Spontaneous Activity of Neostriatal Cholinergic InterneuronsIn Vitro

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Abstract
Neostriatal cholinergic interneurons fire irregularly but tonicallyin vivo. The summation of relatively few depolarizing potentials and their temporal sequence are thought to underlie spike triggering and the irregularity of action potential timing, respectively. In these experiments we used whole-cell, cell-attached, and extracellular recording techniques to investigate the role of spontaneous synaptic inputs in the generation and patterning of action potentials in cholinergic interneuronsin vitro. Cholinergic cells were spontaneously activein vitroat 25 ± 1°C during whole-cell recording from 2 to 3 week postnatal slices and at 35 ± 2°C during cell-attached and extracellular recording from 3 to 4 week postnatal slices. A range of firing frequencies and patterns was observed including regular, irregular, and burst firing. Blockade of AMPA and NMDA receptors altered neither the firing rate nor the pattern, and accordingly, voltage-clamp data revealed a very low incidence of spontaneous EPSCs. GABAAreceptor antagonists were also ineffective in altering the spiking frequency or pattern owing to minimal inhibitory inputin vitro. Functional excitatory and inhibitory inputs to cholinergic cells were disclosed after application of 4-aminopyridine (100 μm), indicating that these synapses are present but not activein vitro. Blockade of D1 or D2 dopamine receptors or muscarinic receptors also failed to influence tonic activity in cholinergic cells. Together these data indicate that cholinergic interneurons are endogenously active and generate action potentials in the absence of any synaptic input. Interspike interval histograms and autocorrelograms generated from unit recordings of cholinergic cellsin vitrowere indistinguishable from those of tonically active neurons recordedin vivo. Irregular spiking is therefore embedded in the mechanism responsible for endogenous activity.