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

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

Prefrontal Neurons Encode Actions and Outcomes in Conjunction with Spatial Location in Rats Performing a Dynamic Delayed Non-Match to Position Task

To respond adaptively to change organisms must utilize information about recent events and environmental context to select actions that are likely to produce favorable outcomes. We developed a dynamic delayed nonmatching to position task to study the influence of spatial context on event-related activity of medial prefrontal cortex neurons during reinforcement-guided decision-making. We found neurons with responses related to preparation, movement, lever press responses, reinforcement, and memory delays. Combined event-related and video tracking analyses revealed variability in spatial tuning of neurons with similar event-related activity. While all correlated neurons exhibited spatial tuning broadly consistent with relevant task events, for instance reinforcement-related activity concentrated in locations where reinforcement was delivered, some had elevated activity in more specific locations, for instance reinforcement-related activity in one of several locations where reinforcement was delivered. Timing analyses revealed a limited set of distinct response types with activity time-locked to critical behavioral events that represent the temporal organization of dDNMTP trials. Our results suggest that reinforcement-guided decision-making emerges from discrete populations of medial prefrontal neurons that encode information related to planned or ongoing movements and actions and anticipated or actual action-outcomes in conjunction with information about spatial context

The neurobiology of thalamic amnesia: Contributions of medial thalamus and prefrontal cortex to delayed conditional discrimination

Although medial thalamus is well established as a site of pathology associated with global amnesia, there is uncertainty about which structures are critical and how they affect memory function. Evidence from human and animal research suggests that damage to the mammillothalamic tract and the anterior, mediodorsal (MD), midline (M), and intralaminar (IL) nuclei contribute to different signs of thalamic amnesia. Here we focus on MD and the adjacent M and IL nuclei, structures identified in animal studies as critical nodes in prefrontal cortex (PFC)-related pathways that are necessary for delayed conditional discrimination. Recordings of PFC neurons in rats performing a dynamic delayed non-matching-to position (DNMTP) task revealed discrete populations encoding information related to planning, execution, and outcome of DNMTP-related actions and delay-related activity signaling previous reinforcement. Parallel studies recording the activity of MD and IL neurons and examining the effects of unilateral thalamic inactivation on the responses of PFC neurons demonstrated a close coupling of central thalamic and PFC neurons responding to diverse aspects of DNMTP and provide evidence that thalamus interacts with PFC neurons to give rise to complex goal-directed behavior exemplified by the DNMTP task

Variability in spatial heat maps, raster-plots, and peri-event time histograms (PETH) for neurons with movement I responses.

<p>PETHs and raster plots are aligned with delay lever presses to show increased activity before and after this response. The 99% confidence is indicated on PETHs in blue. Raster plots show event markers for sample (blue), delay (red), and choice (yellow) lever presses. Heat maps are oriented as in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0149019#pone.0149019.g005" target="_blank">Fig 5</a>, with activity in spikes/s indicated on the scale to the left of each plot and locations of base levers marked with small white arrows.</p

Broadly distributed and spatially-restricted firing patterns for neurons without criterion event-related responses.

<p>Spatial heat maps show the distribution of activity of neurons with broadly distributed (A to D) and restricted (E to H) spatial firing fields. Maps are oriented and neural activity is plotted as spikes/s as indicated by the scale to the left of each plot as in Figs <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0149019#pone.0149019.g005" target="_blank">5</a>–<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0149019#pone.0149019.g008" target="_blank">8</a>.</p

Timing of different response types during DNMTP trials.

<p>The average (thick bar) and SEM (thin bar) duration of increased activity is plotted relative to start, sample, delay, and choice lever presses. Responses were measured based on when activity was above the 99% confidence interval (see <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0149019#pone.0149019.g003" target="_blank">Fig 3</a>). These analyses were restricted to responses sufficiently robust to remain consistently outside this limit during periods of elevated activity. Results are plotted for preparatory (Prep, N = 25 for start and N = 19 for delay responses), movement I (Move 1, N = 55), movement II (Move 2, N = 12), lever press (Lev, N = 24), base lever press (Base Lev, N = 13), post-reinforcement (Post R, N = 8), reinforcement excitation (R Excit, N = 31), reinforcement anticipation (R Antic, N = 17), error (N = 4), and delay (N = 19). Preparatory and movement responses are plotted relative to the lever presses they preceded. Reinforcement, error, and delay responses are plotted relative to the sample and choice lever presses that they followed.</p

Properties of recorded action potentials.

<p>(A) Peak to trough action potential width vs. log firing rate for cells classified with each of the most commonly observed response types. (B) Tetrode recordings and (C) interspike interval (ISI) histogram from a neuron with narrow width (125 μs). (D) Tetrode recordings and (E) ISI histogram for a neuron with a wide width (344 μs). Calibration marks are 50 μV (vertical) and 200 μs (horizontal) in B and D. Red lines indicate 1 ms ISI (C, E).</p

Spatial heat maps (A to F) and peri-event time histograms (PETH) and raster plots (G to L) for neurons with spatially-restricted responses.

<p>Heat maps, oriented as in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0149019#pone.0149019.g005" target="_blank">Fig 5</a>, with activity in spikes/s indicated on the scale to the left of each plot and locations of base levers marked with small white arrows. PETHs show average spikes/s relative to different lever press responses. The 99% confidence intervals are indicated by the blue areas in each PETH. Raster plots are aligned with PETHs and show event markers for start (green), sample (blue), delay (red), and choice (yellow) responses for individual trials. Results are shown for delay (A, B, F, G, H, L), base lever press (C, I), reinforcement excitation (D, J), and reinforcement anticipation (E, K) responses.</p