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The integrated bnst

The Story of BNST Function and Influence. The integrated bnst. I. What is the BNST.  A. Part of the extended Amygdala Bilaterally  B. Relay Station – Bridge 1. from Limbic + PF Corticies a. Amygdala b. Hippocampus 2. to the PVN. I. What is the BNST.

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The integrated bnst

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  1. The Story of BNST Function and Influence The integrated bnst

  2. I. What is the BNST •  A. Part of the extended Amygdala • Bilaterally •  B. Relay Station – Bridge • 1. from Limbic + PF Corticies • a. Amygdala • b. Hippocampus • 2. to the PVN

  3. I. What is the BNST  C. Positively/Negatively regulates Stress D. +/- regulates Anxiety E. +/- regulates Autonomic function F. Important implications for Gender and Reproduction 1. Sex differences

  4. Deep to the Parietal Cortex • Enclosed by: • Lateral ventricle • lateral septum • Fornix • Nucleus accumbens • Preoptic area (POA) • Hypothalamus II. Where is the BNST

  5. Lateral to Anterior Commissure • Inferior to Lateral Ventricle • Medial to Internal Capsule • And lateral septum • Fornix • Nucleus accumbens • POA • Superior to hypothalamus II. Where is the BNST

  6. In the amygdalar complex • Medial to BLA (basolateral amygdala) • Inferior to CeA (central amygdala) • Superior to MeA (medial amygdala) II. Where is the BNST

  7. II. Where is the BNST

  8. II. Where is the BNST

  9. II. Where is the BNST Ant Comm

  10. II. Where is the BNST Ant Comm

  11. II. Where is the BNST

  12. Anterior BNST • avBNST • Includes dmBNST • Includes fuBNST • laBNST, maBNST, daBNST • Boundaries of Anterior BNST? III. Subdivisions of the BNST

  13. III. Subdivisons of the BNST B. posterior C. lateral 1. dlBNST, vlBNST D. medial 1. amBNST

  14. III. Subdivisions of the BNST Lateral Ventricle Internal Capsule Dorsal Lateral Anterior Lateral Juxtacapsular Anterior Medial Posterior Lateral Ventral Medial Ventral Lateral Parastrial Anterior Commissure

  15. IV. inputs to BNST • Major Input from Central Amygdala • CeA to vlaBNST – GABA • CeA to avBNST - CRF • MeA to prBNST – GABA • Other Amygdala?

  16. IV. Inputs to BNST • Infralimbic PFC – Glu to dm/fusBNST • Hippocampus to BNST - Glu • vSubiculum – Glu to prBNST • PFC-Limbic projections onto inhibitory GABA neurons in BNST • Counters stimulatory input from amygdala • to mpPVN CRF cells

  17. LC to avBNST – NE/a2 • A1 & A2 to avBNST – NE/a2 • DbH colocalized in BNST with ERa • VTA to BNST – DA/D1,2? • dRaphe to aBNST • 5-HT/5-HT1A, 1B,2A,7? • N Sol tract to avBNST – ? • Cerebellum IV. Inputs to BNST – Brainstem Regions

  18. V. Projections from BNST • 1o output from BNST is to PVN • GABA from lBNST, aBNST, pBNST to mpPVN (CRF cells) • CRF • Glu from avBNST to mpPVN

  19. IV-V. Inputs to/projections from BNST Choi, D. C. et al. J. Neurosci. 2007;27:2025-2034

  20. vlBNST projects to VTA (reward) • CRF • other places? V. Projections from the BNST - Brainstem

  21. mBNST to N. of the Solitary Tract • CRF • mBNST projects to caudal vl medulla • mBNST dorsal N of the Vagus (dV) • Autonomic control • Connections from PVN to brainstem too V. Projections from the BNST - Brainstem

  22. Direct projections to the pons • Relay station to relay station • Stress relay to Cerebellar relay • Link to cerebellar eye blink circuit V. Projections from the BNST - Brainstem

  23. HPA Axis Stimulation • Direct • avBNST stimulated by CRF from CeA • To Glu and CRF cells in avBNST • Glu projections from the avBNST • avBNST contains the dmBNST and fuBNST • CRF projections from the avBNST • stimulating CRF cells of the mpPVN VI. BNST and endocrine function

  24. dm/fuBNST activity necessary for stimulating activity of PVN (fos) • increased CRF, ACTH and corticosterone from simple stress • avBNST stimulating CRF cells of the mpPVN • Inhibited by NE from LC • binding to a1 + a2 receptors • autoreceptors • NE colocalized with Glu VI. BNST and endocrine function

  25. HPA Axis Stimulation • Indirect • GABA projections from the BNST • amBNST, pBNST, lBNST • vlaBNST, vmaBNST, dmaBNST • Inhibited by GABA from the CeA & MeA • Allows CRF release during acute stress • Produces elevated CRF release during chronic stress conditions VI. BNST and endocrine function

  26. HPA Axis Inhibition • Indirect • GABA projections from the BNST • amBNST, pBNST, lBNST • vlaBNST, vmaBNST, dmaBNST • GABA inhibition is stimulated by Glu • from the Hippocampus (1) especially from ventral subiculum • from the mPFC VI. BNST and endocrine function

  27. Gonadal Axis Inhibition • NE/a1 in BNST inhibits LH release • ↓ frequency and amplitude of LH pulses • E2 is necessary for NE/a1 effect • No effect of a2 or badreno-receptors • NE/a1 in BNST also inhibits CRF • CRF inhibits LH release • NE inhibits LH independently of HPA? VI. BNST and endocrine function

  28. Gonadal Axis Inhibition • Without E2 NE/a1 returns LH pulse frequency to normal • Ovxw/o E2 increase LH pulse frequency • Doubles plasma [LH] • NE/a2 increases pulse amplitude • Electrical stimulation of BNST • Inhibits pre-ovulatory surge of LH • Simulates pre-ovulatory surge of LH VI. BNST and endocrine function

  29. Heart rate • Respiratory depression • BNST simulates increased respiration during stress • Blood Pressure VII. BNST and PHysiology

  30. Anxiety • CRF or UCn1 activity in BNST elicits Anxious behavior • Via CRF1 receptors • In concert with CRF/UCn1/CRF1 in BLA • Reduced social interaction VIII. BNST and Behavior

  31. Anxiety • CRF or UCn1 activity in BNST elicits Anxious behavior • elevated plus maze (EPM) anxiousness • CRF1 in BNST ↓ exploration of open arm • \ increased anxiety • UCn1 in BNST no ↓ exploration of open arm VIII. BNST and Behavior

  32. Anxiety • Long-term, low level CRF activity stimulates anxiety • Subthreshold CRF/UCn1 in BNST yields Anxiety • BNST is not involved in lactate induced anxious behavior • NPY/Y2 are anxiolytic • BNST balances CRF and NPY activity VIII. BNST and Behavior

  33. Stress Behavior • BNST inhibits behavioral despair • BNST lesions increase despair – depression • BNST necessary for unconditioned fear • BNST lesions disrupt fear VIII. BNST and Behavior

  34. BNSTinfluences onlyStress Learning • Necessary for learned helplessness • Stress impedes ability to escape • Necessary for stress enhancement of Fear Conditioning • Not Fear Conditioning itself • Not Spatial Learning VIII. BNST and Behavior

  35. BNSTinfluences onlyStress Learning • Conditioned-Place Selection • CRF1 + CRF2 stimulate conditioned place aversion • Only inhibition of CRF1 stimulates conditioned place preference • Stria terminalis necessary for B/F enhancement of inhibitory avoidance response • Stria terminalis = fibers from CeA to BNST VIII. BNST and Behavior

  36. Reproductive Behavior • BNST • Postpartum • OT into BNST reduces biting • OT into CeA increase biting VIII. BNST and Behavior

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