Oxytocin Enhances Cranial Visceral Afferent Synaptic Transmission to the Solitary Tract Nucleus

Abstract

Cranial visceral afferents travel via the solitary tract (ST) to contact neurons within the ST nucleus (NTS)and activate homeostatic reflexes. Hypothalamic projections from the paraventricular nucleus (PVN) release oxytocin (OT) to modulate visceral afferent communication with NTS neurons. However, the cellular mechanisms through which OT acts are poorly understood. Here, we electrophysiologically identified second-order NTS neurons in horizontal brainstem slices by their low-jitter, ST-evoked glutamatergic EPSCs. OT increased the frequency of miniature EPSCs in half of the NTS second-order neurons (13/24) but did not alter event kinetics or amplitudes. These actions were blocked by a selective OT receptor antagonist. OT increased the amplitude of ST-evoked EPSCs with no effect on event kinetics. Variance-mean analysis of ST-evoked EPSCs indicated OT selectively increased the release probability of glutamate from the ST afferent terminals. In OT-sensitive neurons, OT evoked an inward holding current and increased input resistance. The OT-sensitive current reversed at the K ϩ equilibrium potential. In in vivo studies, NTS neurons excited by vagal cardiopulmonary afferents were juxtacellularly labeled with Neurobiotin and sections were stained to show filled neurons and OT-immunoreactive axons. Half of these physiologically characterized neurons (5/10) showed close appositions by OT fibers consistent with synaptic contacts. Electron microscopy of medial NTS found immunoreactive OT within synaptic boutons. Together, these findings suggest that OT released from PVN axons acts on a subset of second-order neurons within medial NTS to enhance visceral afferent transmission via presynaptic and postsynaptic mechanisms.

Distinct Calcium Sources Support Multiple Modes of Synaptic Release from Cranial Sensory Afferents

“…These synchronous EPSCs conform to parabolic variance-mean amplitude relationships indicating that ST axons have a high probability of release (ϳ90% in 2 mM external Ca 2ϩ ) and activate an average of 18 active zone release sites (Bailey et al, 2006b;Andresen and Peters, 2008;Peters et al, 2008). Interestingly, even multiple convergent ST inputs perform independently (Peters et al, 2011;McDougall and Andresen, 2013), which implies that ST synaptic release zones are quite selfcontained with clear spatial delimitations.…”

“…؊ afferents ST afferents lacking TRPV1 have myelinated axons (Jin et al, 2004), are relatively rare, and have indistinguishable synchronous release compared with TRPV1 ϩ afferents (Andresen and Peters, 2008). Neurons receiving these afferents serve as a natural "control" for comparison to the C-fiber TRPV1 ϩ afferent phenotype.…”

Central Vagal Afferent Endings Mediate Reduction of Food Intake by Melanocortin-3/4 Receptor Agonist

“…Thus, central vagal afferent endings not only are conduits of signals arriving from the gut, but also may be directly engaged by signals converging onto the NTS from other brain areas. Several anorexic and orexigenic signals have been shown previously to modulate neurotransmission from central vagal afferent endings, including oxytocin (Peters et al, 2008), ghrelin (Cui et al, 2011), and serotonin (Cui et al, 2012). Whether these and other signals also influence food intake by engaging the gut-to-brain circuit via direct activation of central vagal afferent endings merits future investigation.…”

Afferent signaling drives oxytocinergic preautonomic neurons and mediates training-induced plasticity

“…Oxytocinergic terminals are evenly distributed throughout the NTS (23,35), and OT-immunoreactive axons are closely apposed, suggesting synaptic contacts, with second-order NTS neurons (35). Peters et al (35) showed that OT released from OTergic axons acts on a subset of second-order NTS neurons to enhance afferent visceral transmission via presynaptic (i.e., increased probability for glutamate release) and postsynaptic (increased inward current by closure of K ϩ channels) mechanisms. Therefore, activation of PVN-NTS OTergic projections causes a slowing of HR via at least two different mechanisms: modulation of afferent signaling and a direct effect of depolarizing and exciting NTS neurons.…”