Prefrontal-thalamo-hippocampal circuit contributions to spatial working memory

Griffin, Amy L.A growing body of evidence suggests that different types of learning and memory processes are distributed across specialized neural circuits consisting of two or more anatomically- and functionally-connected brain areas. One such neural circuit consists of the dorsal hippocampus (dHC) and the medial prefrontal cortex (mPFC). This circuit is thought to be critically important for spatial working memory (the ability to flexibly maintain and use trial-specific spatial information within a testing session). dHC-mPFC interactions have been shown to correlate with spatial working memory-guided task performance in rodents; however, there are no direct anatomical connections between the dHC and mPFC. The reuniens and rhomboid (RE/Rh) nuclei of the ventral midline thalamus are bi-directionally connected with the infralimbic, prelimbic, and anterior cingulate sub-regions of the mPFC, as well as the CA1 subfield of dHC. The efferent and afferent connections of the RE/Rh suggest that these thalamic nuclei may support working memory by modulating interactions between the dHC and mPFC. This prediction was directly tested by simultaneously recording single units and local field potentials (LFPs) from CA1 of the dHC and the mPFC while rats performed a working memory-dependent delayed spatial alternation (DA) task in a T-maze. The DA task is dependent on the functional integrity of RE/Rh (Experiment 1), and increased hippocampal-prefrontal synchrony is seen during good performance of the DA task, as compared to a control task (CD; Experiment 2). Prior to the recording session, RE/Rh were functionally inactivated by an intracranial infusion of the GABAA receptor agonist muscimol. Our results show that RE/Rh inactivation caused severe performance impairments that were accompanied by decreases in hippocampal-prefrontal synchrony on the maze (Experiment 3). These results provide a novel characterization of the mechanisms underlying memory-guided decision making by directly examining the relationship between thalamic gating of cortico-limbic interactions and spatial working memory performance.University of Delaware, Department of Psychological and Brain SciencesPh.D