No abstract

The factors that control the spatial tuning of hippocampal neurons are incompletely understood, and there is no generally agreed upon definition of what constitutes a "place field". One factor that must be considered is the phenomenon of "phase precession". As a rat passes through the place field of a particular hippocampal neuron, its spikes shift to earlier phases of the theta rhythm. Except for the special cases discussed herein, the phase shift never exceeds 360 degrees. Moreover, under conditions in which place field sizes change dynamically, precession rate is tightly coupled with the place field size, suggesting that a single cycle of theta phase precession could be used to define unitary place field boundaries. Theta phase precession implies that the "cell assembly" of active hippocampal neurons changes systematically over the course of a single theta cycle. A given cell can exhibit more than one place field in a given environment, each field showing the same pattern of 360 degrees of phase precession. The existence of multiple fields implies that one cell can participate in multiple cell assemblies within the same environment. We show here that place fields, defined as a single cycle of phase precession, can overlap spatially, with the result that the cell fires with spikes clustered at two different phases over the theta cycles in which the fields overlap. Thus, the same neuron can participate in different cell assemblies within a single theta cycle.

Goal-directed behaviors require the consideration and expenditure of physical effort. The anterior cingulate cortex (ACC) appears to play an important role in evaluating effort and reward and in organizing goal-directed actions. Despite agreement regarding the involvement of the ACC in these processes, the way in which effort-, reward-, and motor-related information is registered by networks of ACC neurons is poorly understood. To contrast ACC responses to effort, reward, and motor behaviors, we trained rats on a reversal task in which the selected paths on a track determined the level of effort or reward. Effort was presented in the form of an obstacle that was climbed to obtain reward. We used single-unit recordings to identify neural correlates of effort- and reward-guided behaviors. During periods of outcome anticipation, 52% of recorded ACC neurons responded to the specific route taken to the reward while 21% responded prospectively to effort and 12% responded prospectively to reward. In addition, effort- and reward-selective neurons typically responded to the route, suggesting that these cells integrated motor-related activity with expectations of future outcomes. Furthermore, the activity of ACC neurons did not discriminate between choice and forced trials or respond to a more generalized measure of outcome value. Nearly all neural responses to effort and reward occurred after path selection and were restricted to discrete temporal/spatial stages of the task. Together, these findings support a role for the ACC in integrating route-specific actions, effort, and reward in the service of sustaining discrete movements through an effortful series of goal-directed actions.

The medial prefrontal cortex (mPFC) plays a critical role in the organization of goal-directed behaviors and in the learning of reinforcement contingencies. Given these observations, it was hypothesized that mPFC neurons may store associations between sequentially paired stimuli when both stimuli contribute to the prediction of reward. To test this hypothesis, neural-ensemble spiking activity was recorded as rats performed a paired-associate discrimination task. Rats were trained to associate sequentially presented stimuli with probabilistic reward. In one condition, both elements of the stimulus sequence provided information about reward delivery. In another condition, only the first stimulus contributed to the prediction. As hypothesized, stimulus-selective, prospective delay activity was observed during sequences in which both elements contributed to the prediction of reward. Unexpectedly, selective delay responses were associated with slight variations in head position and thus not necessarily generated by intrinsic mnemonic processes. Interestingly, the sensitivity of neurons to head position was greatest during intervals when reward delivery was certain. These results suggest that a significant portion of delay activity in the rat mPFC reflects task-relevant sensorimotor activity, possibly related to enhancing stimulus detection, rather than stimulus-stimulus associations. These observations agree with recent evidence that suggests that prefrontal neurons are particularly responsive during the performance of action sequences related to the acquisition of reward. These results also indicate that considerable attention must be given to the monitoring and analysis of sensorimotor variables during delay tasks because slight changes in position can produce activity in the mPFC that erroneously appears to be driven by intrinsic mechanisms.

Rewards influence responses to acute painful stimuli, but the relationship of chronic pain to hedonic or motivational aspects of reward is not well understood. Here, we independently evaluated hedonic qualities of sweet or bitter tastants as well as motivation to seek food reward in rats with experimental neuropathic pain induced by L5/6 spinal nerve ligation (SNL). Hedonic response was measured by implantation of intraoral catheters to allow passive delivery of liquid solutions and “liking/disliking” responses were scored according to a facial reactivity scale. SNL rats did not differ from controls in either “liking” or “disliking” reactions to intraoral sucrose or quinine, respectively, at post-surgery day 21, suggesting no differences in perceived hedonic value of sweet or bitter tastants. To assess possible motivational deficits during acute and chronic pain, we employed fixed- and progressive-ratio response paradigms of sucrose pellet presentation in rats with transient inflammatory or chronic neuropathic pain. Assessment of response acquisition and break points under the progressive ratio schedule revealed no differences between sham and SNL rats for up to 120 days post-injury. However, rats with inflammation showed decrements in lever pressing and break points on post-CFA days 1 and 2 that normalized by day 4, consistent with transient ongoing pain. Thus, while acute, ongoing inflammatory pain may transiently reduce reward motivation, we did not detect influences of chronic neuropathic pain on hedonic or motivational responses to food rewards. Adaptations that allow normal reward responding to food regardless of chronic pain may be of evolutionary benefit to promote survival.