The role of rat medial prefrontal cortex in spatial working memory

The prefrontal cortex has long been associated with executive function. Lesion studies have shown that this region is critical for representing information in the absence of sensory stimulation and for the planning and execution of actions in pursuit of future goals. While numerous studies in nonhuman primates have reported neurons in medial and dorsolateral prefrontal cortex that can sustain spatially selective firing over delays, far fewer studies have examined this question at the single neuron level in rodents. The experiments in this thesis aim to test the hypothesis that rat medial prefrontal cortex is critical for the successful performance of a working memory task---delayed spatial alternation. An operant version of this task was developed that was suitable for neurophysiological recordings. To address whether medial prefrontal cortex was critical for task performance, rats were implanted with cannulae in this region and muscimol was infused to locally inactivate neurons. Rats with inactivated medial prefrontal cortex were impaired in the task. This led to the hypothesis that neurons within this region must encode information about on-going task-related behaviors. Recordings from rats performing in delayed spatial alternation tasks revealed neurons with elevated delay period firing. Neurons with spatially selective firing around the spatial response and during the delay period were also observed. Finally, since the prefrontal cortex is involved in many processes that lead to goal acquisition, neurons were examined for non-spatial firing patterns. Some of the neurons with elevated firing throughout the delay did not show spatial selectivity. These neurons were considered to be phase-selective neurons that were modulated by the delay/reward epoch. Other neurons fired differentially based on correct versus error responses. These data support a role for the rat medial prefrontal cortex in mnemonic and non-mnemonic executive functions during the delay period of working memory tasks.