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Localization of the Locus Coeruleus in the Mouse Brain
07:44

Localization of the Locus Coeruleus in the Mouse Brain

Published on: March 7, 2019

Orexins cause depolarization via nonselective cationic and K+ channels in isolated locus coeruleus neurons

Yoshinaka Murai1, Tadashi Akaike

  • 1Department of Oral Functional Science (Physiology), Graduate School of Dental Medicine, Hokkaido University, Kita 13 Nishi 7, Kita-ku, Sapporo 060-8586, Japan. murai@den.hokudai.ac.jp

Neuroscience Research
|December 15, 2004
PubMed

Insights

Orexin-A and -B (ORX-A/B) activate locus coeruleus (LC) neurons by increasing firing frequency and depolarization. These effects are mediated by enhanced cationic conductance and inhibited potassium currents in LC neurons.

Area of Science:

  • Neuroscience
  • Neuropharmacology

Background:

  • The locus coeruleus (LC) is a key brainstem nucleus containing noradrenergic neurons.
  • LC neurons are modulated by orexin (ORX) signaling, expressing both orexin receptor-1 and -2.
  • ORX-like immunoreactive axons innervate noradrenergic neurons in the LC.

Purpose of the Study:

  • To investigate the effects of ORX-A and ORX-B on dissociated LC neurons.
  • To elucidate the ionic mechanisms underlying ORX-A/B-induced modulation of LC neuronal activity.

Main Methods:

  • Whole-cell patch clamp electrophysiology was used to record from dissociated LC neurons.
  • Current-clamp recordings assessed changes in membrane potential and firing frequency.
  • Voltage-clamp recordings and ionic manipulations (e.g., Na+ removal) were employed to study ion channel conductances.

Main Results:

  • ORX-A and ORX-B (10(-7) M) induced significant depolarization and increased action potential firing frequency in LC neurons.
  • The ORX-A/B-induced depolarization persisted in the presence of TTX, CNQX, and AP5, indicating a direct postsynaptic effect.
  • ORX-A/B modulated ionic currents, likely by augmenting nonselective cationic conductance and inhibiting sustained K+ currents, with Na+ dependence observed.

Conclusions:

  • ORX-A and ORX-B enhance the excitability of LC neurons.
  • The observed depolarization and increased firing are attributed to alterations in cationic and potassium conductances.
  • Orexin signaling plays a significant role in regulating noradrenergic LC neuron activity.

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