Examining the Roles of Thalamocortical and Frontoparietal Circuitry for Working Memory in the Rat

Abstract

Working memory (WM) is the cognitive capacity for short-term maintenance and manipulation of stimuli and goals for the purpose of guiding behaviour. Research in primates has indicated that WM relies on a large network including the prefrontal cortex, various posterior cortical areas, and subcortical nuclei. However, the circuit mapping of WM in rodents is incomplete as it pertains to the specific involvement of thalamocortical and frontoparietal circuitry across WM tasks. In this dissertation, I present the findings of three sets of experiments using two different rodent WM tasks: The odour span task (OST), an incrementing delayed non-matching-to-sample task using odours, and; the Trial-Unique Non-matching-to-Location (TUNL) task, a touchscreen-based visuospatial delayed non-matching-to-sample task. 1) I found evidence that the OST relies on a thalamocortical circuit connecting the medial prefrontal cortex (mPFC) and the mediodorsal thalamus (mdThal). Moreover, the mPFC and mdThal played dissociable roles in the foraging element of the OST, with mdThal inactivation causing a dramatic reduction in exploratory motor activity. 2) I examined the role of the PPC in the OST and found that it is not necessary for OST performance. 3) I found that the PPC is critical for TUNL, confirming that the rodent PPC plays an essential role in visuospatial WM. Additionally, I found that TUNL is independent of NMDA signalling in the PPC and instead depends only on AMPA/Kainate receptors in contrast to previous research showing an important role for NMDA receptors in WM. Overall, the results indicate that thalamocortical and frontoparietal pathways are differentially involved across WM tasks, with frontoparietal circuitry being more sensory modality-specific than thalamocortical circuitry.