The paraventricular thalamus provides a polysynaptic brake on limbic CRF neurons to sex-dependently blunt binge alcohol drinking and avoidance behavior in mice
Bed nucleus of the stria terminalis (BNST) neurons that synthesize corticotropin-releasing factor (CRF) drive binge alcohol drinking and anxiety. Here, we found that female C57BL/6J mice binge drink more than males and have greater basal BNST CRF neuron excitability and synaptic excitation. We ident...
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Veröffentlicht in: | Nature communications 2021-08, Vol.12 (1), p.5080-5080, Article 5080 |
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Sprache: | eng |
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Zusammenfassung: | Bed nucleus of the stria terminalis (BNST) neurons that synthesize corticotropin-releasing factor (CRF) drive binge alcohol drinking and anxiety. Here, we found that female C57BL/6J mice binge drink more than males and have greater basal BNST
CRF
neuron excitability and synaptic excitation. We identified a dense VGLUT2 + synaptic input from the paraventricular thalamus (PVT) that releases glutamate directly onto BNST
CRF
neurons but also engages a large BNST interneuron population to ultimately inhibit BNST
CRF
neurons, and this polysynaptic PVT
VGLUT2
-BNST
CRF
circuit is more robust in females than males. Chemogenetic inhibition of the PVT
BNST
projection promoted binge alcohol drinking only in female mice, while activation reduced avoidance behavior in both sexes. Lastly, repeated binge drinking produced a female-like phenotype in the male PVT-BNST
CRF
excitatory synapse without altering the function of PVT
BNST
neurons per se. Our data describe a complex, feedforward inhibitory PVT
VGLUT2
-BNST
CRF
circuit that is sex-dependent in its function, behavioral roles, and alcohol-induced plasticity.
Bed nucleus of the stria terminalis (BNST) neurons that synthesize and release the stress neuropeptide corticotropin-releasing factor drive binge alcohol drinking and anxiety. The authors describe a complex feedforward inhibitory PVT
VGLUT2
-BNST
CRF
circuit in mice that plays sex-dependent roles in alcohol drinking and avoidance behavior. |
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ISSN: | 2041-1723 2041-1723 |
DOI: | 10.1038/s41467-021-25368-y |