1. Distinct Modes of Presynaptic Inhibition of Cutaneous Afferents and Their Functions in Behavior.
- Author
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Zimmerman AL, Kovatsis EM, Pozsgai RY, Tasnim A, Zhang Q, and Ginty DD
- Subjects
- Animals, Bicuculline analogs & derivatives, Bicuculline pharmacology, Discrimination, Psychological, GABA-A Receptor Antagonists pharmacology, Hyperesthesia genetics, Mice, Nerve Tissue Proteins metabolism, Neurons, Afferent metabolism, Pyridazines pharmacology, Receptors, GABA-A metabolism, Receptors, N-Methyl-D-Aspartate metabolism, Spinal Cord Dorsal Horn, Behavior, Animal, Nerve Tissue Proteins genetics, Neural Inhibition, Presynaptic Terminals metabolism, Receptors, GABA-A genetics, Receptors, N-Methyl-D-Aspartate genetics, Sensory Receptor Cells metabolism, Skin innervation, Touch
- Abstract
Presynaptic inhibition (PSI) of primary sensory neurons is implicated in controlling gain and acuity in sensory systems. Here, we define circuit mechanisms and functions of PSI of cutaneous somatosensory neuron inputs to the spinal cord. We observed that PSI can be evoked by different sensory neuron populations and mediated through at least two distinct dorsal horn circuit mechanisms. Low-threshold cutaneous afferents evoke a GABA
A -receptor-dependent form of PSI that inhibits similar afferent subtypes, whereas small-diameter afferents predominantly evoke an NMDA-receptor-dependent form of PSI that inhibits large-diameter fibers. Behaviorally, loss of either GABAA receptors (GABAA Rs) or NMDA receptors (NMDARs) in primary afferents leads to tactile hypersensitivity across skin types, and loss of GABAA Rs, but not NMDARs, leads to impaired texture discrimination. Post-weaning age loss of either GABAA Rs or NMDARs in somatosensory neurons causes systemic behavioral abnormalities, revealing critical roles of two distinct modes of PSI of somatosensory afferents in adolescence and throughout adulthood., (Copyright © 2019 Elsevier Inc. All rights reserved.)- Published
- 2019
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