Temporal processing in the striatum: Interplay between midbrain dopamine neurons and striatal cholinergic interneurons

• Published in: The European journal of neuroscience 2021-04, Vol.53 (7), p.2090-2099
• Main Authors: Martel, Anne‐Caroline, Apicella, Paul
• Format: Article
• Language: English
• Subjects: basal ganglia; Brain; Dopamine; Information processing; Innervation; Interneurons; interval timing; Mesencephalon; Neostriatum; neuronal recording; non‐human primate; rodent; Synaptic plasticity; Temporal perception
• ISSN: 0953-816X; 1460-9568
• DOI: 10.1111/ejn.14741

There has been considerable progress in recent years toward understanding the neuronal mechanisms mediating time perception. Notably, the striatum and its dopamine (DA) input from the ventral midbrain are considered to be central for timing on the scale of hundreds of milliseconds and seconds. The cholinergic interneurons (ChIs) of the striatum provide an extensive local innervation, which closely interacts with striatal DA afferents. Both neuronal systems have been shown to influence synaptic plasticity to shape the transfer of information through the striatum. Given their cooperative role in regulating striatal output pathways, DA and cholinergic inputs may have distinct but complementary roles in timing processes. Electrophysiological recordings from behaving animals have provided evidence that responses of midbrain DA neurons and striatal tonically active neurons (TANs), presumed ChIs, to motivationally relevant events are sensitive to the predicted time of these events; namely, changes in neuronal activity are reduced or absent at times when events are more expected, indicating that temporal aspects of prediction play an important role in the responsiveness of these two neuronal systems. Recently, new findings have further suggested that DA neurons and cholinergic TANs are both involved in the ability to keep track of the elapsed time. These two systems appear to work in parallel in initiating the timing process at the beginning of an interval to be timed. It therefore appears that DA and ChI signaling could participate in striatal processing that is crucial for the control of timing behavior. There is evidence that dopamine inputs from the midbrain and local cholinergic innervation of the striatum are key components of the brain’s timing circuitry. This review summarizes their role, with an emphasis on studies showing that the two neuronal systems exhibit activity changes that can be interpreted as timing signals. These overlapping influences raise the question of whether dopamine and cholinergic signaling convey different messages or act in coordination to control timing behaviors.