Degree

Doctor of Philosophy (PhD)

Department

Department of Biological sciences

Document Type

Dissertation

Abstract

Oxytocin drives milk ejection during lactation by inducing contraction of the mammary gland. During milk ejection, release of oxytocin from the neurohypophysis is triggered by synchronized high-frequency bursting of oxytocin neurons. The bursting activity is thought to be facilitated by local somatodendritically release of oxytocin and GABAergic inputs; however, the underlying mechanism remains unclear. Our study on oxytocin receptor (OXTR)-Venus reporter mice identified OXTR-Venus expression in non-oxytocin neurons in the perinuclear zone (PNZ), a region immediately dorsal to the Supraoptic nuclei (SON). This finding leads us to hypothesize that OXTR expressing cells in the PNZ mediate the effect of locally released oxytocin on the facilitation of the bursting activity of oxytocin neurons. The present study aimed to characterize OXTR neurons in the PNZ using reporter mouse lines and electrophysiology with particular emphasis on their plasticity during lactation. Fluorescence microscopy analysis of the PNZ from double reporter mice for OXTR (OXTR-Venus) and GABA (GAD2-mCherry) revealed that the number of OXTR-Venus x GAD2-mCherry neurons in the PNZ was significantly higher in lactating females than in virgin females. Brain slice whole-cell patch clamp recordings of SON oxytocin neurons showed higher frequency of GABA postsynaptic currents in lactating than in virgin females. Moreover, application of OXTR agonist caused greater increase in GABAergic inputs in oxytocin neurons from lactating females. In whole-cell current clamp recordings, the bath application of OXTR agonist, depolarized PNZ OXTR-Venus neurons and triggered action potential firing. The firing frequency of PNZ OXTR-Venus neurons was significantly higher in lactating compared to virgin females. Collectively, these findings suggest that GABAergic neurons projecting to the SON oxytocin neurons express OXTR that are enhanced during lactation. The increased excitability of PNZ OXTR neurons contribute to the heightened GABAergic inputs observed in oxytocin neurons during lactation. Therefore, it is possible that somatodendritically released oxytocin activates OXTR neurons in the PNZ which in turn enhance GABAergic input to SON oxytocin neurons, revealing a state dependent mechanism regulating oxytocin neuron excitability.

Date

7-29-2026

Committee Chair

Teruyama, Ryoichi

LSU Acknowledgement

1

LSU Accessibility Acknowledgment

1

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