Pharmacological blocking of spinal GABAA receptors in monkeys reduces sensory transmission to the spinal cord, thalamus, and cortex
A century of research established that GABA inhibits proprioceptive inputs presynaptically to sculpt spinal neural inputs into skilled motor output. Recent results in mice challenged this theory by showing that GABA can also facilitate action potential conduction in proprioceptive afferents. Here, we tackle this controversy in monkeys, the most human-relevant animal model, and show that GABA<sub>A</sub> receptors (GABA<sub>A</sub>Rs) indeed facilitate sensory inputs to spinal motoneurons and interneurons and that this mechanism also influences sensory transmission to supraspinal centers. We performed causal manipulations of GABA<sub>A</sub>Rs with intrathecal pharmacology in anesthetized monkeys while recording electrical signals in the muscles, spinal cord, thalamus, and cortex. We show that blocking GABA<sub>A</sub>Rs suppresses spinal reflexes to hand muscles, sensory-evoked single-unit firing in the spinal cord, and sensory-evoked potentials in the thalamus and somatosensory cortex. Our results portray a sophisticated picture of presynaptic modulation of sensory inputs by GABA in the spinal cord.
Authors
- Amr A. Mahrous (ORCID: https://orcid.org/0000-0001-9027-1960)
- Josep-Maria Balaguer (ORCID: https://orcid.org/0000-0002-7792-6376)
- Arianna Damiani (ORCID: https://orcid.org/0009-0002-8521-865X)
- Jorge Alvaro Gonzalez-Martinez (ORCID: https://orcid.org/0000-0002-9936-7034)
- Elvira Pirondini (ORCID: https://orcid.org/0000-0002-8078-3951)
- C. J. Heckman (ORCID: https://orcid.org/0000-0002-1324-7278)
- Lucy Liang (ORCID: https://orcid.org/0009-0003-5462-832X)
- Peter C. Gerszten (ORCID: https://orcid.org/0000-0002-1483-6090)
- David J. Bennett
- Daryl P. Fields (ORCID: https://orcid.org/0000-0002-4594-2996)
- Marco Capogrosso (ORCID: https://orcid.org/0000-0002-0975-316X)
- Erinn M. Grigsby (ORCID: https://orcid.org/0000-0002-8378-6488)
- Vahagn Karapetyan
- Jonathan Ho (ORCID: https://orcid.org/0009-0007-9463-6884)
Institutions
- Northwestern University (US)
- Shirley Ryan AbilityLab (US)
- University of Alberta (CA)
- University of Pittsburgh (US)
- Center for the Neural Basis of Cognition (US)
- Women and Children’s Health Research Institute (CA)
- Neurological Surgery (US)
Publication Details
- Journal
- Cell Reports
- Published
- 2024-12-18
- DOI
- https://doi.org/10.1016/j.celrep.2024.115100
- Citations
- 4
- Primary Topic
- Neuroscience and Neuropharmacology Research
- Type
- article
- Field-Weighted Citation Impact
- 1.07
Funders
- Craig H. Neilsen Foundation
- University of Pittsburgh
- National Institutes of Health
- Canadian Institutes of Health Research
- National Institute of Neurological Disorders and Stroke
- Office of Research Infrastructure Programs, National Institutes of Health