Transcript Cliff - USD Biology

The Story of BNST Function and Influence
THE INTEGRATED BNST
I. WHAT IS THE BNST
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
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
II. WHERE IS THE BNST
A. Deep to the Parietal Cortex
B. Enclosed by:
1.
2.
3.
4.
5.
6.
Lateral ventricle
lateral septum
Fornix
Nucleus accumbens
Preoptic area (POA)
Hypothalamus
II. WHERE IS THE BNST
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
II. WHERE IS THE BNST
J. In the amygdalar complex
K. Medial to BLA (basolateral amygdala)
L. Inferior to CeA (central amygdala)
M. Superior to MeA (medial amygdala)
II. WHERE IS THE BNST
II. WHERE IS THE BNST
II. WHERE IS THE BNST
Ant Comm
II. WHERE IS THE BNST
Ant Comm
II. WHERE IS THE BNST
III. SUBDIVISIONS OF THE BNST
A. Anterior BNST
1. avBNST
a.
b.
Includes dmBNST
Includes fuBNST
2. laBNST, maBNST, daBNST
B. Boundaries of Anterior BNST?
III. SUBDIVISONS OF THE BNST
B. posterior
C. lateral
1. dlBNST, vlBNST
D. medial
1. amBNST
III. SUBDIVISIONS OF THE BNST
Lateral Ventricle
Internal Capsule
Dorsal Lateral
Anterior Lateral
Juxtacapsular
Anterior Medial
Anterior Commissure
Posterior Lateral
Ventral Medial
Ventral Lateral
Parastrial
IV. INPUTS TO BNST
A. Major Input from Central Amygdala
1. CeA to vlaBNST – GABA
2. CeA to avBNST - CRF
B. MeA to prBNST – GABA
C. Other Amygdala?
IV. INPUTS TO BNST
D. Infralimbic PFC – Glu to dm/fusBNST
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
IV. INPUTS TO BNST – Brainstem Regions
F. LC to avBNST – NE/a2
1.
2.
A1 & A2 to avBNST – NE/a2
DbH colocalized in BNST with ERa
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
V. PROJECTIONS FROM BNST
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
IV-V. INPUTS TO/PROJECTIONS FROM BNST
Choi, D. C. et al. J. Neurosci. 2007;27:2025-2034
V. PROJECTIONS FROM THE BNST - Brainstem
B. vlBNST projects to VTA (reward)
1. CRF
C. other places?
V. PROJECTIONS FROM THE BNST - Brainstem
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
V. PROJECTIONS FROM THE BNST - Brainstem
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
VI. BNST AND ENDOCRINE FUNCTION
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
c. CRF projections from the avBNST
d. stimulating CRF cells of the mpPVN
VI. BNST AND ENDOCRINE FUNCTION
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 a1 + a2 receptors
i. autoreceptors
iii. NE colocalized with Glu
VI. BNST AND ENDOCRINE FUNCTION
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
VI. BNST AND ENDOCRINE FUNCTION
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
VI. BNST AND ENDOCRINE FUNCTION
C. Gonadal Axis Inhibition
1. NE/a1 in BNST inhibits LH release
a. ↓ frequency and amplitude of LH pulses
b. E2 is necessary for NE/a1 effect
i. No effect of a2 or b adreno-receptors
c. NE/a1 in BNST also inhibits CRF
a. CRF inhibits LH release
b. NE inhibits LH independently of HPA?
VI. BNST AND ENDOCRINE FUNCTION
C. Gonadal Axis Inhibition
2. Without E2 NE/a1 returns LH pulse
frequency to normal
a. Ovx w/o E2 increase LH pulse frequency
i. Doubles plasma [LH]
b. NE/a2 increases pulse amplitude
3. Electrical stimulation of BNST
a. Inhibits pre-ovulatory surge of LH
b. Simulates pre-ovulatory surge of LH
VII. BNST AND PHYSIOLOGY
Heart rate
 Respiratory depression

 BNST
simulates increased respiration
during stress

Blood Pressure
VIII. BNST AND BEHAVIOR
A. Anxiety
1. CRF or UCn1 activity in BNST elicits
Anxious behavior
a. Via CRF1 receptors
b. In concert with CRF/UCn1/CRF1 in BLA
c. Reduced social interaction
VIII. BNST AND BEHAVIOR
A. Anxiety
1. CRF or UCn1 activity in BNST elicits
Anxious behavior
d. elevated plus maze (EPM) anxiousness
i. CRF1 in BNST ↓ exploration of open arm
1) \ increased anxiety
ii. UCn1 in BNST no ↓ exploration of open arm
VIII. BNST AND BEHAVIOR
A. Anxiety
2. Long-term, low level CRF activity
stimulates anxiety
a. 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
VIII. BNST AND BEHAVIOR
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
VIII. BNST AND BEHAVIOR
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
VIII. BNST AND BEHAVIOR
C. BNST influences only Stress Learning
6. 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
response
i. Stria terminalis = fibers from CeA to BNST
VIII. BNST AND BEHAVIOR
D. Reproductive Behavior
1. BNST
2. Postpartum
a. OT into BNST reduces biting
i. OT into CeA increase biting