The Story of BNST Function and Influence

 A. Part of the extended Amygdala

1. Bilaterally B. Relay Station – Bridge

1. from Limbic + PF Corticiesa. Amygdalab. 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 CortexB. Enclosed by:

1. Lateral ventricle

2. lateral septum

3. Fornix

4. Nucleus accumbens

5. Preoptic area (POA)

6. Hypothalamus

C. Lateral to Anterior CommissureD. Inferior to Lateral VentricleE. Medial to Internal Capsule

1. And lateral septumF. FornixG. Nucleus accumbensH. POAI. 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

Ant Comm

A. Anterior BNST1. avBNST

a. Includes dmBNSTb. 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/fusBNST

E. Hippocampus to BNST - Glu

1. vSubiculum – Glu to prBNSTF. PFC-Limbic projections onto

inhibitory GABA neurons in BNST1. Counters stimulatory input

from amygdala

2. to mpPVN CRF cells

F. LC to avBNST – NE/2

1. A1 & A2 to avBNST – NE/2

2. DH colocalized in BNST with ER

G. VTA to BNST – DA/D1,2?

H. dRaphe to aBNST 1. 5-HT/5-HT1A, 1B,2A,7?

I. N Sol tract to avBNST – ?J. Cerebellum

A. 1o 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;27:2025-2034

B. vlBNST projects to VTA

(reward)

1. CRF

C. other places?

C. mBNSTBNST 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 control1.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 Stimulation1. Direct

a. avBNST stimulated by CRF from CeA a. To Glu and CRF cells in avBNST

b. Glu projections from the avBNSTi. avBNST contains the dmBNST and

fuBNST

c. CRF projections from the avBNSTBNST

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 LCii. binding to 1 + 2 receptors

i. autoreceptors

iii.NE colocalized with Glu

A.HPA Axis Stimulation2. Indirect

a. GABA projections from the BNSTi. 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 Inhibition1. Indirect

a. GABA projections from the BNSTi. amBNST, pBNST, lBNST ii. vlaBNST, vmaBNST, dmaBNST

b. GABA inhibition is stimulated by Glui. from the Hippocampus (1) especially from ventral

subiculumii. from the mPFC

C. Gonadal Axis Inhibition1.NE/1 in BNST inhibits LH release

a. ↓ frequency and amplitude of LH pulsesb. E2 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 Inhibition2. Without E2 NE/1 returns LH pulse

frequency to normala. Ovx w/o E2 increase LH pulse

frequency

i. Doubles plasma [LH]b. NE/2 increases pulse amplitude

3. Electrical stimulation of BNSTa. Inhibits pre-ovulatory surge of LHb. Simulates pre-ovulatory surge of LH

Heart rate Respiratory depression BNST simulates increased

respiration during stress Blood Pressure

A.Anxiety1.CRF or UCn1 activity in BNST

elicits Anxious behaviora. Via CRF1 receptors

b. In concert with CRF/UCn1/CRF1 in BLA

c. Reduced social interaction

A.Anxiety1.CRF or UCn1 activity in BNST

elicits Anxious behaviord. elevated plus maze (EPM)

anxiousnessi. CRF1 in BNST ↓ exploration of open

arm1) increased anxiety

ii. UCn1 in BNST no ↓ exploration of open arm

A.Anxiety2. Long-term, low level CRF activity

stimulates anxietya. Subthreshold CRF/UCn1 in BNST

yields Anxiety

3. BNST is not involved in lactate induced anxious behavior

4. NPY/Y2 are anxiolytic

5. BNST balances CRF and NPY activity

B. Stress Behavior1. BNST inhibits behavioral despair

a. BNST lesions increase despair – depression

2. BNST necessary for unconditioned fear

a. BNST lesions disrupt fear

C.C. BNSTBNST influences only Stress Learning

1.Necessary for learned helplessnessa. Stress impedes ability to escape

2.Necessary for stress enhancement of Fear Conditioninga. Not Fear Conditioning itself

3.Not Spatial Learning

C.C. BNSTBNST influences only Stress Learning6. Conditioned-Place Selection

a. CRF1 + CRF2 stimulate conditioned place aversion

b. Only inhibition of CRF1 stimulates conditioned place preference

c. Stria terminalis necessary for B/F enhancement of inhibitory avoidance responsei. Stria terminalis = fibers from CeA to

BNST

D. Reproductive Behavior1. BNST2. Postpartum

a. OT into BNST reduces bitingi. OT into CeA increase biting