BNST lesions aggravate behavioral despair but do not impair navigational learning in rats

Pezük, Göz, Aksoy, Canbeyli Brain Research Bulletin-2006

Episode I: The Phantom Nucleus

Lesions in the BNST disrupt corticosterone (B) and freezing responses elicited by a contextual but not by a specific cue-conditioned fear stimulus G. M. Sullivan et al

Neuroscience 2004

Sullivan 2004-Intro

Relay station between CeA and PVN Control of HPA response to conditioned

fear stimulus in context Behavioral and neuroendocrine

Cue: simple sensory stimulus (tone) Context: complex environmental

representation (no tone)

Sullivan 2004-Experiment

Day 0 Habituation

Day 1: training Cue: tone (CS) paired with footshock

(US) in home cage Contextual: rats placed in experimental

cage, footshock (US) applied w/out specific cue (CS)

Sullivan 2004-Experiment

Day 3: surgery Lesion CeA or BNST (sham)

Day 8: cue vs. context testing Place rats in experimental cage,

measure freezing (camera) or corticosterone (decapitation/collection of trunk blood)

Sullivan 2004

Figure 1

Sullivan 2004-Results

In CeA, bilateral lesions after training block expression of freezing and cort responses to cue and context

In BNST, lesions only block freezing and cort responses to context No role in freeze/cort responses to tone

Sullivan 2004 (Figure 4)

Sullivan 2004 Conclusions

BNST critical link between CeA and PVN

BNST involved only in regulation of HPA axis responses to unconditioned fear/anxiety (contextual)

Episode II: Attack of the Amygdala

Double Dissociation between the Involvement of the Bed Nucleus of the Stria Terminalis and the Central Nucleus of the Amygdala in Startle Increases Produced by Conditioned versus Unconditioned Fear David Walker, Michael Davis

The Journal of Neuroscience 1997

Walker, Davis 1997-Intro

Compare startle response to light (light-enhanced) or previously paired shock (fear-potentiated)

Examine basolateral Amygdala (blA), central Amygdala (CeA), and BNST

Use AMPA-R antagonist (NBQX) or PBS

Walker, Davis 1997-Previous Findings

BLA lesionsdisrupt conditioned fear responses

CeA lesionsdisrupt individual fear behaviors

BNST lesions disrupt unconditioned fear

BNST and CeA receive inputs from BLA BLAconditioned and unconditioned fear

Walker, Davis 1997-Experiment

Test blA, CeA, and BNST in fear-potentiated startle (cond.) and light-enhanced startle (uncond.)

Intracranial infusions of AMPA-R antagonist (NBQX) into blA, CeA, BNST

Walker, Davis 1997 (Figure 5)

Cannula tip placements in BNST

Walker, Davis 1997-Results

NBQX in BLAdisrupt both behaviors

NBQX in CeAonly blocked fear-potentiated startle

NBQX in BNSTonly blocked light-enhanced startle

Walker, Davis 1997-BLA (Fig 2)

Light-enhanced startle

Mean startle amplitude

Startle amp increase in bright light vs dark

Walker, Davis 1997-BLA (Fig 3)

Fear-potentiated startle

Startle amp increases with combination of light CS and startle stimuli

Walker, Davis 1997-CeA (Fig 4)

No significant effect of NBQX on light-enhanced response in CeA

Startle amp greater with combination of light CS and startle stimulus than startle stimulus alone

Walker, Davis 1997-BNST (Fig 6)

Illumination enhances startle

NBQX disrupts phase 1 to phase 2 increase in startle amp

NBQX infusions in BNST block light-enhanced startle independently

Walker, Davis 1997-BNST (Fig 6C)

No effect seen with NBQX on fear-potentiated startle

~startle amp increased w/light

Walker, Davis 1997 Conclusions

BLAsensory center in light-enhanced startle response

CeAcontrol center of fear-potentiated startle

BNSTrole in light-enhanced startle response

Double dissociation between BNST and CeA in response to light-enhanced and fear-potentiated startle

Episode III: Revenge of the BNST

BNST lesions aggravate behavioral despair but do not impair navigational learning in rats Pezük, Göz, Aksoy, Canbeyli

Brain Research Bulletin-2006

Introduction

BNST lesions can aggravate behavioral despair Effects of behavioral despair on cognitive

function unknown BNST involved in autonomic,

neuroendocrine, and motivational responses to stress

BNST modulates HPA axis response to stress Effects on memory and learning

Hypothesis

Animals with BNST lesions will show impaired performance in navigational learning tasks (Morris Water Maze)

Impaired acquisition of navigational learning in BNST-lesioned animals

Materials/Methods

Male Wistar rats (260-275g) 12/12h light/dark cycle (lights on @ 0700) Stereotaxic surgery (electrolytic lesions) 14 BNST-lesioned and 8 sham 2 weeks post-surgeryFST 1 week after 2nd FSTMWM 2 weeks after MWMopen field (OF) test

Location (Figure 1, anterior)

Location (Figure 1, posterior)

Results-Forced Swim Test

*

Increased immobility in BNST-lesioned animals

Figure 2

Results-Morris Water Maze

No difference seen between experimental groups

Figure 3

Results-Open Field Test

Apparatus with 64 squares on floor Explore for 5 minutes Measure locomotor activity No significant difference seen

between experimental groups

Discussion

BNST lesions cause longer periods of immobility in Forced Swim Test

BNST lesions have no effect on navigational learning (MWM)

BNST-role in depression BNST-learning during stressful

situations

Conclusion

BNST-dissociation between depressive behavior and spatial learning BNST involved in behavioral despair

(depression), but not spatial learning