Temporal learning among prefrontal and striatal ensembles

Abstract

1Behavioral flexibility requires the prefrontal cortex and striatum. Here, we investigate neuronal 2 ensembles in the medial frontal cortex (MFC) and the dorsomedial striatum (DMS) during one 3 form of behavioral flexibility: learning a new temporal interval. We studied corticostriatal 4 neuronal activity as rodents trained to respond after a 12-second fixed interval (FI12) learned to 5 respond at a shorter 3-second fixed interval (FI3). On FI12 trials, we discovered time-related 6 ramping was reduced in the MFC but not in the DMS in two-interval vs. one-interval sessions. 7 We also found that more DMS neurons than MFC neurons exhibited differential interval-related 8 activity on the first day of two-interval performance. Finally, MFC and DMS ramping was 9 similar with successive days of two-interval performance but DMS temporal decoding increased 10 on FI3 trials. These data suggest that the MFC and DMS play distinct roles during temporal 11 learning and provide insight into corticostriatal circuits. 13 Behavioral flexibility requires learning to adapt to uncertainty. Two forebrain structures 14 critical for flexibility are the prefrontal cortex and striatum (Fuster, 2008; Kehagia et al., 2010). 15 Prefrontal cortical neurons densely innervate the striatum (Gabbott et al., 2005; Wall et al., 2013) 16 and disruptions of either structure profoundly impact the learning of new goals, rules, and 17 strategies (Hart et al., 2018; Ragozzino, 2007). Dysfunctional corticostriatal circuits and 18 connectivity are implicated in a range of psychiatric and neurological disorders (Deutch, 1993; 19 Shepherd, 2013). However, the relative roles of prefrontal and striatal networks during 20 behavioral flexibility are unclear. 21One task that provides an ideal window into behavioral flexibility is interval timing, 22 which requires participants to estimate an interval of several seconds via a motor response. 23Across species, interval timing requires the prefrontal cortex and striatum (Coull et al., 2011; Merchant and de 25 Lafuente, 2014). Work from our group and others has shown that both prefrontal and striatal 26 neurons encode temporal information via 'time-related ramping' activity-or monotonic changes 27 in firing rate over a temporal interval (Bakhurin et al., 2017; Donnelly et al., 2015; Emmons et 28 al., 2017; Kim et al., 2018; Narayanan, 2016; Wang et al., 2018). Our past work suggested that 29 ramping activity in neurons of the medial frontal cortex (MFC) and the dorsomedial striatum 30 (DMS) is very similar, with ~40% of neurons in each area exhibiting such activity (Emmons et 31 al., 2017). We have also found that MFC inactivation attenuates DMS ramping (Emmons et al., 32 2019, 2017) and that MFC stimulation is sufficient to increase DMS ramping (Emmons et al., 33 2019). These data suggest that DMS ramping is closely linked to MFC ramping and suggest the 34 hypothesis that MFC and DMS ensembles respond similarly as animals learn new temporal 35 intervals. By contrast, recordings from prima...

Experience‐related enhancements in striatal temporal encoding

“…Our findings are broadly consistent with our previous work (Emmons et al., 2016, 2017, 2019, 2020). In one of these studies with well‐trained animals (Emmons et al., 2020), we found that striatal time‐related ramping was stable as highly trained rats learned a new, shorter fixed interval over 3 days. By contrast, in this study, we compared striatal temporal encoding just after mice acquired a switch interval timing task and again after ~10 days of experience.…”

Time-Encoding Migrates from Prefrontal Cortex to Dorsal Striatum During Learning of a Self-Timed Response Duration Task

“…Hence, animals may have habituated with the action (nose poking), and the only new contingency introduced in the task was the wait time. In this sense, our results agree with previous results implicating the mPFC in top-down control of executive tasks, including behavioral switching learning 28–31 .…”

“…Finally, our results agree with recent neuronal recordings during learning of a new interval in a fixed-interval task28. They showed that the medial prefrontal cortex and striatum play different rules on temporal and behavior flexibility.…”

Functional Architecture of Executive Control and Associated Event-Related Potentials

“…We conjecture that the appearance of the visual target initiates the first ramping activity, timing the interval until SSRT. This can provide a substrate for fronto-striatal pathways to learn, update, or validate the temporal structure of the task 55–57 .…”

“…Further research is needed to clarify this projection. Also, these neurons can contribute to fronto-striatal pathways to learn and update the temporal structure of the task 57,58,59 . Axon terminals from SEF are dense in the caudate nucleus 43 , arising from pyramidal neurons in L3 and L5 60,61,62 .…”