Differential effects of oxytocin on mouse hippocampal oscillations in vitro

Abstract

The hypothalamic neuropeptide oxytocin (OT) controls childbirth and lactation, is involved in social behaviors, plays a role in various psychiatric disorders, and has effects on learning and memory. Although behavioral effects of OT have been extensively studied, much less is known about its effects on neuronal and network activity patterns. Here, we investigate the effect of OT on two major patterns of hippocampal network activity in mouse hippocampal slices. We studied different in vitro models of gamma-frequency oscillations and sharp wave-ripple complexes (SPW-R), two patterns implicated in spatial memory formation and memory consolidation respectively. Strikingly, we found a profound difference of OT on these distinct, mutually exclusive activity patterns. While gamma oscillations where not affected by the activation of hippocampal OT receptors, SPW-R were potently and rapidly suppressed. Interestingly, the temporal precision of oscillation-coupled spikes was enhanced at the same time. Thus, OT exerts strongly different modulatory effects on different network patterns, most likely by inhibition of different sets of inhibitory interneurons. The observed dichotomy between gamma and SPW-R oscillations may have profound effects on the behavioral and cognitive effects of OT which are relevant to cognitive processes and to psychiatric diseases.

Oxytocin and vasopressin in the rodent hippocampus

“…Activation of the Oxtr increases evoked population spikes in a kainate‐induced gamma rhythm model in rat slices, resembling enhanced EPSP‐spike coupling but at a network level and under more physiological conditions. However, no other significant effects are seen with Oxtr activation in several different models of in vitro gamma oscillations in either mice or rats . Consistent with other neuromodulators, SPW‐R amplitudes are suppressed with activation of Oxtr in both the CA3 and CA1 regions of mice.…”

“…However, no other significant effects are seen with Oxtr activation in several different models of in vitro gamma oscillations in either mice or rats. 133,154 Consistent with other neuromodulators, 157 SPW-R amplitudes are suppressed with activation of Oxtr in both the CA3 and CA1 regions of mice. Additionally, CA1 SPW-R amplitude is also reduced with application of Avp, however, this effect may be due to Avp interactions with Oxtr.…”

“…At the network level, field recordings with the recording electrode in the stratum radiatum indicate no changes in evoked synaptic input following Oxtr activation, consistent with Oxt‐induced enhancement of EPSP‐spike coupling being dependent on reduced phasic inhibition onto the soma of CA1 pyramidal neurons . However, field recordings with the recording electrode in the CA1 stratum pyramidale show no significant change in evoked population spike amplitude in mice while an increase is observed in rats . The reason for these discrepancies remain unclear but may be due to different recording conditions or species differences that exist between the two studies.…”

“…Consistent with other neuromodulators, SPW‐R amplitudes are suppressed with activation of Oxtr in both the CA3 and CA1 regions of mice. Additionally, CA1 SPW‐R amplitude is also reduced with application of Avp, however, this effect may be due to Avp interactions with Oxtr . As alluded to above, it remains unclear whether both Oxt and Avp modulate overlapping or separate interneuron populations, even though both enhance GABAergic tone in different regions of the hippocampus (see above).…”

“…Additionally, CA1 SPW-R amplitude is also reduced with application of Avp, however, this effect may be due to Avp interactions with Oxtr. 154 As alluded to above, it remains unclear whether both Oxt and Avp modulate overlapping or separate interneuron populations, even though both enhance GABAergic tone in different regions of the hippocampus (see above). Additional studies examining the effects of these peptides on modulating network oscillations and corresponding behavioral states both in vivo and in vitro will be informative toward further understanding the roles of these peptides in hippocampal network function.…”