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VMHvll^Cckar cells dynamically control female sexual behaviors over the reproductive cycle.

ABSTRACT: Sexual behavior is fundamental for the survival of mammalian species and thus supported by dedicated neural substrates. The ventrolateral part of ventromedial hypothalamus (VMHvl) is an essential locus for controlling female sexual behaviors, but recent studies revealed the molecular complexity and functional heterogeneity of VMHvl cells. Here, we identify the cholecystokinin A receptor (Cckar)-expressing cells in the lateral VMHvl (VMHvll^Cckar) as the key controllers of female sexual behaviors. The inactivation of VMHvll^Cckar cells in female mice diminishes their interest in males and sexual receptivity, whereas activating these cells has the opposite effects. Female sexual behaviors vary drastically over the reproductive cycle. In vivo recordings reveal reproductive-state-dependent changes in VMHvll^Cckar cell spontaneous activity and responsivity, with the highest activity occurring during estrus. These in vivo response changes coincide with robust alternation in VMHvll^Cckar cell excitability and synaptic inputs. Altogether, VMHvll^Cckar cells represent a key neural population dynamically controlling female sexual behaviors over the reproductive cycle.

SUBMITTER: Yin L

PROVIDER: S-EPMC9509472 | biostudies-literature | 2022 Sep

REPOSITORIES: biostudies-literature

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VMHvll<sup>Cckar</sup> cells dynamically control female sexual behaviors over the reproductive cycle.

Yin Luping L Hashikawa Koichi K Hashikawa Yoshiko Y Osakada Takuya T Lischinsky Julieta E JE Diaz Veronica V Lin Dayu D

Neuron 20220726 18

Sexual behavior is fundamental for the survival of mammalian species and thus supported by dedicated neural substrates. The ventrolateral part of ventromedial hypothalamus (VMHvl) is an essential locus for controlling female sexual behaviors, but recent studies revealed the molecular complexity and functional heterogeneity of VMHvl cells. Here, we identify the cholecystokinin A receptor (Cckar)-expressing cells in the lateral VMHvl (VMHvll<sup>Cckar</sup>) as the key controllers of female sexual ...[more]

PMID: 35896109

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Project description:Despite the advent of combination anti-retroviral therapy (cART), nearly half of people infected with HIV treated with cART still exhibit HIV-associated neurocognitive disorders (HAND). HAND can be worsened by co-morbid opioid use disorder. The basal ganglia are particularly vulnerable to HIV-1 and exhibit higher viral loads and more severe pathology, which can be exacerbated by co-exposure to opioids. Evidence suggests that dopaminergic neurotransmission is disrupted by HIV exposure, however, little is known about whether co-exposure to opioids may alter neurotransmitter levels in the striatum and if this in turn influences behavior. Therefore, we assayed motor, anxiety-like, novelty-seeking, exploratory, and social behaviors, and levels of monoamines and their metabolites following 2 weeks and 2 months of Tat and/or morphine exposure in transgenic mice. Morphine decreased dopamine levels, but significantly elevated norepinephrine, the dopamine metabolites dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA), and the serotonin metabolite 5-hydroxyindoleacetic acid, which typically correlated with increased locomotor behavior. The combination of Tat and morphine altered dopamine, DOPAC, and HVA concentrations differently depending on the neurotransmitter/metabolite and duration of exposure but did not affect the numbers of tyrosine hydroxylase-positive neurons in the mesencephalon. Tat exposure increased the latency to interact with novel conspecifics, but not other novel objects, suggesting the viral protein inhibits exploratory behavior initiation in a context-dependent manner. By contrast, and consistent with prior findings that opioid misuse can increase novelty-seeking behavior, morphine exposure increased the time spent exploring a novel environment. Finally, Tat and morphine interacted to affect locomotor activity in a time-dependent manner, while grip strength and rotarod performance were unaffected. Together, our results provide novel insight into the unique effects of HIV-1 Tat and morphine on monoamine neurochemistry that may underlie their divergent effects on motor and exploratory behavior.

Dataset Information

VMHvll^Cckar cells dynamically control female sexual behaviors over the reproductive cycle.

Publications

VMHvll<sup>Cckar</sup> cells dynamically control female sexual behaviors over the reproductive cycle.

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Dataset Information

VMHvllCckar cells dynamically control female sexual behaviors over the reproductive cycle.

Publications

VMHvll<sup>Cckar</sup> cells dynamically control female sexual behaviors over the reproductive cycle.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets

VMHvll^Cckar cells dynamically control female sexual behaviors over the reproductive cycle.