Temporal components of cholinergic terminal to dopaminergic terminal transmission in dorsal striatum slices of mice.

ABSTRACT

Striatal dopamine (DA) is critically involved in major brain functions such as motor control and deficits such as Parkinson's disease. DA is released following stimulation by two pathways the nigrostriatal pathway and the cholinergic interneuron (ChI) pathway. The timing of synaptic transmission is critical in striatal circuits, because millisecond latency changes can reverse synaptic plasticity from long-term potentiation to long-term depression in a DA-dependent manner. Here, we determined the temporal components of ChI-driven DA release in striatal slices from optogenetic ChAT-ChR2-EYFP mice. After a light stimulus at room temperature, ChIs fired an action potential with a delay of 2.8 ms. The subsequent DA release mediated by nicotinic acetylcholine (ACh) receptors had a total latency of 17.8 ms, comprising 7.0 ms for cholinergic transmission and 10.8 ms for the downstream terminal DA release. Similar latencies of DA release were also found in striatal slices from wild-type mice. The latency of ChI-driven DA release was regulated by inhibiting the presynaptic vesicular ACh release. Moreover, we describe the time course of recovery of DA release via the two pathways and that of vesicle replenishment in DA terminals. Our work provides an example of unravelling the temporal building blocks during fundamental synaptic terminal-terminal transmission in motor regulation.