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Neurosteroids involved in regulating inhibition in the inferior colliculus

Citation

Saalmann, YB and Morgan, IG and Calford, MB, Neurosteroids involved in regulating inhibition in the inferior colliculus, Journal of Neurophysiology, 96, (6) pp. 3064-3073. ISSN 0022-3077 (2006) [Refereed Article]

DOI: doi:10.1152/jn.00786.2006

Abstract

Fast inhibitory neurotransmission in the brain is largely mediated by the γ-aminobutyric acid-type A (GABAA) receptor. The 3α,5α-reduced neurosteroids (e.g., allopregnanolone) are the most potent endogenous modulators of the GABAA receptor. Although it is known that 3α,5α-reduced neurosteroid levels change during stress or depression and over the estrus cycle, a basic physiological role consistent with their pharmacological action remains elusive. We used the unique architecture of the auditory midbrain to reveal a role for 3α,5α- reduced neurosteroids in regulating inhibitory efficacy. After blocking the massive GABAergic projection from the dorsal nucleus of the lateral lemniscus (DNLL) to the contralateral central nucleus of the inferior colliculus (ICC) in anesthetized rats, a reactive increase in the efficacy of other inhibitory circuits in the ICC (separable because of the dominant ear that drives each circuit) was demonstrated with physiological measures - single-neuron activity and a neural-population-evoked response. This effect was prevented by blocking 3α,5α-reduced neurosteroid synthesis with a 5α-reductase inhibitor: finasteride. Immunohistochemistry confirmed that the DNLL blockade induced an increase in 3α,5α-reduced neurosteroids in the contralateral ICC. This study shows that when GABAergic inhibition is reduced, the brain compensates within minutes by locally increasing synthesis of neurosteroids, thereby balancing excitatory and inhibitory inputs in complex neural circuits. Copyright © 2006 The American Physiological Society.

Item Details

Item Type:Refereed Article
Keywords:3alpha hydroxy 5alpha pregnan 20 one; 4 aminobutyric acid A receptor; finasteride; neurosteroid; animal cell; animal experiment; animal tissue; article; brain region; controlled study; drug effect; estrus cycle; evoked auditory response
Research Division:Medical and Health Sciences
Research Group:Neurosciences
Research Field:Neurology and Neuromuscular Diseases
Objective Division:Health
Objective Group:Clinical Health (Organs, Diseases and Abnormal Conditions)
Objective Field:Nervous System and Disorders
Author:Calford, MB (Professor Mike Calford)
ID Code:91304
Year Published:2006
Web of Science® Times Cited:12
Deposited By:Research Division
Deposited On:2014-05-13
Last Modified:2014-05-13
Downloads:0

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