborization of pyramidal and
spiny neurons in the basolateral amygdala []. Expression of
brain-derived neurotrophic factor (BDNF), which is known
to play a central role in synapt ic plasticity induced by stress,
increased in the basolateral amygdala but decreased in the
hippocampal CA in rats [, ]. Depression disrupted
glutamate signaling at the NMD A receptor in the amygdala
in humans []. Neonatal glucocorticoid treatment enhanced
LTP response and the phosphorylation level of MAPK in the
lateral nucleus of the amygdala and promoted depression-like
behavior in adult rats [].
Amygdala kindling, as a classic model of temporal lobe
epilepsy with convulsion, can cause depression-like behaviors
in both immature rats and adult rats []. Amygdalar func-
tional connectivity diers in late-life depression phenotyp es,
and this discrepancy may be a criterion to distinguish
phenotypes of late-life depression and evaluate the severity
[].
In addition, the volume of the amygdala varied with the
severity of the depression []. Interestingly, a recent study
showed that larger gray matter volume in the bilateral
amygdala was found in rst-degree relatives of depressed
Neural Plasticity
patients []. Furthermore, amygdala perturbations caused
by negative stimuli, which elicit greater amygdala activation,
might be an early and subtle risk marker for depression [].
Recent evidence suggests t hat postpartum depression can
increase amygdalar response to infant stimuli and decrease
bilateral amygdala-right insular cortex connectivity []. e
latter may have a stimulative eec t on depression and anxiety.
However, abnormal functional connectivity in depression is
discrepant in the le amygdala []. In t he le amygdala,
the functional connectivity decreased in the amygdala pos-
itive network, while it increased in the amygdala negative
network. In a clinical study of early-childhood-onset depres-
sion, functional connectivity was reduced in the bilateral
amygdala []. Abnormal amygdala functional connectivity
is also found in late-onset depressed patients []. Hence, a
distributed neuronal network including cortical and limbic
regions rather than a discrete brain region contributes to
depression. e amygdala-associated frontolimbic circuits,
amygdala-dorsal latera l prefrontal cortex, and amygdala-
ventromedia l prefrontal cortex, which integrate aective
processes, may have characteristic dysfunctions in adolescent
depression []. ese circuits may change exponentially
in association with depression severity and potentially be
considered as a biomarker to analyze the eect of treatment
on depression. Interestingly, some of the am ygdalar changes
in depression dier by gender. A recent study indicated that
women but not men possess an IL haplotype that increases
threat-related le centromedial amygdala reactivity and
boosts susceptibility to stress-related depression by promot-
ing proinammatory responses []. Depression-associated
single-nucleotide polymorphisms can regulate the expression
of the bicaudal C homolog (BICC) gene and decrease its
promoter activity on the PKA signaling pathway in amygdalar
neurons []. ese changes may cause mood disorders.
In addition, prenatal maternal depression can inuence the
functional connectivity of the amygdala in early postnatal life,
particularly in -month-old infants [ ]. Prenatal maternal
depression can also incur the risk of aggression in ospring
[]. In contrast, many studies have suggested that amygdala
hyperactivity may improve symptoms of depression [].
Some antidepressant treatments have been shown to
playaroleinamygdalaregulation.Transcutaneousvagus
nerve stimulation is a noninvasive peripheral neuromodula-
tion therapy administered at the ear for depressed patients
andhasbeenshowntobeeectivefordepressiontreat-
ment []. It can promote amygdala-lateral prefrontal net-
work resting state functional connectivity in the right amyg-
dala of depressed patients []. Real-time fMRI neuro-
feedback training is another novel noninvasive treatment
for depression []. It can enhance blood-oxygenation-level-
dependent activity in the amygdala and benet depressed
patients. In addition, the eects of electroconvulsive therapy
in patients with depression may also be associated with
neuroplasticity changes in the amygdala, and this phe-
nomenon may be due to neurotrophic processes, including
neurogenesis []. Medication associated with the amygdala
in depressed patients includes quetiapine, cita lopram, and
ketamine [–]. In depressive rat models, the amyg-
dala has shown a signicant role in uoxetine-stimulated cell
survival and a potential to modulate antidepressant action in
hippocampal neurogenesis [].
5. Neural Plasticity in Other
Brain Regions in Depression
e ventral striatum participates in the mechanisms of natu-
ral reward, and its dysregulation contributes to symptoms of
anhedonia in depression []. Chronic stress can cause long-
term adaptations in the ventral tegmental area-accumbens
pathway that may contribute to its dysregulation in major
depression []. 𝛼
1
-Adrenoceptor dependent downregulation
of the membrane GluR subunit in the mouse ventral tegmen-
tal area mediated the depressive-like behavior induced by
lipopolysaccharide []. In rats with postpartum depression,
gestational stress could decrease dendritic length, branching,
and spine density on medium spiny neurons in the nucleus
accumbens shell and promote depressive-like behavior in the
early/mid-postpartum phase [].
Hypothalamic synaptic plasticity in depression can be
caused by increased mRNA expression of synaptotagmin I
and synapsin I, and the latter may contribute to depression-
like behaviors and HPA axis hyperactivity []. In addition,
the extracellular matrix may be involved in s ynaptic stabi-
lization and transmission and may modulate synaptic plas-
ticity in the central nervous system []. In recent studies,
modeling of bidirectional modulations in synaptic plasticity,
designed to reveal the mechanism of long-term potentia tion
and long-term depression, suggested that Ca
2+
/calmodulin
(CaM) pool size played a cr itical role in coordinat ing
LTP/LTD expression [].
6. Summary and Conclusion
Overall, neural plasticity is a vital feature of the brain in
response to intrinsic and extrinsic stimuli, including stress
and depression. Mounting clinical and basic research studies
have illuminated the correlations between neural plasticity
and depression. As the summaries in Tables and , the eects
of depression on neural plasticity are complex pathophys-
iological processes, involving multiple encephalic regions,
such as the hippocampus, prefrontal cortex, and amygdala
as well as complicated interactions of man y signal pathways,
such as NMDA, glutamate, and glucocorticoid. On the other
hand, the changes in neural plasticity induced by stress
and other negative stimuli can contribute to the onset and
development of depression. e majority of antidepressant
treatments, including psychotherapies, physiotherapies, and
medications, exert antidepress ant eects associated with neu-
ral plasticity. Unfortunately, to date, no ideal and completely
eective treatment has been found for depressed patients.
oughwehavedoneextensiveworkinthisreview,the
detailed mechanisms of neural plasticity in depression still
remain unclear. Targeting neural plasticity in depression may
lead to novel breakthroughs.
Competing Interests
eauthorsconrmthatthisarticlecontenthasnoconict
of interests.