Sex-Specific Role for Dopamine Receptor D2 in Dorsal Raphe Serotonergic Neuron Modulation of Defensive Acoustic Startle and Dominance Behavior
| العنوان: | Sex-Specific Role for Dopamine Receptor D2 in Dorsal Raphe Serotonergic Neuron Modulation of Defensive Acoustic Startle and Dominance Behavior |
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| المؤلفون: | Lorna Wu, Krissy A. Lyon, Susan M. Dymecki, Benjamin D. Rood, Rebecca A. Senft, Lisa V. Goodrich |
| المصدر: | eNeuro |
| بيانات النشر: | Society for Neuroscience, 2020. |
| سنة النشر: | 2020 |
| مصطلحات موضوعية: | sex differences, Dorsal Raphe Nucleus, Male, Startle response, Reflex, Startle, Serotonin, Biology, dominance, acoustic startle, Mice, Dorsal raphe nucleus, Dopamine, Dopamine receptor D2, Conditional gene knockout, medicine, dopamine receptor, raphe, Animals, medicine.diagnostic_test, Raphe, General Neuroscience, General Medicine, Acoustics, Cognition and Behavior, Dopamine receptor, Female, Neuroscience, Research Article: New Research, medicine.drug, Serotonergic Neurons |
| الوصف: | Visual Abstract Brain networks underlying states of social and sensory alertness are normally adaptive, influenced by serotonin and dopamine (DA), and abnormal in neuropsychiatric disorders, often with sex-specific manifestations. Underlying circuits, cells, and molecules are just beginning to be delineated. Implicated is a subtype of serotonergic neuron denoted Drd2-Pet1, distinguished by expression of the type-2 DA receptor (Drd2) gene, inhibited cell-autonomously by DRD2 agonism in slice, and, when constitutively silenced in male mice, affects levels of defensive and exploratory behaviors (Niederkofler et al., 2016). Unknown has been whether DRD2 signaling in these Pet1 neurons contributes to their capacity for shaping defensive behaviors. To address this, we generated mice in which Drd2 gene sequences were deleted selectively in Pet1 neurons. We found that Drd2Pet1-CKO males, but not females, demonstrated increased winning against sex-matched controls in a social dominance assay. 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), locomotion, 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) duration, 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. |
| اللغة: | English |
| تدمد: | 2373-2822 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::ee46af403eeb1ddb474c8b11daf17b29 http://europepmc.org/articles/PMC7768286 |
| Rights: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....ee46af403eeb1ddb474c8b11daf17b29 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 23732822 |
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