Biology subjects

Dias, I. C.

Publications and source records attributed to Dias, I. C..

4 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↗

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↗