Identification of a Group of GABAergic Neurons in the Dorsomedial Area of the Locus Coeruleus.

Publisher: Public Library of Science Country of Publication: United States NLM ID: 101285081 Publication Model: eCollection Cited Medium: Internet ISSN: 1932-6203 (Electronic) Linking ISSN: 19326203 NLM ISO Abbreviation: PLoS One Subsets: MEDLINE

Original Publication: San Francisco, CA : Public Library of Science

GABAergic Neurons/*cytology ; Locus Coeruleus/*cytology; Animals ; Cell Separation ; Cell Tracking ; Electrophysiological Phenomena ; GABAergic Neurons/physiology ; Interneurons/cytology ; Interneurons/physiology ; Locus Coeruleus/physiology ; Male ; Mice ; Mice, Inbred C57BL ; Mice, Transgenic ; Optogenetics ; Patch-Clamp Techniques ; Synaptic Transmission/physiology

The locus coeruleus (LC)-norepinephrine (NE) system in the brainstem plays a critical role in a variety of behaviors is an important target of pharmacological intervention to several neurological disorders. Although GABA is the major inhibitory neurotransmitter of LC neurons, the modulation of LC neuronal firing activity by local GABAergic interneurons remains poorly understood with respect to their precise location, intrinsic membrane properties and synaptic modulation. Here, we took an optogenetic approach to address these questions. Channelrhodopsin (ChR2) in a tandem with the yellow fluorescent protein (YFP) was expressed in GABAergic neurons under the control of glutamic acid decarboxylase 2 (GAD2) promoter. Immediately dorsomedial to the LC nucleus, a group of GABAergic neurons was observed. They had small soma and were densely packed in a small area, which we named the dorsomedial LC or dmLC nucleus. These GABAergic neurons showed fast firing activity, strong inward rectification and spike frequency adaptation. Lateral inhibition among these GABAergic neurons was observed. Optostimulation of the dmLC area drastically inhibited LC neuronal firing frequency, expanded the spike intervals, and reset their pacemaking activity. Analysis of the light evoked inhibitory postsynaptic currents (IPSCs) indicated that they were monosynaptic. Such light evoked IPSCs were not seen in slices where this group of GABAergic neurons was absent. Thus, an isolated group of GABAergic neurons is demonstrated in the LC area, whose location, somatic morphology and intrinsic membrane properties are clearly distinguishable from adjacent LC neurons. They interact with each and may inhibit LC neurons as well as a part of local neuronal circuitry in the LC.

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R01 NS073875 United States NS NINDS NIH HHS; NS073875 United States NS NINDS NIH HHS

Date Created: 20160120 Date Completed: 20160816 Latest Revision: 20201215

20240829

PMC4718449

10.1371/journal.pone.0146470

26785258