The Story of BNST Function and Influence

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

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

A. Deep to the Parietal Cortex B. Enclosed by: 1. Lateral ventricle 2. lateral septum 3. Fornix 4. Nucleus accumbens 5. Preoptic area (POA) 6. Hypothalamus

C. Lateral to Anterior Commissure D. Inferior to Lateral Ventricle E. Medial to Internal Capsule 1. And lateral septum F. Fornix G. Nucleus accumbens H. POA I. Superior to hypothalamus

J. In the amygdalar complex K. Medial to BLA (basolateral amygdala) L. Inferior to CeA (central amygdala) M. Superior to MeA (medial amygdala)

Ant Comm

A.Anterior BNST 1.avBNST a.Includes dmBNST b.Includes fuBNST 2.laBNST, maBNST, daBNST B.Boundaries of Anterior BNST?

B. posterior C. lateral 1. dlBNST, vlBNST D. medial 1. amBNST

Anterior Commissure Lateral Ventricle Internal Capsule Dorsal Lateral Anterior Lateral Juxtacapsular Anterior Medial Posterior Lateral Ventral Medial Ventral Lateral Parastrial

A.Major Input from Central Amygdala 1.CeA to vlaBNST – GABA 2.CeA to avBNST - CRF B.MeA to prBNST – GABA C.Other Amygdala?

D.Infralimbic PFC – Glu to dm/fus BNST E.Hippocampus to BNST - Glu 1.vSubiculum – Glu to prBNST F.PFC-Limbic projections onto inhibitory GABA neurons in BNST 1.Counters stimulatory input from amygdala 2.to mpPVN CRF cells

F. LC to avBNST – NE/  2 1.A1 & A2 to avBNST – NE/  2 2.D  H colocalized in BNST with ER  G. VTA to BNST – DA/D 1,2 ? H. dRaphe to aBNST 1. 5-HT/5-HT 1A, 1B,2A,7 ? I. N Sol tract to avBNST – ? J. Cerebellum

A.1 o output from BNST is to PVN 1.GABA from lBNST, aBNST, pBNST to mpPVN (CRF cells) 2.CRF 3.Glu from avBNST to mpPVN

Choi, D. C. et al. J. Neurosci. 2007;27:

B. vlBNST projects to VTA (reward) 1. CRF C. other places?

BNST C. mBNST to N. of the Solitary Tract 1. CRF D. mBNST projects to caudal vl medulla E. mBNST dorsal N of the Vagus (dV) F. Autonomic control 1. Connections from PVN to brainstem too

F. Direct projections to the pons 1. Relay station to relay station a. Stress relay to Cerebellar relay i. Link to cerebellar eye blink circuit

A. HPA Axis Stimulation 1. Direct a. avBNST stimulated by CRF from CeA a. To Glu and CRF cells in avBNST b. Glu projections from the avBNST i. avBNST contains the dmBNST and fuBNST BNST c. CRF projections from the avBNST d. stimulating CRF cells of the mpPVN

d. dm/fuBNST activity necessary for stimulating activity of PVN (fos) i. increased CRF, ACTH and corticosterone from simple stress e. avBNST stimulating CRF cells of the mpPVN i. Inhibited by NE from LC ii. binding to  1 +  2 receptors i. autoreceptors iii. NE colocalized with Glu

A. HPA Axis Stimulation 2. Indirect a. GABA projections from the BNST i. amBNST, pBNST, lBNST ii. vlaBNST, vmaBNST, dmaBNST b. Inhibited by GABA from the CeA & MeA c. Allows CRF release during acute stress d. Produces elevated CRF release during chronic stress conditions

B. HPA Axis Inhibition 1. Indirect a. GABA projections from the BNST i. amBNST, pBNST, lBNST ii. vlaBNST, vmaBNST, dmaBNST b. GABA inhibition is stimulated by Glu i. from the Hippocampus (1) especially from ventral subiculum ii. from the mPFC

C. Gonadal Axis Inhibition 1. NE/  1 in BNST inhibits LH release a. ↓ frequency and amplitude of LH pulses b. E 2 is necessary for NE/  1 effect i. No effect of  2 or  adreno-receptors c. NE/  1 in BNST also inhibits CRF a. CRF inhibits LH release b. NE inhibits LH independently of HPA?

C. Gonadal Axis Inhibition 2. Without E 2 NE/  1 returns LH pulse frequency to normal a. Ovx w / o E 2 increase LH pulse frequency i. Doubles plasma [LH] b. NE/  2 increases pulse amplitude 3. Electrical stimulation of BNST a. Inhibits pre-ovulatory surge of LH b. Simulates pre-ovulatory surge of LH

 Heart rate  Respiratory depression  BNST simulates increased respiration during stress  Blood Pressure

A. Anxiety 1. CRF or UCn 1 activity in BNST elicits Anxious behavior a. Via CRF 1 receptors b. In concert with CRF/UCn 1 /CRF 1 in BLA c. Reduced social interaction

A. Anxiety 1. CRF or UCn 1 activity in BNST elicits Anxious behavior d. elevated plus maze (EPM) anxiousness i. CRF 1 in BNST ↓ exploration of open arm 1)  increased anxiety ii. UCn 1 in BNST no ↓ exploration of open arm

A. Anxiety 2. Long-term, low level CRF activity stimulates anxiety a. Subthreshold CRF/UCn 1 in BNST yields Anxiety 3. BNST is not involved in lactate induced anxious behavior 4. NPY/Y 2 are anxiolytic 5. BNST balances CRF and NPY activity

B. Stress Behavior 1. BNST inhibits behavioral despair a. BNST lesions increase despair – depression 2. BNST necessary for unconditioned fear a. BNST lesions disrupt fear

C. BNST C. BNST influences only Stress Learning 1. Necessary for learned helplessness a. Stress impedes ability to escape 2. Necessary for stress enhancement of Fear Conditioning a. Not Fear Conditioning itself 3. Not Spatial Learning

C. BNST C. BNST influences only Stress Learning 6. Conditioned-Place Selection a. CRF 1 + CRF 2 stimulate conditioned place aversion b. Only inhibition of CRF 1 stimulates conditioned place preference c. Stria terminalis necessary for B/F enhancement of inhibitory avoidance response i. Stria terminalis = fibers from CeA to BNST

D. Reproductive Behavior 1. BNST 2. Postpartum a. OT into BNST reduces biting i. OT into CeA increase biting