Experience‐related enhancements in striatal temporal encoding

Abstract

Temporal control of action is key for a broad range of behaviors and is disrupted in human diseases such as Parkinson's disease and schizophrenia. A brain structure that is critical for temporal control is the dorsal striatum. Experience and learning can influence dorsal striatal neuronal activity, but it is unknown how these neurons change with experience in contexts which require precise temporal control of movement. We investigated this question by recording from medium spiny neurons (MSNs) via dorsal striatal microelectrode arrays in mice as they gained experience controlling their actions in time. We leveraged an interval timing task optimized for mice which required them to “switch” response ports after enough time had passed without receiving a reward. We report three main results. First, we found that time‐related ramping activity and response‐related activity increased with task experience. Second, temporal decoding by MSN ensembles improved with experience and was predominantly driven by time‐related ramping activity. Finally, we found that a subset of MSNs had differential modulation on error trials. These findings enhance our understanding of dorsal striatal temporal processing by demonstrating how MSN ensembles can evolve with experience. Our results can be linked to temporal habituation and illuminate striatal flexibility during interval timing, which may be relevant for human disease.

Alpha-synuclein pre-formed fibrils injected into prefrontal cortex primarily spread to cortical and subcortical structures and lead to isolated behavioral symptoms

“…Fibrillar and "lewy-neurite-like" structures were only seen in PFF injected mice, and this was confirmed by confocal microscopy. Second, we did not include a group of young mice to determine whether our lack of behavioral change was primarily due to age-related decline in cognitive function or interval timing, which has been observed previously (Beas et al, 2017;Gür et al, 2020), although the interval timing behavior presented here is similar to previously published work from our group using healthy, young C57BL/6 mice (Bruce et al, 2021). Third, our measures of interval timing and behavioral flexibility do not fully interrogate cognitive dysfunctions related to PDD and LBD and it is possible that other cognitive behaviors such as attention or impulse control were negatively affected by PFC PFF injections.…”

“…Interval Timing Switch Task: All mice were trained to perform an interval timing switch task described in detail previously (Balci et al, 2008;Bruce et al, 2021;Larson et al, 2022;Weber et al, (which was not certified by peer review) is the author/funder. All rights reserved.…”

Glycolysis-enhancing α1-adrenergic antagonists modify cognitive symptoms related to Parkinson’s disease

“…We trained 29 mice starting at ∼14–16 weeks of age to perform an interval timing task in which mice switched from one nosepoke to another based on internal timing cues to get a food reward (Fig. 1A; Balci et al, 2008; Bruce et al, 2021; Larson et al, 2022). In these animals, we surgically injected vehicle (0.03% ascorbic acid) as a surgical control or 6-OHDA to deplete dopamine in the VTA, which we have previously shown impairs interval timing (Kim et al, 2017; Narayanan et al, 2012; Parker et al, 2015).…”

“…Interval Timing Switch Task: The interval timing switch task is designed to capture an animal's internal representation of time (Balci et al, 2008;Bruce et al, 2021;Larson et al, 2022;Tosun et al, 2016), as in other interval timing tasks (Emmons et al, 2020;Narayanan et al, 2012). Mice are trained to switch from a short to a long nosepoke after approximately 6 seconds.…”

Mice expressing P301S mutant human tau have deficits in interval timing

“…The switch interval timing task (Fig. 1A) assesses an animal’s ability to control actions based on an internal representation of time (Balci et al, 2008; Bruce et al, 2021; Tosun et al, 2016). Mice were trained to perform the task in operant chambers (MedAssociates, St. Albans, VT) placed in sound attenuating cabinets.…”