Isoniazid-induced reduction in GABAergic neurotransmission alters the function of the cerebellar cortical circuit
Neuroscience. 2008-06-01; 154(2): 710-719
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1. Neuroscience. 2008 Jun 23;154(2):710-9. doi: 10.1016/j.neuroscience.2008.02.024.
Epub 2008 Feb 29.
Isoniazid-induced reduction in GABAergic neurotransmission alters the function of
the cerebellar cortical circuit.
Carta M(1), Murru L, Barabino E, Talani G, Sanna E, Biggio G.
(1)Department of Experimental Biology Bernardo Loddo, Section of Neuroscience,
University of Cagliari, Cittadella Universitaria, SS 554, Km 4,500, Monserrato
The cerebellar cortex contributes to the control of movement, coordination, and
certain cognitive functions. The cerebellar network is composed of five different
types of neurons that are wired together in a repetitive module. Given that four
of these five neurons synthesize and release GABA, this inhibitory
neurotransmitter plays a central role in regulation of the excitability and
correct functioning of the cerebellar cortex. We have now used isoniazid, an
inhibitor of glutamic acid decarboxylase, the enzyme responsible for the
synthesis of GABA, to evaluate the contribution of GABAergic transmission in
different types of cerebellar cortical neurons to the functioning of the
cerebellar circuit. Parasagittal cerebellar slices were prepared from 28- to
40-day-old male rats and were subjected to patch-clamp recording in the voltage-
or current-clamp mode. Exposure of the tissue slices to isoniazid (10 mM)
resulted in a decrease in the level of GABAergic transmission in Purkinje cells
and a consequent increase in the firing rate of spontaneous action potentials
that was apparent after 40 min. In granule neurons, isoniazid reduced both tonic
and phasic GABAergic currents and thereby altered the flow of information across
the cerebellar cortex. Our data support the notion that the amount of GABA at the
synaptic level is a major determinant of the excitability of the cerebellar
cortex, and they suggest that isoniazid may be a useful tool with which to study
the function of the cerebellar network.
PMID: 18456415 [Indexed for MEDLINE]