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 lesions  disrupt conditioned fear responses  CeA lesions  disrupt individual fear behaviors  BNST lesions  disrupt unconditioned fear BNST and CeA receive inputs from BLA  BLA  conditioned 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 BLA  disrupt both behaviors  NBQX in CeA  only blocked fear- potentiated startle  NBQX in BNST  only 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  BLA  sensory center in light-enhanced startle response  CeA  control center of fear-potentiated startle  BNST  role 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 ( g)  12/12h light/dark cycle (lights 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 * 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