Endogenous XXXX modulates GABAergic transmission to granule cells in adult rat cerebellum.

@entity1382 @entity1246 @entity4524 @entity842 @entity934
@entity842 (NO) is a gaseous neurotransmitter which plays an important role in neuronal signalling and plasticity throughout the brain. In the cerebellum, @entity1382 ( @entity1382 ) is expressed in parallel fibres and within the internal granule cell layer (IGL). During development there are changes in @entity1382 concentration, distribution and activity within the IGL, suggesting NO may play a role in IGL function. Therefore, the actions of NO in the IGL were investigated. The similar actions of a range of @entity1382 inhibitors and NO scavengers strongly suggested the presence of a tonic level of endogenous NO in the IGL. Both the neuronal and inducible forms of @entity1382 appeared to be sources of this endogenous NO. The effects observed following a reduction in the concentration of endogenous NO were consistent with enhanced granule cell GABAA receptor activation. For example, a reduction in NO concentration led to an increase in the frequency of action potential-dependent phasic GABAergic inhibitory postsynaptic currents (IPSCs) and produced a @entity4524 -insensitive GABAA receptor-mediated current. A direct action of NO on Golgi cell membrane potential and input resistance accounted for the increase in the frequency of phasic @entity1246 release. The mechanism underlying the tonic @entity1246 current is unclear but does not appear to be via the modulation of @entity1246 uptake or the activation of nicotinic @entity934 receptors. NO is a potentially novel mechanism for tuning GABAergic signalling to granule cells and therefore modulating the throughput of an important cerebellar circuit.
