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

B. N. Smith, S. F. Davis, A. N. Van Den Pol, W. Xu

Research output: Contribution to journalArticlepeer-review

64 Scopus citations


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.

Original languageEnglish
Pages (from-to)707-714
Number of pages8
Issue number3
StatePublished - Dec 9 2002

Bibliographical note

Funding Information:
This research was supported by funds from the National Science Foundation (B.N.S. and A.N.v.d.P.), the American Heart Association (B.N.S.), and the Louisiana Board of Regents (B.N.S.). We thank D. Liu for technical assistance and to Dr. F.E. Dudek for his contribution to preliminary aspects of the study.


  • Glutamate
  • Neuropeptide
  • Orexin
  • Patch-clamp
  • Vagus
  • Viscerosensory

ASJC Scopus subject areas

  • General Neuroscience


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