Rhythmic oscillations in the midbrain dopaminergic nuclei in mice.

Introduction: Dopamine release in the forebrain by midbrain ventral tegmental nucleus (VTA) and substantia nigra pars compacta (SNc) neurons is implicated in reward processing, goal-directed learning, and decision-making. Rhythmic oscillations of neural excitability underlie coordination of network processing, and have been reported in these dopaminergic nuclei at several frequency bands. This paper provides a comparative characterization of several frequencies of oscillations of local field potential and single unit activity, highlighting some behavioral correlates. Methods: We recorded from optogenetically identified dopaminergic sites in four mice training in operant olfactory and visual discrimination tasks. Results: Rayleigh and Pairwise Phase Consistency (PPC) analyses revealed some VTA/SNc neurons phase-locked to each frequency range, with fast spiking interneurons (FSIs) prevalent at 1-2.5 Hz (slow) and 4 Hz bands, and dopaminergic neurons predominant in the theta band. More FSIs than dopaminergic neurons were phase-locked in the slow and 4 Hz bands during many task events. The highest incidence of phase-locking in neurons was in the slow and 4 Hz bands, and occurred during the delay between the operant choice and trial outcome (reward or punishment) signals. Discussion: These data provide a basis for further examination of rhythmic coordination of activity of dopaminergic nuclei with other brain structures, and its impact for adaptive behavior.

Activation of prefrontal cortex and striatal regions in rats after shifting between rules in a T-maze.

Prefrontal cortical and striatal areas have been identified by inactivation or lesion studies to be required for behavioral flexibility, including selecting and processing of different types of information. In order to identify these networks activated selectively during the acquisition of new reward contingency rules, rats were trained to discriminate orientations of bars presented in pseudorandom sequence on two video monitors positioned behind the goal sites on a T-maze with return arms. A second group already trained in the visual discrimination task learned to alternate left and right goal arm visits in the same maze while ignoring the visual cues still being presented. In each experimental group, once the rats reached criterion performance, the brains were prepared after a 90-min delay for later processing for c-fos immunohistochemistry. While both groups extinguished a prior strategy and acquired a new rule, they differed by the identity of the strategies and previous learning experience. Among the 28 forebrain areas examined, there were significant increases in the relative density of c-fos immunoreactive cell bodies after learning the second rule in the prefrontal cortex cingulate, the prelimbic and infralimbic areas, the dorsomedial striatum and the core of the nucleus accumbens, the ventral subiculum, and the central nucleus of the amygdala. These largely correspond to structures previously identified in inactivation studies, and their neurons fire synchronously during learning and strategy shifts. The data suggest that this dynamic network may underlie reward-based selection for action-a type of cognitive flexibility.

Distributed cell assemblies spanning prefrontal cortex and striatum.

Highly synchronous neuronal assembly activity is deemed essential for cognitive brain function. In theory, such synchrony could coordinate multiple brain areas performing complementary processes. However, cell assemblies have been observed only in single structures, typically cortical areas, and little is known about their synchrony with downstream subcortical structures, such as the striatum. Here, we demonstrate distributed cell assemblies activated at high synchrony (∼10 ms) spanning prefrontal cortex and striatum. In addition to including neurons at different brain hierarchical levels, surprisingly, they synchronized functionally distinct limbic and associative sub-regions. These assembly activations occurred when members shifted their firing phase relative to ongoing 4 Hz and theta rhythms, in association with high gamma oscillations. This suggests that these rhythms could mediate the emergence of cross-structural assemblies. To test for the role of assemblies in behavior, we trained the rats to perform a task requiring cognitive flexibility, alternating between two different rules in a T-maze. Overall, assembly activations were correlated with task-relevant parameters, including impending choice, reward, rule, or rule order. Moreover, these behavioral correlates were more robustly expressed by assemblies than by their individual member neurons. Finally, to verify whether assemblies can be endogenously generated, we found that they were indeed spontaneously reactivated during sleep and quiet immobility. Thus, cell assemblies are a more general coding mechanism than previously envisioned, linking distributed neocortical and subcortical areas at high synchrony.