Contextual representations serve to guide many aspects of behavior and influence the way stimuli or actions are encoded and interpreted. The medial prefrontal cortex (mPFC), including the anterior cingulate subregion, has been implicated in contextual encoding, yet the nature of contextual representations formed by the mPFC is unclear. Using multiple single-unit tetrode recordings in rats, we found that different activity patterns emerged in mPFC ensembles when animals moved between different environmental contexts. These differences in activity patterns were significantly larger than those observed for hippocampal ensembles. Whereas ≈11% of mPFC cells consistently preferred one environment over the other across multiple exposures to the same environments, optimal decoding (prediction) of the environmental setting occurred when the activity of up to ≈50% of all mPFC neurons was taken into account. On the other hand, population activity patterns were not identical upon repeated exposures to the very same environment. This was partly because the state of mPFC ensembles seemed to systematically shift with time, such that we could sometimes predict the change in ensemble state upon later reentry into one environment according to linear extrapolation from the time-dependent shifts observed during the first exposure. We also observed that many strongly action-selective mPFC neurons exhibited a significant degree of context-dependent modulation. These results highlight potential differences in contextual encoding schemes by the mPFC and hippocampus and suggest that the mPFC forms rich contextual representations that take into account not only sensory cues but also actions and time.electrophysiological recordings | population analysis | temporal encoding M any aspects of behavior are contextually dependent. Contexts can be abstract, as in the case of human language, or can be more concrete and be defined by the constellation of spatial and sensory stimuli surrounding an individual. Contextual representations can form quickly and tend to remain stable despite local variations in perspective (1). Context can also help to inform the subject about potential changes in the meaning of stimuli and actions. The medial prefrontal cortex (mPFC) is involved in various forms of cognition that depend on spatial and contextual information, including context-based cognitive tasks (2-4), contextual fear conditioning (5), and context-induced drug relapse (6-8), and is believed to be an important node in the "context" network (1, 9-12). These functions likely depend on reciprocal interactions with the hippocampus (13, 14), an area that has a well-established role in spatial and contextual processing (15)(16)(17)(18)(19)(20). Through the connection from the CA1 region, the hippocampus has multiple profound effects on mPFC neurons (21-28), and it has been proposed that during spatial navigation the mPFC may work in concert with the hippocampus to encode goal locations and aid in route planning (29,30). However, the spatial representations ...

Cognitive control often requires suppression of prepotent stimulus-driven responses in favor of less potent alternatives. Suppression of prepotent saccades has been shown to require proactive inhibition in the frontoparietal saccade network. Electrophysiological evidence in macaque monkeys has revealed neural correlates of such inhibition in this network; however, the interlaminar instantiation of inhibitory processes remains poorly understood because these areas lie deep within sulci in macaques, rendering them inaccessible to laminar recordings. Here, we addressed this gap by exploiting the mostly lissencephalic cortex of the common marmoset (Callithrix jacchus). We inserted linear electrode arrays into areas 8Ad-the putative marmoset frontal eye field-and the lateral intraparietal area of two male marmosets and recorded neural activity during performance of a task comprised of alternating blocks of trials requiring a saccade either toward a large, high-luminance stimulus or the inhibition of this prepotent response in favor of a saccade toward a small, low-luminance stimulus. We observed prominent task-dependent activity in both alpha/gamma bands of the LFP and discharge rates of single neurons in area 8Ad during a prestimulus task epoch in which the animals had been instructed which of these two tasks to perform but before peripheral stimulus onset. These data are consistent with a model in which rhythmic alpha-band activity in deeper layers inhibits spiking in upper layers to support proactive inhibitory saccade control.Failures to inhibit automatic saccadic responses are a hallmark of many neuropsychiatric disorders, but how this process is implemented across the cortical layers in the frontoparietal saccade network remains unknown because many of the areas are inaccessible to laminar recordings in macaques. Here, we investigated laminar neural activity in marmoset monkeys, which have a smooth cortex. Monkeys were required either to generate or inhibit a prepotent saccade response. In area 8Ad, the putative frontal eye field in marmosets, rhythmic alpha-band activity (9 -14 Hz) was higher in deeper layers and spiking activity was lower in upper layers when the animals were instructed to suppress a saccade toward a peripheral stimulus. Reduced alpha power during task preparation may be the underlying common neural basis of a saccade suppression deficit.

When performing sequences of actions, we constantly keep track of our current position in the sequence relative to the overall goal. The present study searched for neural representations of sequence progression in corticostriatal circuits. Neurons within the anterior cingulate cortex (ACC) and its target region in the dorsal striatum (DS) were recorded from simultaneously as rats performed different sequences of lever presses. We analyzed the responses of the neurons to presses occurring in the "first," "second," or "third" serial position regardless of the particular sequence or physical levers. Principal component analysis revealed that the main source of firing rate variance in the ACC was a smooth ramp-like change as the animal progressed through the sequence toward the reward. No such smooth-ramping activity was observed in DS ensembles as firing tended to be tightly linked to each action. In the ACC, the progression in firing was observed only for correct choices and not errors, whereas in the DS, firing associated with each action in a sequence was similar regardless of whether the action was correct or not. Therefore, different forms of a signal exist within corticostriatal circuits that evolve across a sequence of actions, with DS ensembles tracking every action and ACC ensembles tracking actual progress toward the goal.

The frontal cortex has been implicated in a number of cognitive and motivational processes, but understanding how individual neurons contribute to these processes is particularly challenging as they respond to a broad array of events (multiplexing) in a manner that can be dynamically modulated by the task context, i.e., adaptive coding (Duncan, 2001). Fundamental questions remain, such as how the flexibility gained through these mechanisms is balanced by the need for consistency and how the ensembles of neurons are coherently shaped by task demands. In the present study, ensembles of medial frontal cortex neurons were recorded from rats trained to perform three different operant actions either in two different sequences or two different physical environments. Single neurons exhibited diverse mixtures of responsivity to each of the three actions and these mixtures were abruptly altered by context/sequence switches. Remarkably, the overall responsivity of the population remained highly consistent both within and between context/sequences because the gains versus losses were tightly balanced across neurons and across the three actions. These data are consistent with a reallocation mixture model in which individual neurons express unique mixtures of selectivity for different actions that become reallocated as task conditions change. However, because the allocations and reallocations are so well balanced across neurons, the population maintains a low but highly consistent response to all actions. The frontal cortex may therefore balance consistency with flexibility by having ensembles respond in a fixed way to task-relevant actions while abruptly reconfiguring single neurons to encode "actions in context."

The function of a given brain region is often defined by the coding properties of its individual neurons, yet how this information is combined at the ensemble level is an equally important consideration. In the present study, multiple neurons from the anterior cingulate cortex (ACC) and the dorsal striatum (DS) were recorded simultaneously as rats performed different sequences of the same three actions. Sequence and lever decoding was remarkably similar on a per-neuron basis in the two regions. At the ensemble level, sequence-specific representations in the DS appeared synchronously but transiently along with the representation of lever location, while these two streams of information appeared independently and asynchronously in the ACC. As a result the ACC achieved superior ensemble decoding accuracy overall. Thus, the manner in which information was combined across neurons in an ensemble determined the functional separation of the ACC and DS on this task.