Accumulating evidence has revealed the existence of functional astrocyte-neuron communication based on the ability of astrocytes to respond to neurotransmitters and release gliotransmitters. However, little is known about how other signaling molecules, such as hormones, impact astrocyte function. Estradiol (E2) is an important hormone known to regulate neuronal activity, synaptic transmission, plasticity, and animal behavior. However, whether E2 specifically signals to astrocytes in situ and the functional consequences on astrocyte-neuron communication remain unknown. Therefore, we investigated the impact of estradiol on astrocyte activity and astrocyte-neuron communication in the mouse hippocampus. Using an RNAscope approach, we determined that estrogen receptors (ERα and ERβ) are expressed in astrocytes in both female and male mice. In both sexes, confocal imaging of hippocampal slices determined that astrocytes respond to locally applied E2 with calcium elevations. In pyramidal neurons, slow inward currents (SICs) are mediated by the activation of extrasynaptic NMDA receptors and indicate gliotransmission. Electrophysiological recordings of hippocampal neurons determined that E2 increases the frequency, but not the amplitude, of SICs. We also recorded excitatory synaptic transmission evoked by Schaffer collateral stimulation. Here, only in females, did E2 produce a reduction in excitatory synaptic transmission. The E2-induced effects on the astrocyte calcium signal and gliotransmission were prevented by the broad estrogen receptor antagonist ICI 182,780. Taken together, these results demonstrate the existence of estradiol-mediated astrocyte-neuron communication in both female and male mice. They reveal that E2 can signal to astrocytes and, through this signaling, E2 may regulate neuronal activity and synaptic transmission.

Like many social behaviors, aggression can be rewarding, leading to behavioral plasticity. One outcome of reward-induced aggression is the long-term increase in the speed in which future aggression-based encounters is initiated. This form of aggression impacts dendritic structure and excitatory synaptic neurotransmission in the nucleus accumbens, a brain region well known to regulate motivated behaviors. Yet, little is known about the intracellular signaling mechanisms that drive these structural/functional changes and long-term changes in aggressive behavior. This study set out to further elucidate the intracellular signaling mechanisms regulating the plasticity in neurophysiology and behavior that underlie the rewarding consequences of aggressive interactions. Female Syrian hamsters experienced zero, two or five aggressive interactions and the phosphorylation of proteins in reward-associated regions was analyzed. We report that aggressive interactions result in a transient increase in the phosphorylation of extracellular-signal related kinase 1/2 (ERK1/2) in the nucleus accumbens. We also report that aggressive interactions result in a transient decrease in the phosphorylation of mammalian target of rapamycin (mTOR) in the medial prefrontal cortex, a major input structure to the nucleus accumbens. Thus, this study identifies ERK1/2 and mTOR as potential signaling pathways for regulating the long-term rewarding consequences of aggressive interactions. Furthermore, the recruitment profile of the ERK1/2 and the mTOR pathways are distinct in different brain regions.

Melanocortin 3 receptors (MC3R) and melanocortin 4 receptors (MC4R) are vital in regulating a variety of functions across many species. For example, the dysregulation of these receptors results in obesity and dysfunction in sexual behaviors. Only a handful of studies have mapped the expression of MC3R and MC4R mRNA across the central nervous system, with the primary focus on mice and rats. Because Syrian hamsters are valuable models for functions regulated by melanocortin receptors, our current study maps the distribution of MC3R and MC4R mRNA in the Syrian hamster telencephalon, diencephalon, and midbrain using RNAscope. We found that the expression of MC3R mRNA was lowest in the telencephalon and greatest in the diencephalon, whereas the expression of MC4R mRNA was greatest in the midbrain. A comparison of these findings to previous studies found that MC3R and MC4R expression is similar in some brain regions across species and divergent in others. In addition, our study identifies novel brain regions for the expression of MC3Rs and MC4Rs, and identifies cells that co-express bothMC3 and MC4 receptors within certain brain regions.

Kisspeptin (Kiss1) and kisspeptin 1 receptor (Kiss1R) are vital in regulating various functions across many species, primarily those relating to reproduction. The kisspeptin system has recently attracted clinical interest as a potential therapeutic treatment for patients with hypoactive sexual desire disorder. This study maps the distribution of Kiss1 and Kiss1R mRNA in the Syrian hamster forebrain using dual-labeled RNAscope. In our study, the distributions of kisspeptin and its receptor were mapped across adult males and females on day 1 or day 2 of their estrous cycle. Conditioned place preference was used to observe the potential effect of kisspeptin on sexual reward in female hamsters. The expression of kisspeptin was greater in females than males, with the estrous cycle having no effect on expression. A comparison of these findings to those in other species revealed that the expression in Syrian hamsters was similar to that reported for other species, demonstrating the conservation of expression. Kisspeptin did not influence sexual reward in females, nor did it affect measures of their primary sexual behavior. These findings provide additional insights into the expression and function of kisspeptin across novel species and add to ongoing research in understanding how kisspeptin may influence sexual desire in animals, including humans.