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

1. BNST lesions aggravate behavioral despair but do not impair navigational learning in rats Pezük, Göz, Aksoy, Canbeyli Brain Research Bulletin-2006

2. 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

3. 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)

4. 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)

5. 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)

6. Sullivan 2004 Figure 1

7. 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

8. Sullivan 2004 (Figure 4)

9. Sullivan 2004 Conclusions • BNST critical link between CeA and PVN • BNST involved only in regulation of HPA axis responses to unconditioned fear/anxiety (contextual)

10. 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

11. 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

12. 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

13. 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

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

15. 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

16. Walker, Davis 1997-BLA (Fig 2) • Light-enhanced startle Mean startle amplitude Startle amp increase in bright light vs dark

17. Walker, Davis 1997-BLA (Fig 3) • Fear-potentiated startle Startle amp increases with combination of light CS and startle stimuli

18. Walker, Davis 1997-CeA (Fig 4) Startle amp greater with combination of light CS and startle stimulus than startle stimulus alone No significant effect of NBQX on light-enhanced response in CeA

19. Walker, Davis 1997-BNST (Fig 6) Illumination enhances startle NBQX infusions in BNST block light-enhanced startle independently NBQX disrupts phase 1 to phase 2 increase in startle amp

20. Walker, Davis 1997-BNST (Fig 6C) No effect seen with NBQX on fear-potentiated startle ~startle amp increased w/light

21. 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

22. 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

23. 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

24. 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

25. 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-surgeryFST • 1 week after 2nd FSTMWM • 2 weeks after MWMopen field (OF) test

26. Location (Figure 1, anterior)

27. Location (Figure 1, posterior)

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

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

30. Results-Open Field Test • Apparatus with 64 squares on floor • Explore for 5 minutes • Measure locomotor activity • No significant difference seen between experimental groups

31. 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

32. Conclusion • BNST-dissociation between depressive behavior and spatial learning • BNST involved in behavioral despair (depression), but not spatial learning