Selective enhancement of excitatory synaptic activity in the rat nucleus tractus solitarius by hypocretin 2

• Published in: Neuroscience 2002-01, Vol.115 (3), p.707-714
• Main Authors: Smith, B.N, Davis, S.F, van den Pol, A.N, Xu, W
• Format: Article
• Language: English
• Subjects: Action Potentials - drug effects; Action Potentials - physiology; Animals; Biological and medical sciences; Central nervous system; Electrophysiology; Excitatory Amino Acid Antagonists - pharmacology; Excitatory Postsynaptic Potentials - drug effects; Excitatory Postsynaptic Potentials - physiology; Fundamental and applied biological sciences. Psychology; GABA Antagonists - pharmacology; GABA-A Receptor Antagonists; glutamate; Immunohistochemistry; Intracellular Signaling Peptides and Proteins; Male; Membrane Potentials - drug effects; Membrane Potentials - physiology; Neural Inhibition - drug effects; Neural Inhibition - physiology; neuropeptide; Neuropeptides - metabolism; Neuropeptides - pharmacology; orexin; Orexins; patch-clamp; Presynaptic Terminals - drug effects; Presynaptic Terminals - metabolism; Rats; Rats, Sprague-Dawley; Receptors, GABA-A - metabolism; Receptors, Glutamate - drug effects; Receptors, Glutamate - metabolism; Solitary Nucleus - drug effects; Solitary Nucleus - metabolism; Synaptic Transmission - drug effects; Synaptic Transmission - physiology; Tetrodotoxin - pharmacology; Up-Regulation - drug effects; Up-Regulation - physiology; vagus; Vertebrates: nervous system and sense organs; Visceral Afferents - drug effects; Visceral Afferents - metabolism; viscerosensory
• ISSN: 0306-4522; 1873-7544
• DOI: 10.1016/S0306-4522(02)00488-8

Hypocretin 2 (orexin B) is a hypothalamic neuropeptide thought to be involved in regulating energy homeostasis, autonomic function, arousal, and sensory processing. Neural circuits in the caudal nucleus tractus solitarius (NTS) integrate viscerosensory inputs, and are therefore implicated in aspects of all these functions. We tested the hypothesis that hypocretin 2 modulates fast synaptic activity in caudal NTS areas that are generally associated with visceral sensation from cardiorespiratory and gastrointestinal systems. Hypocretin 2-immunoreactive fibers were observed throughout the caudal NTS. In whole-cell recordings from neurons in acute slices, hypocretin 2 depolarized 48% and hyperpolarized 10% of caudal NTS neurons, effects that were not observed when Cs + was used as the primary cation carrier. Hypocretin 2 also increased the amplitude of tractus solitarius-evoked excitatory postsynaptic currents (EPSCs) in 36% of neurons and significantly enhanced the frequency of spontaneous EPSCs in most (59%) neurons. Spontaneous inhibitory postsynaptic currents (IPSCs) were relatively unaffected by the peptide. The increase in EPSC frequency persisted in the presence of tetrodotoxin, suggesting a role for the peptide in regulating glutamate release in the NTS by acting at presynaptic terminals. These data suggest that hypocretin 2 modulates excitatory, but not inhibitory, synapses in caudal NTS neurons, including viscerosensory inputs. The selective nature of the effect supports the hypothesis that hypocretin 2 plays a role in modulating autonomic sensory signaling in the NTS.