Mediodorsal Thalamic Neurons Mirror the Activity of Medial Prefrontal Neurons Responding to Movement and Reinforcement during a Dynamic DNMTP Task

Abstract

The mediodorsal nucleus (MD) interacts with medial prefrontal cortex (mPFC) to support learning and adaptive decision-making. MD receives driver (layer 5) and modulatory (layer 6) projections from PFC and is the main source of driver thalamic projections to middle cortical layers of PFC. Little is known about the activity of MD neurons and their influence on PFC during decision-making. We recorded MD neurons in rats performing a dynamic delayed nonmatching to position (dDNMTP) task and compared results to a previous study of mPFC with the same task (Onos et al., 2016). Criterion event-related responses were observed for 22% (254/1179) of neurons recorded in MD, 237 (93%) of which exhibited activity consistent with mPFC response types. More MD than mPFC neurons exhibited responses related to movement (45% vs. 29%) and reinforcement (51% vs. 27%). MD had few responses related to lever presses, and none related to preparation or memory delay, which constituted 43% of event-related activity in mPFC. Comparison of averaged normalized population activity and population response times confirmed the broad similarity of common response types in MD and mPFC and revealed differences in the onset and offset of some response types. Our results show that MD represents information about actions and outcomes essential for decision-making during dDNMTP, consistent with evidence from lesion studies that MD supports reward-based learning and action-selection. These findings support the hypothesis that MD reinforces task-relevant neural activity in PFC that gives rise to adaptive behavior.

Central thalamic inactivation impairs the expression of action‐ and outcome‐related responses of medial prefrontal cortex neurons in the rat

“…Here, we found evidence that inhibiting central thalamus unilaterally throughout a 60‐m recording session affects the expression of mPFC responses unrelated to memory delays during dDNMTP. These effects seem consistent with both the range of event‐related responses observed in MD neurons during this task (Miller et al., ) and the effects of central thalamic lesions on behavioral measures of reinforcement‐guided responding (Bradfield et al., ; Corbit et al., ; Mair et al., ; Mitchell, ). Of the response types examined, only delay‐related responses did not exhibit a clear trend for reduced expression of task‐related activity during day 2 inactivation compared to day 1 and day 3 (Figure a–g), although differences between response types were not sufficient to produce a significant interaction effect in statistical analyses.…”

“…This effect did not interact with response type examined, muscimol dose tested, the effect of muscimol on background firing rate, or location in the dorsal or ventral mPFC. Most (7/8) of the mPFC response types affected by thalamic inactivation have been observed in MD as well as mPFC neurons of rats performing the dDNMTP (Miller et al., ). There was variability in the extent to which thalamic inactivation reduced event‐related responses in individual mPFC neurons (Figure ), with some showing complete loss of event‐related activity (Figures and ) and others more limited reductions (Figure ).…”

“…See Miller et al. () and Francoeur and Mair () for a more complete discussion of these criteria and response types.…”

“…Miller et al. () report that MD neurons exhibit activity related to lever press actions, movements between levers, and reinforcement events that closely mirror the timing of comparable responses observed in the mPFC in rats performing a dynamic delayed non‐matching to position (dDNMTP) task. These results suggest a broader role for the MD: modulating activity related to actions and outcomes in the PFC.…”

“…These results suggest an important role for the central thalamus in reinforcement‐guided responding that extends beyond working memory. Electrophysiological recordings have confirmed that neurons in MD and IL represent information about task‐relevant stimuli, actions, and outcomes unrelated to memory demands of goal‐directed behaviors (Costello, Zhu, May, Salinas, & Stanford, ; Courtiol & Wilson, ; Han, Lee, Kim, & Jung, ; Matsumoto, Minamimoto, Graybiel, & Kimura, ; Miller, Francoeur, Gibson, & Mair, ; Minamimoto, Hori, & Kimura, ; Oyoshi, Nishio, Asakura, & Ono, ; Tanaka & Kunimatsu, ; Wyder, Massoglia, & Stanford, ).…”