Neuromodulatory functions exerted by oxytocin on different populations of hippocampal neurons in rodents

Abstract

Oxytocin (OT) is a neuropeptide widely known for its peripheral hormonal effects (i.e., parturition and lactation) and central neuromodulatory functions, related especially to social behavior and social, spatial, and episodic memory. The hippocampus is a key structure for these functions, it is innervated by oxytocinergic fibers, and contains OT receptors (OTRs). The hippocampal OTR distribution is not homogeneous among its subregions and types of neuronal cells, reflecting the specificity of oxytocin’s modulatory action. In this review, we describe the most recent discoveries in OT/OTR signaling in the hippocampus, focusing primarily on the electrophysiological oxytocinergic modulation of the OTR-expressing hippocampal neurons. We then look at the effect this modulation has on the balance of excitation/inhibition and synaptic plasticity in each hippocampal subregion. Additionally, we review OTR downstream signaling, which underlies the OT effects observed in different types of hippocampal neuron. Overall, this review comprehensively summarizes the advancements in unraveling the neuromodulatory functions exerted by OT on specific hippocampal networks.

Oxytocin Modifies the Excitability and the Action Potential Shape of the Hippocampal CA1 GABAergic Interneurons

“…OT is a peptide that can exert multiple modulatory effects through the activation of heterogeneous signaling mechanisms with different final targets and/or by initiating signaling cascades that lead to interconnected and causally related effects [ 14 , 23 ]. An aspect of interest in the evaluation of the modulatory effect of OT on neurons lies in the identification of the relationships that exist between the various parameters altered by the activation of the OTR.…”

“…In the hippocampus, OT plays crucial direct and indirect modulatory roles through highly diverse mechanisms specific to each subregion [ 14 ]. In the CA1, the activation of the OTR is known to increase the firing rate of specific classes of GABAergic INs [ 19 , 20 , 37 ].…”

“…The hippocampus is a key structure for most of these emotional, behavioral, and cognitive functions [ 11 , 12 , 13 ]; therefore, many studies have explored the functional modulation exerted by the OT in this brain area. They have found that the precise action of the OT in the hippocampus is contingent upon a finely tuned, either direct or indirect, modulation of specific neurons within distinct hippocampal subregions [ 14 ]. Specifically, OT exerts its direct effects by binding the oxytocin receptor (OTR) that is selectively expressed by restricted classes of neurons, variable across the hippocampal subregions [ 14 , 15 , 16 , 17 , 18 ].…”

“…They have found that the precise action of the OT in the hippocampus is contingent upon a finely tuned, either direct or indirect, modulation of specific neurons within distinct hippocampal subregions [ 14 ]. Specifically, OT exerts its direct effects by binding the oxytocin receptor (OTR) that is selectively expressed by restricted classes of neurons, variable across the hippocampal subregions [ 14 , 15 , 16 , 17 , 18 ].…”

Oxytocin Enhances Time-Dependent Responses in the Aggressive Zebrafish (Danio rerio)

“…It was proved that OT is capable of reducing amygdala activity by increasing social interactions and reducing anxiety and fear levels in humans [ 44 , 45 ]. In rodent models, OT has been associated with improvements in long-lasting spatial memory, hippocampal synaptic plasticity, and contextual fear memory after administering different hormone doses [ 46 , 47 , 48 ].…”