BNST lesions aggravate behavioral despair but do not

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 cueconditioned fear stimulus l G. M. Sullivan et al ¡ Neuroscience 2004

Sullivan 2004 -Intro ¡ Relay station between Ce. A and PVN l 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 l ¡ Habituation Day 1: training l l 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 l ¡ Lesion Ce. A or BNST (sham) Day 8: cue vs. context testing l Place rats in experimental cage, measure freezing (camera) or corticosterone (decapitation/collection of trunk blood)

Sullivan 2004 Figure 1

Sullivan 2004 -Results ¡ ¡ In Ce. A, 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 l No role in freeze/cort responses to tone

Sullivan 2004 (Figure 4)

Sullivan 2004 Conclusions BNST critical link between Ce. A 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 l 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 (bl. A), central Amygdala (Ce. A), and BNST ¡ Use AMPA-R antagonist (NBQX) or PBS ¡

Walker, Davis 1997 -Previous Findings BLA lesions disrupt conditioned fear responses ¡ Ce. A lesions disrupt individual fear behaviors ¡ BNST lesions disrupt unconditioned fear ¡ l BNST and Ce. A receive inputs from BLA ¡ BLA conditioned and unconditioned fear

Walker, Davis 1997 -Experiment Test bl. A, Ce. A, and BNST in fearpotentiated startle (cond. ) and light -enhanced startle (uncond. ) ¡ Intracranial infusions of AMPA-R antagonist (NBQX) into bl. A, Ce. A, BNST ¡

Walker, Davis 1997 (Figure 5) Cannula tip placements in BNST

Walker, Davis 1997 -Results ¡ ¡ ¡ NBQX in BLA disrupt both behaviors NBQX in Ce. A only blocked fearpotentiated startle NBQX in BNST only blocked lightenhanced 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 -Ce. A (Fig 4) No significant effect of NBQX on light-enhanced response in Ce. A 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 6 C) No effect seen with NBQX on fearpotentiated startle ~startle amp increased w/light

Walker, Davis 1997 Conclusions ¡ ¡ BLA sensory center in light-enhanced startle response Ce. A control center of fear-potentiated startle BNST role in light-enhanced startle response Double dissociation between BNST and Ce. A 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 l Pezük, Göz, Aksoy, Canbeyli ¡ Brain Research Bulletin-2006

Introduction ¡ BNST lesions can aggravate behavioral despair l ¡ ¡ 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 l 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 -275 g) 12/12 h light/dark cycle (lights on @ 0700) Stereotaxic surgery (electrolytic lesions) 14 BNST-lesioned and 8 sham 2 weeks post-surgery FST 1 week after 2 nd FST MWM 2 weeks after MWM open field (OF) test

Location (Figure 1, anterior)

Location (Figure 1, posterior)

Results-Forced Swim Test Figure 2 * Increased immobility in BNST-lesioned animals

Results-Morris Water Maze Figure 3 No difference seen between experimental groups

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 l BNST involved in behavioral despair (depression), but not spatial learning