Biology subjects

Lima, S. Q.

Publications and source records attributed to Lima, S. Q..

8 recordsLinked to original sources

bioRxiv2026

Distinct afferent signatures onto anterior and posterior VMHvl subdomains and their progesterone receptor-expressing neurons

Female sexual behavior is fundamentally coupled to reproductive state, requiring the dynamic and coordinated regulation of sexual receptivity and rejection across the estrous cycle. In mice, these opposing behaviors are controlled by distinct neuronal subpopulations within the anteroposterior subdomains of the ventrolateral ventromedial hypothalamus (VMHvl): the posterior VMHvl (pVMHvl) promotes sexual receptivity, whereas the anterior VMHvl (aVMHvl) drives sexual rejection. Although progesterone receptor-expressing (PR) neurons in both subregions are essential for these behaviors, the circuit mechanisms underlying this anteroposterior functional segregation remain poorly understood. Here, we investigated whether anterior and posterior VMHvl subdomains receive distinct afferent inputs that could support their divergent roles, and whether these inputs specifically target PR neurons. By combining retrograde tracing with whole-brain, machine learning-assisted quantification, we first mapped the afferent connectivity of the aVMHvl and pVMHvl. We found that while the two subdomains share the majority of their inputs, they also receive distinct and biased projections. The aVMHvl preferentially receives inputs from the anterior hypothalamic nucleus, paraventricular and peripeduncular thalamic nuclei, and the parabrachial nucleus, while the pVMHvl is preferentially innervated by the preoptic area, dorsal and ventral premammillary nuclei and anteroventral periventricular nucleus. To determine whether the identified afferents directly synapse onto the PR neurons, we performed monosynaptic rabies tracing from anterior and posterior VMHvl PR neurons. These experiments revealed that most anterior- and posterior-biased projections directly targeted PR VMHvl neurons. In addition, projections from the paraventricular thalamus, periaqueductal gray, and several pontine nuclei preferentially innervated aVMHvlPR neurons, whereas inputs from the mammillary nuclei mostly targeted pVMHvlPR neurons. Together, our results reveal distinct afferent architectures onto anterior and posterior PR VMHvl neurons, providing a circuit-level framework for understanding how hormonal state flexibly biases female sexual behavior toward receptivity or rejection.

neuroscience↗

bioRxiv2026

Neural substrates of female sexual rejection: hypothalamic pathways to the periaqueductal gray

Selecting an appropriate behavioral response according to ones internal state is essential for well-being. Across the reproductive cycle, fluctuating levels of sex hormones align female behavior with reproductive capacity by modulating neuronal circuits that express hormone receptors. Sex hormone receptor-expressing neurons present along the anterior-posterior axis of the ventrolateral region of the ventromedial hypothalamus (VMHvl) are key regulators of female sexual behavior. While posterior progesterone receptor-expressing neurons of the VMHvl (pVMHvlPR+) are fundamental for female sexual receptivity during the receptive phase of the reproductive cycle, we have recently shown that anterior VMHvlPR+ (aVMHvlPR+) neurons are involved in rejection behavior when non-receptive. Here, we mapped the connectional architecture of aVMHvlPR+ neurons using viral tracing approaches. As expected, these neurons strongly project to several hypothalamic areas. Furthermore, consistent with previous reports, we show that aVMHvlPR+ neurons robustly project to several columns of the periaqueductal gray (PAG) along its anterior-posterior axis. Artificial activation of aVMHvlPR+ somas selectively recruits the dorsomedial PAG (dmPAG). Optogenetic activation of aVMHvlPR+ axons in the dmPAG partially recapitulates the rejection phenotype observed upon activation of aVMHvlPR+ somas, increasing the rate of rejections in receptive females. These findings reveal a putative pathway regulating female rejection behavior within a more complex circuit, ensuring that mating does not occur during non fertile periods.

neuroscience↗

bioRxiv2023

Cyclical control of female rejection behavior by progesterone receptor expressing neurons of the anterior ventromedial hypothalamus

Internal state-dependent behavioral responses, such as the switch between rejection and acceptance of sexual advances depending on a females reproductive capacity, are fundamental to maintain social interactions and wellbeing. Here we characterize a dedicated circuit for the cyclical control of rejection behavior in the mouse, located in the anterior ventrolateral ventromedial hypothalamus (aVMHvl). In vivo recordings reveal that progesterone receptor expressing neurons of the aVMHvl (aVMHvlPr+) are active during rejection but silent when females accept the male. Moreover, we show that aVMHvlPr+ neurons receive reduced excitatory to inhibitory synaptic input balance during the receptive phase of the reproductive cycle. Finally, optogenetic activation of aVMHvlPr+ neurons in receptive females is sufficient to increase rejection behavior, disrupting the probability of copulation, without affecting other male-directed interactions. This population of aVMHvlPr+ neurons is thus a key neural substrate controlling female sexual behavior, providing an additional barrier to mating when fertilization is not possible.

neuroscience↗

bioRxiv2022

A galanin-positive population of lumbar spinal cord neurons modulates sexual behavior and arousal

During sex, male arousal increases to the ejaculatory threshold, allowing genital sensory input to trigger ejaculation. While copulation and sexual arousal are thought to be centrally regulated by the brain, ejaculation is considered a reflex controlled by a spinal circuit. In this framework, the spinal cord is assumed to be strongly inhibited by descending input from the brain until the ejaculatory threshold, playing no role in the regulation of copulatory behavior. However, this remains untested. Here, we mapped the spinal circuit controlling the bulbospongiosus muscle, which is involved in sperm expulsion in mice. Our findings reveal that bulbospongiosus muscle-motor neurons receive input from galanin-expressing interneurons. This galanin-positive population receives genital input and, while its stimulation leads to bulbospongiosus muscle activity, the evoked muscle-potentials are dependent on spinalization, the males internal state and decrease with repeated stimulation. Moreover, ablation of galanin neurons affected the latency to ejaculate and altered the copulatory pattern. These results suggest an unexpected role of spinal circuits in the control of copulation and arousal, in addition to its established role in ejaculation.

neuroscience↗

bioRxiv2021

The structural and electrophysiological properties of progesterone receptor expressing neurons vary along the anterior-posterior axis of the ventromedial hypothalamus and undergo local changes across the reproductive cycle

Sex hormone levels continuously fluctuate across the reproductive cycle, changing the activity of neuronal circuits to coordinate female behavior and reproductive capacity. The ventrolateral division of the ventromedial hypothalamus (VMHvl) contains neurons expressing receptors for sex hormones and its function is intimately linked to female sexual receptivity. However, recent findings suggest that the VMHvl is functionally heterogeneous. Here, we used whole cell recordings and intracellular labeling to characterize the electrophysiological and morphological properties of individual VMHvl neurons in naturally cycling females. We found that the properties of progesterone receptor expressing (PR+) neurons, but not PR- neurons, depended systematically on the neurons location along the anterior-posterior axis of the VMHvl and the phase within the reproductive cycle. Prominent amongst this, the resting membrane potential of anterior PR+ neurons decreased during the receptive phase, while the excitability of medial PR+ neurons increased during the non-receptive phase. During the receptive phase of the cycle, posterior PR+ neurons simultaneously showed an increase in dendritic complexity and a decrease in spine density. These findings reveal an extensive diversity of local rules driving structural and physiological changes in response to fluctuating levels of sex hormones, supporting the anatomical and functional subdivision of the VMHvl and its possible role in the orchestration of different aspects of female socio-sexual behavior.

neuroscience↗

bioRxiv2020

No evidence for prolactin's involvement in the post-ejaculatory refractory period

In many species, ejaculation is followed by a state of decreased sexual motivation, the post-ejaculatory refractory period. Several lines of evidence have suggested prolactin, a pituitary hormone released around the time of ejaculation in humans and other animals, to be a decisive player in the establishment of the refractory period. However, data supporting this hypothesis is controversial. We took advantage of two different strains of house mouse, a wild derived and a classical laboratory strain, that differ substantially in their sexual behavior, to investigate prolactins involvement in sexual motivation and the refractory period. First, we show that there is prolactin release during sexual behavior in male mice. Second, using a pharmacological approach, we show that acute manipulations of prolactin levels, either mimicking the natural release during sexual behavior or inhibiting its occurrence, do not affect sexual motivation or shorten the refractory period, respectively. Therefore, we show compelling evidence refuting the idea that prolactin released during copulation is involved in the establishment of the refractory period, a long-standing hypothesis in the field of behavioral endocrinology.

animal behavior and cognition↗

bioRxiv2019

Sexual imprinting overrides order effects

Mate choice is a complex decision that requires the integration of cues from potential mates with individual preferences. Choosers preferences are shaped by recent events, early life experience and by the evolutionary history of its own species. To better understand the interaction between these factors, we studied mate choice in the female house mouse, Mus musculus. Females of one of the musculus subspecies, Mus musculus musculus, show preference for males of their own subspecies compared to males of the sibling subspecies, Mus musculus domesticus. Such an assortative preference is ecologically relevant at contact zones, where it contributes to the reproductive isolation of sympatric populations and can be reproduced in controlled laboratory conditions, but its origins are still under debate. Here, we show that female mouse mate choice depends on both early postnatal life experience and the order of prospective mates encountered as an adult and that these effects interact asymmetrically. Whereas females raised in their normal M. m. musculus environment display a robust assortative preference, females fostered in a M. m. domesticus family prefer the first male encountered, regardless of subspecies. Thus, early life experience of M. m. musculus females, when concordant with genetic self-identity, overrides sampling order effects, ensuring robust assortative choice. In the absence of this match between phylogeny and early life experience, first impression effects dominate mate choice.

animal behavior and cognition↗

bioRxiv2018

Differential encoding of predator fear in the ventromedial hypothalamus and periaqueductal grey

The ventromedial hypothalamus is a central node of the mammalian predator defense network. Stimulation of this structure in rodents and primates elicits abrupt defensive responses, including flight, freezing, sympathetic activation, and panic, while inhibition reduces defensive responses to predators. The major efferent target of the ventromedial hypothalamus is the dorsal periaqueductal grey, and stimulation of this structure also elicits flight, freezing, and sympathetic activation. However, reversible inhibition experiments suggest that the ventromedial hypothalamus and periaqueductal grey play distinct roles in the control of defensive behavior, with the former proposed to encode an internal state necessary for the motivation of defensive responses, while the latter serves as a motor pattern initiator. Here we used electrophysiological recordings of single units in behaving mice exposed to a rat to investigate the encoding of predator fear in the dorsomedial division of the ventromedial hypothalamus and the dorsal periaqueductal grey. Distinct correlates of threat intensity and motor responses were found in both structures, suggesting a distributed encoding of sensory and motor features in the medial hypothalamic-brainstem instinctive network.

neuroscience↗