the integrated bnst
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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
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