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.
)in96of106 neurones tested and in all 17 neurones tested the increase in activity (3.4 ± 1.1 to 7.0 ± 1.9 spikes s −1 ) was significantly attenuated (3.0 ± 0.9 to 3.8 ± 1.1 spikes s −1 ) by the selective 5-HT 3 receptor antagonist granisetron. Ionophoretic application of PBG potentiated responses to vagus nerve and cardiopulmonary afferent stimulation, and granisetron significantly attenuated this cardiopulmonary input (20.2 ± 5.7 to 10.6 ± 4.1 spikes burst −1 ) in 9 of 10 neurones tested. Ionophoretic application of AMPA and NMDA also excited NTS neurones and these excitations could be selectively antagonized by the non-NMDA and NMDA receptor antagonists DNQX and AP-5, respectively. At these selective currents, DNQX and AP-5 also attenuated PBG-and cardiopulmonary input-evoked increases in NTS activity. These data are consistent with the hypothesis that vagal inputs, including non-myelinated cardiopulmonary inputs to the NTS, utilize a 5-HT-containing pathway which activates 5-HT 3 receptors. This excitatory response to 5-HT 3 receptor activation may be partly a direct postsynaptic action but part may also be due to facilitation of the release of glutamate which in turn acts on either non-NMDA or NMDA receptors to evoke excitation.
Background Oxytocin (OXT) has been implicated in reproduction and social interactions as well as in the control of digestion and blood pressure. OXT-immunoreactive axons occur in the dorsal vagal complex (DVC; nucleus tractus solitarius, NTS, dorsal motor nucleus of the vagus, DMV, and area postrema, AP), which contains neurons that regulate autonomic homeostasis. The aim of the present work was to provide a systematic investigation of the OXT-immunoreactive innervation of DVC neurons involved in the control of gastrointestinal (GI) function. Methods We studied DMV neurons identified by 1) prior injection of retrograde tracers in the stomach, ileum or cervical vagus or 2) induction of c-fos expression by glucoprivation with 2-deoxyglucose. Another subgroup of DMV neurons was identified electrophysiologically by stimulation of the cervical vagus and then juxtacellularly labelled with biotinamide. We used two- or three-color immunoperoxidase labelling for studies at the light microscopic level. Results Close appositions from OXT-immunoreactive varicosities were found on the cell bodies, dendrites and axons of DMV neurons that projected to the GI tract and that responded to 2-deoxyglucose as well as juxtacellularly-labelled DMV neurons. Double staining for OXT and choline acetyltransferase revealed that OXT innervation was heavier in the caudal and lateral DMV than in other regions. OXT-immunoreactive varicosities also closely apposed a small subset of tyrosine hydroxylase-immunoreactive NTS and DMV neurons. Conclusions and inferences Our results provide the first anatomical evidence for direct OXT-immunoreactive innervation of GI-related neurons in the DVC.
Several forms of learning, including classical conditioning of the eyeblink, depend upon the cerebellum. In examining mechanisms of eyeblink conditioning in rabbits, reversible inactivations of the control circuitry have begun to dissociate aspects of cerebellar cortical and nuclear function in memory consolidation. It was previously shown that post-training cerebellar cortical, but not nuclear, inactivations with the GABAA agonist muscimol prevented consolidation but these findings left open the question as to how final memory storage was partitioned across cortical and nuclear levels. Memory consolidation might be essentially cortical and directly disturbed by actions of the muscimol, or it might be nuclear, and sensitive to the raised excitability of the nuclear neurons following the loss of cortical inhibition. To resolve this question, we simultaneously inactivated cerebellar cortical lobule HVI and the anterior interpositus nucleus of rabbits during the post-training period, so protecting the nuclei from disinhibitory effects of cortical inactivation. Consolidation was impaired by these simultaneous inactivations. Because direct application of muscimol to the nuclei alone has no impact upon consolidation, we can conclude that post-training, consolidation processes and memory storage for eyeblink conditioning have critical cerebellar cortical components. The findings are consistent with a recent model that suggests the distribution of learning-related plasticity across cortical and nuclear levels is task-dependent. There can be transfer to nuclear or brainstem levels for control of high-frequency responses but learning with lower frequency response components, such as in eyeblink conditioning, remains mainly dependent upon cortical memory storage.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.