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The role of spinal GABAergic circuits in the control of phrenic nerve motor output
Journal article   Open access   Peer reviewed

The role of spinal GABAergic circuits in the control of phrenic nerve motor output

Vitaliy Marchenko, Michael G Z Ghali and Robert F Rogers
American journal of physiology. Regulatory, integrative and comparative physiology, v 308(11), pp R916-R926
01 Jun 2015
DOI: https://doi.org/10.1152/ajpregu.00244.2014
PMID: 25833937
Featured in Collection :   UN Sustainable Development Goals @ Drexel
url
https://doi.org/10.1152/ajpregu.00244.2014View
Published, Version of Record (VoR)Open Access (License Unspecified),  Open

Abstract

Action Potentials Animals Anterior Horn Cells - metabolism Down-Regulation gamma-Aminobutyric Acid - metabolism Glutamate Decarboxylase - genetics Glutamate Decarboxylase - metabolism Interneurons - metabolism Male Microinjections Phenotype Phrenic Nerve - metabolism Rats, Sprague-Dawley Respiration Respiratory Muscles - innervation RNA Interference RNA, Small Interfering - administration & dosage Synaptic Transmission Time Factors
While supraspinal mechanisms underlying respiratory pattern formation are well characterized, the contribution of spinal circuitry to the same remains poorly understood. In this study, we tested the hypothesis that intraspinal GABAergic circuits are involved in shaping phrenic motor output. To this end, we performed bilateral phrenic nerve recordings in anesthetized adult rats and observed neurogram changes in response to knocking down expression of both isoforms (65 and 67 kDa) of glutamate decarboxylase (GAD65/67) using microinjections of anti-GAD65/67 short-interference RNA (siRNA) in the phrenic nucleus. The number of GAD65/67-positive cells was drastically reduced on the side of siRNA microinjections, especially in the lateral aspects of Rexed's laminae VII and IX in the ventral horn of cervical segment C4, but not contralateral to microinjections. We hypothesize that intraspinal GABAergic control of phrenic output is primarily phasic, but also plays an important role in tonic regulation of phrenic discharge. Also, we identified respiration-modulated GABAergic interneurons (both inspiratory and expiratory) located slightly dorsal to the phrenic nucleus. Our data provide the first direct evidence for the existence of intraspinal GABAergic circuits contributing to the formation of phrenic output. The physiological role of local intraspinal inhibition, independent of descending direct bulbospinal control, is discussed.

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30 citations in Web of Science
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