Social Recognition is a fundamental skill that forms the basis of behaviors essential to the proper functioning of pair or group living in most social species. We review here various neurobiological and genetic studies that point to an interplay of oxytocin (OT), arginine-vasopressin (AVP), and the gonadal hormones, estrogens and testosterone, in the mediation of social recognition. Results of a number of studies have shown that OT and its actions at the medial amygdala seem to be essential for social recognition in both sexes. Estrogens facilitate social recognition, possibly by regulating OT production in the hypothalamus and the OT receptors at the medial amygdala. Estrogens also affect social recognition on a rapid time scale, likely through nongenomic actions. The mechanisms of these rapid effects are currently unknown but available evidence points at the hippocampus as the possible site of action. Male rodents seem to be more dependent on AVP acting at the level of the lateral septum for social recognition than female rodents. Results of various studies suggest that testosterone and its metabolites (including estradiol) influence social recognition in males primarily through the AVP V1a receptor. Overall, it appears that gonadal hormone modulation of OT and AVP regulates and fine tunes social recognition and those behaviors that depend upon it (e.g., social bonds, social hierarchies) in a sex specific manner. This points at an important role for these neuroendocrine systems in the regulation of the sex differences that are evident in social behavior and of sociality as a whole.

Estrogen receptor (ER) agonists rapidly affect neural plasticity within 1 h, suggesting they play a functional role in learning and memory. However, behavioral learning experiments on such a rapid time scale are lacking. Therefore we investigated whether the ERα agonist propyl pyrazole triol (PPT) and ERβ agonist diarylpropionitrile (DPN) could affect social recognition, object recognition, or object placement learning within 40 min of drug administration. At the same time, we examined their effects on CA1 hippocampal dendritic spines. Ovariectomized female CD1 mice were administered a range of PPT or DPN doses (0, 30, 50, 75, or 150 μg/mouse). PPT at the middle doses improved social recognition, facilitated object recognition and placement at a dose of 75 μg, and increased dendritic spine density in the stratum radiatum and lacunosum-moleculare. In contrast, DPN impaired social recognition at higher doses, did not affect object recognition, but slightly facilitated object placement learning at the 75-μg dose. DPN did not affect spines in the stratum radiatum but decreased spine density and increased spine length in the lacunosum-moleculare. This suggests that rapid estrogen-mediated learning enhancements may predominantly be mediated through ERα, while the effects of DPN are weaker and may depend on the learning paradigm. The role of ERα and ERβ in learning and memory may vary depending on the timing of drug administration, as genomic studies often implicate ERβ in enhancing effects on learning and memory. To our knowledge, this is the first report of estrogens' effects on learning within such a short time frame.

Current thought envisions dopamine neurons conveying the reinforcing effect of the unconditioned stimulus during associative learning to the axons of Drosophila mushroom body Kenyon cells for normal olfactory learning. Here, we show using functional GFP reconstitution experiments that Kenyon cells and dopamine neurons from axoaxonic reciprocal synapses. The dopamine neurons receive cholinergic input via nicotinic acetylcholine receptors from the Kenyon cells; knocking down these receptors impairs olfactory learning revealing the importance of these receptors at the synapse. Blocking the synaptic output of Kenyon cells during olfactory conditioning reduces presynaptic calcium transients in dopamine neurons, a finding consistent with reciprocal communication. Moreover, silencing Kenyon cells decreases the normal chronic activity of the dopamine neurons. Our results reveal a new and critical role for positive feedback onto dopamine neurons through reciprocal connections with Kenyon cells for normal olfactory learning.

Significance: Estrogens are known to rapidly affect learning and memory, but how they do so is not well understood. Here we identify the hippocampus as a brain structure responsible for rapid estradiol-induced improvement of general discrimination learning in female mice, which coincides with a substantial increase in hippocampal dendritic spines, the postsynaptic sites of excitatory synapses. Until now, it had been assumed that estradiol-induced increases in hippocampal synapses would result in increased excitatory input into the neuron. Surprisingly, we find the opposite: increases in hippocampal spines are associated with a decrease in the excitatory glutamatergic input. This finding suggests that estradiol improves learning through inducing the formation of silent or immature synapses, which provide the substrate for storing new memories.