Distinct dampening effects of progesterone on the activity of nucleus tractus solitarus neurons in rat pups

NEW FINDINGS

What is the central question of the study? Progesterone is considered as a respiratory stimulant drug, but its effect on medullary respiratory neurons are poorly documented. We investigated whether progesterone alters spontaneous activity of neurons in the nucleus of the solitary tract (NTS). What is the main finding and its importance? In NTS neurons, progesterone decreases the action potential firing frequency in response to current injections and the amplitude of excitatory postsynaptic currents (EPSC). Based on the established neuroprotective effect of progesterone against excitotoxicity resulting from insults, this inhibitory effect likely reflects inhibition of ion fluxes. These results are important as they further our understanding of the mechanisms underlying the diversity of the respiratory effects of progesterone.

Abstract

Progesterone is known to stimulate breathing, but its actions on the respiratory control system have received limited attention. We addressed this issue at the cellular level by testing the hypothesis that progesterone augments excitatory currents at the level of the NTS. Medullary slices from juvenile male rats (14–17 days of age) containing the commissural region of the NTS (NTScom) were incubated with progesterone (1 μM) or vehicle (DMSO 0.004%) for 60 min. We performed whole‐cell voltage clamp recordings of spontaneous excitatory postsynaptic currents (EPSCs) in the NTScom, and determined membrane properties by applying depolarizing current steps. By comparison with vehicle‐treated cells, progesterone exposure attenuates the firing frequency response to current injection and reduces the EPSC amplitude without modifying the EPSC frequency or the basal membrane properties. These data do not support our hypothesis as they indicate that incubation with progesterone attenuates intrinsic action potential generation and inhibits excitatory synaptic inputs in the NTS. Since these results are more in line with the protective effect of progesterone against excitotoxicity resulting from various insults, we propose that progesterone acts via inhibition of ionic flux.

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