TY - JOUR
T1 - Sex-specific role for dopamine receptor d2 in dorsal raphe serotonergic neuron modulation of defensive acoustic startle and dominance behavior
AU - Lyon, Krissy A.
AU - Rood, Benjamin D.
AU - Wu, Lorna
AU - Senft, Rebecca A.
AU - Goodrich, Lisa V.
AU - Dymecki, Susan M.
N1 - Funding Information:
This work was supported by the National Institutes of Health National Institute on Drug Abuse Grant R01 DA034022 (to S.M.D.) and Blueprint Award NS108515 (to K.A.L.), the National Institute on Deafness and Other Communication Grant R01 DC015974 (to L.V.G.), and G.V.R. Khodadad Fund for studies of EPS (S.M. D.). K.A.L. was a Howard Hughes Medical Institute Gilliam Fellow.
Publisher Copyright:
© 2020 Lyon et al.
PY - 2020/11/1
Y1 - 2020/11/1
N2 - Drd2Pet1-CKO females, but not males, exhibited blunting of the acoustic startle response, a protective, defensive reflex. Indistinguishable from controls were auditory brainstem responses (ABRs), loco-motion, cognition, and anxiety-like and depression-like behaviors. Analyzing wild-type Drd2-Pet1 neurons, we found sex-specific differences in the proportional distribution of axonal collaterals, in action potential (AP) du-ration, and in transcript levels of Gad2, important for GABA synthesis. Drd2Pet1-CKO cells displayed sex-specific differences in the percentage of cells harboring Gad2 transcripts. Our results suggest that DRD2 function in Drd2-Pet1 neurons is required for normal defensive/protective behaviors in a sex-specific manner, which may be influenced by the identified sex-specific molecular and cellular features. Related behaviors in humans too show sex differences, suggesting translational relevance.
AB - Drd2Pet1-CKO females, but not males, exhibited blunting of the acoustic startle response, a protective, defensive reflex. Indistinguishable from controls were auditory brainstem responses (ABRs), loco-motion, cognition, and anxiety-like and depression-like behaviors. Analyzing wild-type Drd2-Pet1 neurons, we found sex-specific differences in the proportional distribution of axonal collaterals, in action potential (AP) du-ration, and in transcript levels of Gad2, important for GABA synthesis. Drd2Pet1-CKO cells displayed sex-specific differences in the percentage of cells harboring Gad2 transcripts. Our results suggest that DRD2 function in Drd2-Pet1 neurons is required for normal defensive/protective behaviors in a sex-specific manner, which may be influenced by the identified sex-specific molecular and cellular features. Related behaviors in humans too show sex differences, suggesting translational relevance.
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U2 - 10.1523/ENEURO.0202-20.2020
DO - 10.1523/ENEURO.0202-20.2020
M3 - Article
C2 - 33214315
AN - SCOPUS:85099073481
SN - 2373-2822
VL - 7
SP - 1
EP - 23
JO - eNeuro
JF - eNeuro
IS - 6
M1 - ENEURO.0202-20.2020
ER -