Effects of Hypocretin/Orexin and Major Transmitters of Arousal on Fast Spiking Neurons in Mouse Cortical Layer 6B

Cereb Cortex. 2016 Aug;26(8):3553-62. doi: 10.1093/cercor/bhw158. Epub 2016 May 27.

Abstract

Fast spiking (FS) GABAergic neurons are thought to be involved in the generation of high-frequency cortical rhythms during the waking state. We previously showed that cortical layer 6b (L6b) was a specific target for the wake-promoting transmitter, hypocretin/orexin (hcrt/orx). Here, we have investigated whether L6b FS cells were sensitive to hcrt/orx and other transmitters associated with cortical activation. Recordings were thus made from L6b FS cells in either wild-type mice or in transgenic mice in which GFP-positive GABAergic cells are parvalbumin positive. Whereas in a control condition hcrt/orx induced a strong increase in the frequency, but not amplitude, of spontaneous synaptic currents, in the presence of TTX, it had no effect at all on miniature synaptic currents. Hcrt/orx effect was thus presynaptic although not by an action on glutamatergic terminals but rather on neighboring cells. In contrast, noradrenaline and acetylcholine depolarized and excited these cells through a direct postsynaptic action. Neurotensin, which is colocalized in hcrt/orx neurons, also depolarized and excited these cells but the effect was indirect. Morphologically, these cells exhibited basket-like features. These results suggest that hcrt/orx, noradrenaline, acetylcholine, and neurotensin could contribute to high-frequency cortical activity through an action on L6b GABAergic FS cells.

Keywords: acetylcholine; arousal; neurotensin; noradrenaline; sleep.

MeSH terms

  • Acetylcholine / metabolism
  • Acetylcholine / pharmacology
  • Animals
  • Arousal / physiology
  • GABAergic Neurons / cytology
  • GABAergic Neurons / drug effects
  • GABAergic Neurons / physiology*
  • Glutamate Decarboxylase / genetics
  • Glutamate Decarboxylase / metabolism
  • Green Fluorescent Proteins / genetics
  • Green Fluorescent Proteins / metabolism
  • Membrane Potentials / drug effects
  • Membrane Potentials / physiology
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Neurotensin / metabolism
  • Neurotensin / pharmacology
  • Neurotransmitter Agents / pharmacology
  • Norepinephrine / metabolism
  • Norepinephrine / pharmacology
  • Orexins / metabolism*
  • Orexins / pharmacology
  • Parvalbumins / metabolism
  • Patch-Clamp Techniques
  • Somatosensory Cortex / cytology
  • Somatosensory Cortex / drug effects
  • Somatosensory Cortex / physiology*
  • Tissue Culture Techniques

Substances

  • Neurotransmitter Agents
  • Orexins
  • Parvalbumins
  • Green Fluorescent Proteins
  • Neurotensin
  • Glutamate Decarboxylase
  • glutamate decarboxylase 1
  • Acetylcholine
  • Norepinephrine