Expression of GABAA receptor subunits in rat brainstem auditory pathways: cochlear nuclei, superior olivary complex and nucleus of the lateral lemniscus

Campos, M. L.; Cabo, Carlos de; Wisden, William; Juı́z, José M.; Merlo, Daniela

doi:10.1016/s0306-4522(00)00525-x

Cited by 53 publications

(39 citation statements)

References 68 publications

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“…It seems that both F and LF neurons may be GABAergic (Roberts and Ribak, 1987;Merchan et al, 2005). The rat IC neurons possess GABA A , GABA B and glycine receptors (Bowery et al, 1987;Edgar and Schwartz, 1990;Vaughn et al, 1996;Campos et al, 2001). The GABA B receptors seem to be more abundant in the DCIC, RCIC and LCIC than in the CIC (Jamal et al, 2011(Jamal et al, , 2012.…”

Section: Neurochemistry and Electrophysiological Responses And Functimentioning

confidence: 98%

Auditory System

Malmierca

2015

The Rat Nervous System

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Section: Neurochemistry and Electrophysiological Responses And Functimentioning

confidence: 98%

Auditory System

Malmierca

2015

The Rat Nervous System

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“…It is also very tempting to analyze the role of Cl À transporters in shaping inhibitory synapses in the NLL-IC circuitry. NLL neurons receive GABAergic and glycinergic input (Campos et al, 2001;Riquelme et al, 2001;Pecka et al, 2007;Kutscher and Covey, 2009), and they are also a major source of inhibition to the IC (Shneiderman et al, 1988(Shneiderman et al, , 1993Kelly and Li, 1997;Vater et al, 1997;Batra and Fitzpatrick, 2002;Malmierca, 2003). Moreover, 20e25% of IC neurons are GABAergic (Oliver et al, 1994;Merchán et al, 2005) and provide input to the medial geniculate body (Ito et al, 2009).…”

Section: Areas For Further Researchmentioning

confidence: 99%

Chloride cotransporters, chloride homeostasis, and synaptic inhibition in the developing auditory system

et al. 2011

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“…GABARs containing α4 and δ subunits are expressed in many brain regions 14,15 , but α6 is found in only two types of neurons (cerebellar granule cells and granule cells in the cochlear nucleus) and is expressed together with δ only in cerebellar granule cells 14,16,17 . In granule cells α6 and δ combine with β subunits Correspondence should be addressed to M.W.…”

Section: Introductionmentioning

confidence: 99%

Alcohol-induced motor impairment caused by increased extrasynaptic GABAA receptor activity

et al. 2005

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Neuronal mechanisms underlying alcohol intoxication are unclear. We find that alcohol impairs motor coordination by enhancing tonic inhibition mediated by a specific subtype of extrasynaptic GABA A receptor (GABAR), α6β3δ, expressed exclusively in cerebellar granule cells. In recombinant studies, we characterize a naturally occurring single-nucleotide polymorphism that causes a single amino acid change (R100Q) in α6 (encoded in rats by the Gabra6 gene). We show that this change selectively increases alcohol sensitivity of α6β3δ GABARs. Behavioral and electrophysiological comparisons of Gabra6 100R/100R and Gabra6 100Q/100Q rats strongly suggest that alcohol impairs motor coordination by enhancing granule cell tonic inhibition. These findings identify extrasynaptic GABARs as critical targets underlying low-dose alcohol intoxication and demonstrate that subtle changes in tonic inhibition in one class of neurons can alter behavior.Humans have been consuming alcohol for thousands of years, and the use of alcoholic beverages pervades human culture and society and can have substantial health effects 1 . Different mechanisms by which ethanol might depress brain function have been proposed based on ethanol's ability to modulate a wide variety of ion channels 2-4 , neurotransmitter receptors 5-10 and transporters 11 . Among these diverse targets, however, GABARs are arguably the most attractive candidates. This is in part because other classes of known GABAR modulators such as benzodiazepines, barbiturates and certain anesthetics lead to behavioral effects that closely resemble ethanol intoxication. Yet despite strong evidence implicating GABARs in ethanol's action, critical details remain unclear. For instance, although it is known that native GABARs are heteropentamers assembled from 19 possible subunits 12,13 , it has not been possible to link the activity of particular GABAR subunits to changes in behavioral sensitivity to ethanol.Recent studies suggest that specific combinations of GABAR subunits (those containing α4β3δ and α6β3δ) are uniquely sensitive to ethanol, showing dose dependencies that mirror blood alcohol levels associated with intoxication in humans 9,10 . GABARs containing α4 and δ subunits are expressed in many brain regions 14,15 , but α6 is found in only two types of neurons (cerebellar granule cells and granule cells in the cochlear nucleus) and is expressed together with δ only in cerebellar granule cells 14,16,17 . In granule cells α6 and δ combine with β subunits Correspondence should be addressed to M.W. (mwallner@mednet.ucla.edu) or T.S.O. (otist@ucla.edu). 3 These authors contributed equally to this work. COMPETING INTERESTS STATEMENTThe authors declare that they have no competing financial interests. We set out to examine whether such extrasynaptic GABARs containing α6 and δ subunits account for behavioral effects of ethanol at moderately intoxicating doses. To link these particular GABARs to behavioral sensitivity, we first characterized a naturally occurring single-nucleotide polymo...

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Expression of GABAA receptor subunits in rat brainstem auditory pathways: cochlear nuclei, superior olivary complex and nucleus of the lateral lemniscus

Cited by 53 publications

References 68 publications

Auditory System

Auditory System

Chloride cotransporters, chloride homeostasis, and synaptic inhibition in the developing auditory system

Alcohol-induced motor impairment caused by increased extrasynaptic GABAA receptor activity

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