Adamec, Mervis (2012) Behav Brain Res PDF

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Behavioural Brain Research 226 (2012) 133–146

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Behavioural Brain Research

journal homepage: www.elsevier .com/ locate /bbr

Research report

Dendritic morphology of amygdala and hippocampal neurons in more and lesspredator stress responsive rats and more and less spontaneously anxioushandled controls

Robert Adamec a,∗, Mark Heberta, Jacqueline Blundella, Ronald F. Mervis b,c

a Memorial University, St. John’s, Newfoundland, Canada, A1B 3X9b Center of Excellence for Aging and Brain Repair, Department of Neurosurgery and Brain Repair, University of South Florida College of Medicine, Tampa, FL 33612,USAc Neurostructural Research Labs, Inc., 12409 Telecom Drive, Tampa, FL 33637,USA

a r t i c l e i n f o

Article history:

Received 28 July 2011

Received in revised form 2 September2011

Accepted 4 September 2011

Available online xxx

Keywords:

Stress

Amygdala

Hippocampus

Morphology

Resilience

Vulnerability

a b s t r a c t

We investigated the neurobiological bases of variation in response to predator stress (PS). Sixteen days

after treatment (PS or handling), rats were grouped according to anxiety in the elevated plus maze (EPM).

Acoustic startle was also measured. We examined the structure of dendritic trees of basolateral amygdala

(BLA) output neurons (stellate and pyramidal cells) and of dorsal hippocampal (DHC) dentate granule

cells of less anxious (LA) and more (extremely) anxious (MA) stressed animals (PSLA and PSMA). Handled

controls (HC) which were less anxious (HCLA) and spontaneously more anxious (HCMA) equivalently to

predator stressed subgroups were also studied. Golgi analysis revealed BLA output neurons of HCMA

rats exhibited longer, more branched dendrites with higher spine density than the other groups of rats,

which did not differ. Finally, spine density of DHC granule cells was equally depressed in HCMA and PSMA

rats relative to HCLA and PSLA rats. Total dendritic length of BLA pyramidal and stellate cells (positive

predictor) and DHC spine density (negative predictor) together accounted for 96% of the variance of

anxiety of handled rats. DHC spine density was a negative predictor of PSMA and PSLA anxiety, accounting

for 70% of the variance. Data are discussed in the context of morphological differences as phenotypic

markers of a genetic predisposition to anxiety in handled controls, and a possible genetic vulnerability to

predator stress expressed as reduced spine density in the DHC. Significance of findings for animal models

of anxiety and hyperarousal comorbidities of PTSD are discussed.

© 2011 Elsevier B.V. All rights reserved.

1. Introduction

Individuals respond to stress and trauma differently. In some,

traumatic experience leadsto posttraumatic stress disorder (PTSD)

while others are less affected [1–3]. Relatively little is known about

the molecular and neural substrates of individual differences in

response to trauma [1]. However, correlational behavioral research

implicates a variety of factors, including personality traits [4,5] as

well as interaction of genetic factors and experiential factors, suchas reducedfunctioningpolymorphisms in theserotonin transporter

(5-HTTLPR), and life stress or social support at the time of stress

Abbreviations: BLA, basolateral amygdala; DHC, dorsal hippocampus; EPM,

elevated plus maze; HC, handled control; 5-HTTLPR, reduced functioning polymor-

phisms in the serotonin transporter; LA, less anxious; MA, more anxious; mRNA,

messenger RNA; PS, predator stressed; PSS, predator scent stressed; PTSD, post

traumatic stress disorder.∗ Corresponding author at: Department of Psychology, Memorial University, St.

John’s, NL, Canada, A1B 3X9. Tel.: +1 709 737 7671; fax: +1 709 864 2430.

E-mail address: [email protected] (R. Adamec).

[6–8]. Moreover,the 5-HTTLPRexerts a potent modulatory effect on

amygdala reactivity to environmental threat [6]. Since this geneti-

cally driven effect exists in healthy subjects, Hariri and colleagues

suggest that the 5-HTTLPR mayrepresent a susceptibility factor for

affectivedisorders by biasing the functional reactivity of thehuman

amygdala in the context of stressful life experiences and/or defi-

cient cortical regulatory input [6]. Supportfor this idea comes from

studies associating PTSD with 5-HTTLPR [8–13]. So, factors affect-

ing functional amygdala reactivity may be important contributorsto vulnerability to stress. In this context, it is important to note

that right amygdala reactivity to both trauma reminders and gen-

eral negative stimuli is enhanced in humans diagnosed with PTSD

[14,15].

One way to identify putative causal substrates is to study the

effects of stress on brain and behavior of more and less stress vul-

nerable animals. A useful paradigm in this regard is exposure of

rodents to brief predator stress, a putative model of hyperarousal

and generalized anxiety characteristics of PTSD [16–18]. Domes-

ticated strains of laboratory rats retain the fear of predators like

a cat, even if they have never been exposed to predators [19,20].

0166-4328/$ – seefrontmatter © 2011 Elsevier B.V. All rights reserved.

doi:10.1016/j.bbr.2011.09.009

http://localhost/var/www/apps/conversion/tmp/scratch_4/dx.doi.org/10.1016/j.bbr.2011.09.009http://localhost/var/www/apps/conversion/tmp/scratch_4/dx.doi.org/10.1016/j.bbr.2011.09.009http://www.sciencedirect.com/science/journal/01664328http://www.elsevier.com/locate/bbrmailto:[email protected]://localhost/var/www/apps/conversion/tmp/scratch_4/dx.doi.org/10.1016/j.bbr.2011.09.009http://localhost/var/www/apps/conversion/tmp/scratch_4/dx.doi.org/10.1016/j.bbr.2011.09.009mailto:[email protected]://www.elsevier.com/locate/bbrhttp://www.sciencedirect.com/science/journal/01664328http://localhost/var/www/apps/conversion/tmp/scratch_4/dx.doi.org/10.1016/j.bbr.2011.09.009


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136 R. Adamecet al./ Behavioural Brain Research 226 (2012) 133–146

Fig.1. (A)A photomicrographof a Golgistainedstellate cellof thebasolateralamyg-

dala(BLA).(B) A photomicrographof a Golgistainedpyramidal cellof thebasolateral

amygdala (BLA).

cells were selected from thegranule cell layer of theDHC. These cells haddendritic

trees extendingclearly intothe molecular layer. Fig. 2A containsa photomicrograph

of a Golgi stained dentate granule cell in theDHC. Fig. 2B contains two examples of

dentate dendritic spinesfrom HCLA and HCMA rats.

Allselected neurons hadto meet certain criteria:theyhadto bewell stained and

they hadto havebranches whichwere unobscuredby otherneurons, glia,blood ves-

sels, orprecipitate.For theanalysisof dendriticbranching andlength,all theselectedneurons had to be located in the middle third of the thickness of the section. This

was done toavoidevaluatingneuronswhich– iflocatedtoo superficiallyor toodeep

within the thickness of the section – may have had too many branches foreshort-

ened. Foreach subject andfor each BLAcell type, three neurons were selected from

the right hemisphere and three neurons were selected from the left hemisphere

for analysis. For the dentate four neurons were selected from each hemisphere for

analysis.

In summary, forBLA stellate cells,from each brain,we evaluatedthreeneurons

from each hemisphere – a total of 6 stellate cellsper brain. Similarly, for the pyra-

mids, we also evaluated 6 neurons per brain. A total of 25 brains were used. Of a

possible total of 6×2×25= 300 neurons in the study, due to staining issues, three

brains wereeach oneneuronshort,so a totalof 297BLA neuronswere evaluated.The

brains missing cells were HCMA right hemisphere missing a pyramidal cell; HCLA

left hemisphere missing a pyramidalcell; HCLA right hemisphere missing a stellate

cell. Forthe dentate granule cells we evaluatedfour neurons from each hemisphere

– a total of 8 dentate cells per brain. A total of 20 brains were used (5 rats from

each of four groups), these were rats with DHC sections containing granule cells in

Fig. 2. (A) A photomicrograph of a Golgi stained dentate granulecell of the dorsal

hippocampus. (B) Photomicrograph of Golgi stained dentate granule cell spines of

the dorsal hippocampusof a handled less anxious (HCLA top) rat and of a handled

more anxious (HCMA bottom) rat.


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Fig. 4. Plotted in (A and B) are mean+SEM of behaviors in the hole board for all

handled controls (HC) and all predator stressed rats (PS). (A) shows mean+ SEM of

measures of exploration (head dips) and activity (rears) in the hole board test. (B)

shows mean+ SEM of time spent in the centerand timespent near the walls of the

hole board. Within a given behavioral plot in (A and B), means marked differently

differ and unmarked means do notdiffer.

F (1,299)≥23.67 all p < .001). Consistent with this analysis, there

were no group differences in the hole board measures of activ-

ity/exploration (rears or head dips, Fig. 4A). However, stressed rats

spent more time near thewalland less time in the centerof the hole

board (Fig. 4 B, all F (1,300)≥5.86, p < .02). This is consistent with

the anxiety data in the EPM. Taken together these data support the

conclusion that PS rats as a group were selectively more anxious in

the EPM than handled controls.

3.2. LA – PS and HC, and MA – PS and HC animals show

equivalent levels of anxiety in the EPM 2 weeks after treatment

Behavior of rats selected for Golgi analysis was analysed using

two way ANOVA for Stress (HC and PS) and Anxiety Level (LA, MA).

There wasa main Anxiety Level effectfor anxiety scores in the EPM

(Fig. 5A, F (1,21) = 233.71, p < .0001). There was no Stress or Stress

by Anxiety Level interaction (all F (1,21)≤ .05, p > .80). So PSMA and

HCMA rats displayedequal anxiety scores whichwere greater than

the anxiety scores of PSLA and HCLA rats, which did not differ.

There was a Stress effect for closed arm entries in which PS rats

entered the closed arms less frequently than did HC rats (Fig. 5B,

F (1,21) = 10.70, p .22; Fig. 5B) suggesting

reduced locomotor activity/exploration in the EPM in stressed rats.

To assess if locomotor activity/exploration contributed to Anxiety

Fig.5. (A)Plottedaremean+ SEM ofthe anxiety indexof less anxious (LA– less EPM

anxiety) and moreanxious (MA – more EPManxiety)ratsselected forGolgi analysis

in the Handled Controls and Predator Stressed groups. Means marked similarly do

notdifferwhilemeansmarkeddifferentlydiffer.(B) Plottedare mean+ SEMof closed

arm entries in the EPM of less anxious (LA – less EPM Anxiety) and more anxious

(MA – more EPM anxiety) rats selected for Golgi analysis in the Handled Controls

and Predator Stressed groups. In this plot means marked differently differ, means

marked the same do not differ. (C). Plotted are mean+SEM of the anxiety index

of less anxious (LA – less EPManxiety)and more anxious (MA– more EPManxiety)

rats selectedfor Golgianalysis inthe HandledControlsand PredatorStressedgroups.

Means arethoseobserved after theinfluenceof closedarm entries is removed with

analysis of covariance. Means marked similarly do not differ while means marked

differently differ.


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R. Adamec et al./ Behavioural Brain Research 226 (2012) 133–146 139

Level differences in anxiety scores, closed arm entries were used

as a covariate in a reanalysis of anxiety scores. Reduced locomotor

activity/exploration in the EPM did not contribute to anxiety score

differences, as the original pattern of Anxiety Level differences

was preserved in the analysis of covariance (Fig. 5C, Anxiety Level

effect, F (1,20) = 205.54 p < .0001; Stress effects and interaction all

F (1,20)≤ .17, p > .69). There were no effects in theanalysis of behav-

iors in the hole board test (F (1,21)≤0.79, p > .05). Together these

data support the conclusion that MA rats as a group (PS +HC) were

selectively and equally more anxious in the EPM than LA rats as a

group (PS+ HC), which were selectively and equally less anxious.

3.3. LA, MA – HC rats show a different pattern of startle response

than LA, MA PS rats 2 weeks after treatment

Peak startle amplitudes were not normally distributed

(Omnibus test 694.62, p < .001). So LA and MA HC rats and LA

and MA PS rats were compared in a one way non parametric

Kruskal–Wallis ANOVA on median peak startle amplitudes. Groups

differed (2(3) = 35.43, p >.01; Fig. 6A) such that HCMA rats andPSLA and PSMA rats showed greater peak startle amplitudes than

HCLArats. MoreoverHCMA ratsequaledPSLA andPSMA rats,which

did not differ (Kruskal–Wallis multiple Z test, p < .01).

Rate of habituation (Tau – the trial constant) was calculated asdescribedin the methods section. Allfits to theexponentialdecline

functionwere good(all degrees of freedom adjusted r 2 >.505 13.78 p < .001, all > 0, p < .01).The estimateof Tau included a standard error of estimate. These standard errors

were used to calculate t-statistics between the trial constants of

the different groups. Planned comparisons of the Tau estimates

between groups were done using two-tailed t tests. Like peak star-

tle amplitudes, HCMA rats andPSLA and PSMA rats showedgreater

Tau values (more prolongedhabituation)than HCLA rats.Moreover

HCMA rats equaled PSLA andPSMAratswhichdid not differ(Fig.6B,

two tailed t tests, all t (58)≥2.66, p < .01).

3.4. The predator stress experience

LA and MA predator stressed rats were compared with respect

to cat response to them and their responses to the cat. There were

no group differences (allF (1,5)≤ .75, p > .43). Thereforethe predator

stress experience, as measured, did not differ between LA and MA

predator stressed rats.

3.5. Dendritic morphology of BLA neurons – total dendritic length

BLA stellate and pyramidal principle output neurons of the

groups differed in total dendritic length (all F (3,21)≥3.63, p


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Fig.7. Plotted aremean+ SEMof totaldendritic length(mM)collapsedacrosshemi-

spheres. Plotted separately are Handled Controls which are less anxious (HCLA) or

more anxious (HCMA) and Predator Stressed rats which are less anxious (PSLA) or

moreanxious(PSMA). (A) shows datafrom basolateral amygdala stellate cellswhile

data from pyramidal cells appear in (B). For a given plot (A or B) means marked

similarly do not differ, while means marked differently differ.

showed elevated spine densities on pyramidal cell dendrites (basi-

lar and apical combined, there being no effects of type of dendritic

segment). Moreover, HCMA rat spine density was greater than all

other groups, whichdid not differ (Fig. 11A, all t (21)≥2.08, p


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Fig. 9. Plotted are mean shell crossings vs distance from the soma of the crossingsfrom the Sholl analysis of basolateral amygdala pyramidal cells collapsed across

hemispheres.Plottedseparatelyare HandledControlswhich areless anxious (HCLA)

or more anxious (HCMA) and Predator Stressed rats which are less anxious (PSLA)

or more anxious (PSMA). (A) shows mean±SEM, while (B)showsmean±95% con-

fidence intervals of shell crossings. In (B), HCMA means marked with an “*” differ

from the remaining groups which do not differ. This occurs over a range from the

soma of 40–90M.

greater anxiety. Therewere no correlations of dendritic length with

anxiety or peak startle amplitude in PS rats (all r ≤ .47, p >.10).

3.11.2. BLA mean number of dendritic branches correlations with

behavior

There were no correlations with behavior (anxiety or peak star-tle amplitude) of branches in pyramidal or stellate cells of HC or PS

rats (all r ≤ .47, p > .10). So dendritic complexity in the BLA did not

predict behaviors measured here.

3.11.3. BLA spine density correlations with behavior

Spine density didcorrelate with anxiety butnot startle. Thecor-

relationwas between anxietyand spine densityon pyramidal apical

dendrites of HCMA and HCLA rats (r = .51, p < .04). The positive cor-

relationindicates thatgreater spinedensitypredicts higher levels of

anxiety. There were no correlations of spine density with behavior

on basilar dendrites of HCMA and HCLA rats, nor were there corre-

lations with behavior of apical and basilar dendriticspine densities

of PSMA and PSLA rats (all r ≤ .36, p < .24).

Fig. 10. Plotted aremean+ SEMof numberof branches in thebranch point analysiscollapsedacrosshemispheresand branch order.Plottedseparatelyare HandledCon-

trols which areless anxious (HCLA)or more anxious (HCMA)and Predator Stressed

rats which are less anxious (PSLA) or more anxious (PSMA). (A) shows data from

basolateral amygdala stellatecells whiledata frompyramidalcells appear in (B).For

a given figure (A or B) means marked similarly do not differ, while means marked

differently differ.

3.12. Dendritic morphology of DHC dentate neurons – total

dendritic length

There were no group effects or interactions with hemisphere

for total dendriticlength of dentate granule cells. Averagedover all

rats, the dendritic length equaled 2076.3±37.5M.

3.13. Dendritic morphology of DHC dentate neurons – Shollanalysis

The Sholl analyses were consistent with the total den-

dritic length analyses. There were no Group or Group (HCLA,

HCMA, PSMA, PSLA) x shell interactions (F (3,16) = .72, p >.55;

F (99,528)= .83, p > .87).

3.14. Dendritic morphology of DHC dentate neurons – branch

point analysis

There were no group effects of mean total branches

(F (3,16) = 0.97, p > . 42) or group by branch order interactions

(F (3,15) = 1.41, p > .26; F (15,75)= .92, p > .54) for dentate granule

cells.


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Fig. 11. (A) Plotted are mean+ SEM of spine densities (spines/M) of basolateral

amygdala pyramidal cells collapsed across hemispheres and basilar and apicalden-

drites. Plotted separately are Handled Controls which are less anxious (HCLA) ormore anxious (HCMA) and Predator Stressed rats which are less anxious (PSLA) or

more anxious (PSMA). Means marked similarly do not differ, while means marked

differently differ.

(B) Plotted are mean+ SEM of total dendritic length (M) of basolateral amygdala

stellateand pyramidalcells combined fromthe righthemisphere.Plottedseparately

are Handled Controls which are less anxious (HCLA) or more anxious (HCMA) and

PredatorStressed ratswhich areless anxious (PSLA) or moreanxious(PSMA).Means

marked similarly do not differ, while means markeddifferently differ.

3.15. Dendritic morphology of DHC Dentate neurons – spine

density analysis

Dueto non normality ofthe data (Omnibus test = 34.58, p < .001),

DHC spine density was analysed comparing group medians with

Kruskal–Wallis non parametric analysis of medians. Median con-trasts were done using the Kruskal–Wallis multiple Z test ( p


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sine) was used to correlate independent variables (dendritic mor-

phology) with anxiety. The criteria for a successful model included

a significant multiple R, and all coefficients of independent vari-

ables being significantly different from zero. The correlation was

done on HC rats (across HCMA and HCLA). The first model tested

included all three independent variables. Two of three coeficients

of independent variables were significantly different from zero

(−2.54 = t (7) = 2.54, p < .04) and multiple R was significantly differ-

ent from zero (F (3,7) = 62.3, p


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and behavior in PS rats. In HC rats, anxiety correlated positively

with total dendritic length of pyramidal and stellate cells. There-

fore in HC rats longer dendrites predict greater anxiety. In contrast

there were no correlations with behavior (anxiety or peak startle

amplitude) of branches in pyramidal or stellate cells of HC rats.

So dendritic complexity did not predict behaviors measured here.

On the other hand, spine density on pyramidal apical dendrites of

HCMA and HCLA rats correlated positively with anxiety but not

startle amplitudes. Thus greater excitatory spine density [56] pre-

dicts higher levels of anxiety.In contrast, there wereno correlations

of spine density with behavior on basilar dendrites of HCMA and

HCLA rats.

4.3. Golgi findings – dorsal hippocampus dentate granule cells

There were no groupdifferencesbetween HC and PS rats in total

dendritic length or branching of dentate granule cells. However,

more anxious PS and HC rats displayed equally reduced spine den-

sity on granule cell dendrites relative to less anxious PS andHC rats

(Fig. 12). Moreover, across PS and HC rats, spine density correlated

negatively with anxiety, but not startle, suggesting fewer dendritic

spines predict more anxiety.

Functionally,reducedspines would be associatedwith less exci-

tatory activity in the trisynaptic circuit of the dorsal hippocampus.This might make sense in view of dorsal hippocampus projections

to the medial prefrontal cortex [58]. This circuit whenexcited could

exert an inhibitory influence on BLA and central amygdala (CeA)

excitability via medial prefrontal cortex excitatory projections onto

inhibitory intercalatednucleus neurons in the amygdala[59]. If this

surmise is true, one would predict thatin LA PS rats there would be

more mPFC output cellular activation during predator stress, and

conversely in MA PS rats there would be less mPFC cellular activa-

tion during predator stress. This is in fact the case (Adamec et al.,

accepted).

Since HC rats display thesespinedifferences, they likelyreflect a

spontaneouslyoccurring and perhaps genetically determined mor-

phological feature. In viewof thispossibility,the samemightbe said

of the PS rats. If true, then a bias toward more dorsal hippocampalactivation in PSLA rats would suppress BLA and CeA excitabil-

ity and reduce BLA plasticity in response to stress. The opposite

would be the case for PSMA rats, where reduced dorsal hippocam-

pal activation would relieve medial prefrontal cortical suppression

of the amygdala and promote more BLA plasticity in response to

stress. This is an attractive hypothesis from a translation perspec-

tive, where smaller human hippocampal volume is a vulnerability

marker for PTSD [38].

4.4. Robust correlation and multiple correlation analyses of BLA

and hippocampal morphology with behavior

Multiple correlation of BLA and DHC morphology variables

distinguishing the groups was done on HC rats (across HCMAand HCLA). The multiple correlation of dentate cells spine den-

sities and dendritic lengths of BLA stellate and pyramidal cells

combined yielded a satisfactory model of the following form: Anx-

iety=−1.19×dentate cells spine densities + 2.12×BLA pyramidal

and stellate cells total dendritic lengths (summed). Coefficients

were standardized and differed from zero and the multiple R was

significantly different from zero. These two variables accounted for

96.2% of the variance of anxiety (df adjusted R2 = .962). The model

indicates that lower DHC dendritic spine densities predict more

anxiety while greater BLA dendritic lengths predict more anxiety.

Itis strikinghow much of the variance of anxiety is accountedfor by

these two variables, which together account for much of the anx-

iety seen in HCMA and HCLA rats. As suggested above, the HCMA

phenotype likely reflects an underlying genotype, and present data

strongly implicate BLA dendritic hypertrophy and dentate spine

density reduction as the neural expression of the phenotype. The

modelsuggests dendritichypertrophy in BLA principle output neu-

rons increases BLA excitability. Moreover reduced excitability in

the trisynaptic circuit of the DHC likely adds to this excitability

by reducing hippocampal driving of a negative feedback from hip-

pocampal to medial prefrontal cortex to amygdala projections (see

above). Together this increase in BLA excitability produces more

anxiety in HCMA rats. Conversely reduced BLA dendritic lengths

and increased DHC dentate spine density produces less anxiety in

HCLA rats.

For PSMA and PSLA a robust correlation was done using hip-

pocampal spine densities alone. The correlation of dentate cells

spine densities yielded a satisfactory model of the following form:

Anxiety =−0.86×dentate cells spine densities. The coefficient is

standardized and differs from zero and R was significantlydifferent

from zero. This variable accounted for 70.4% of the variance of anx-

iety (df adjusted R2 = .704). If spine density is decreased by stress,

then the reduced driving of the dorsal hippocampus may serve to

prolong anxiety by increasing BLA response to subsequent stress.

If spine density is a phenotypic marker of vulnerability to stress,

its presence alone does not alter anxiety but by relieving negative

cortical feedback during stress enhances BLA excitability changes

in response to predator stress.

4.5. Conclusions

Our findings implicate variation in dendritic arbor of amygdala

neurons as a candidate mechanism for variation in anxiety but not

startle in spontaneously more and less anxious rats. Correlation

analysis suggests that dendritic length is particularly relevant to

anxiety levels. It is surprising that the same cannot be said of vari-

ation in anxiety of stressed rats. The BLA can undergo structural

reorganization in response to stressors as diverse as immobi-

lization, maternal stress and external application of the stress

hormone,corticosterone [32,34,60,61]. A prominent feature of such

structural reorganization is dendritic expansion (hypertrophy) of

excitatory neurons of the BLA. Once evoked, BLA hypertrophy isas lasting as long-lasting anxiety [33]. Conversely, dendritic retrac-

tion achieved by viral-mediated over expression of inhibitory SK2

potassium channels in BLA results in reduced anxiety [35]. Clearly

predator stress is not a stressor which induces dendritic hyper-

trophy. Therefore, dendritic remodeling of BLA by stress seems to

be stressor specific. This is consistent with earlier work of Vyas

and colleagues [32]. This raises a caution regarding translation of

findings in animal models of stress vulnerability/resilience. While

morphological characteristics of amygdala cells are a putative sub-

strate for individual differences in response to stress, there are

other possibilities. So effects of a variety of stressors on brain and

behavior should be examined to categorize candidate mechanisms.

It is an open question if different stressors impact limbic circuits in

humans differently.In contrast,spine density of DHC dentate granule cells is a nega-

tive predictor of anxiety in both handled (HCMA and HCLA) and

predator stressed (PSMA and PSLA) rats. This either means that

predator stress reduces spine density on DHCdentate granule cells,

or giventhe spontaneousreduction of spine densitiesin HCMA rats,

representsa preexisting phenotype. If the latter, reduced DHC spine

densities represents a vulnerability factor in anxious response to

predator stress. From our present data, it is difficult to determine

if morphimetric differences between MA and LA stressed animals

werestress induced,or werepre-existingdifferences.It is notpossi-

ble to achieve paired measurements before andafter stress, because

of the post-mortem nature of Golgi staining. Nor is it yet possible

to reliably predict MA or LA responses to predator stress. So test

of whether reduction in dendritic spine density of dentate granule


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