Dissertation Defense - Ellen KW Brennan
“Functional Microcircuitry of the Granular Retrosplenial Cortex”
Dr. Omar Ahmed, Chair
The granular retrosplenial cortex (RSG) is essential for successful spatial navigation and memory, but the cell types and cellular computations underlying these functions remain poorly understood. Using a multifaceted approach combining whole-cell patch clamp recordings, imaging, pharmacological interventions, and computational models, this dissertation provides a comprehensive investigation of the cells, circuits, and computations employed by the RSG to support navigational functions. First, we identify a unique, hyperexcitable pyramidal cell type localized to the superficial layers of RSG, which we name the low-rheobase (LR) neuron. We show that the intrinsic properties of LR cells make them ideally suited to encode persistent spatial information over long durations. Next, we show that these LR neurons are strongly and preferentially targeted by directional and spatial inputs from the anterior thalamus and dorsal subiculum due to the precise anatomical overlap of LR dendrites and thalamic/subicular afferents. In contrast, neighboring regular-spiking (RS) cells are targeted by mostly non-spatial claustral and anterior cingulate inputs, establishing parallel RSG circuits that encode spatial versus non-spatial signals. Using computational modeling, we show that LR cells can conjunctively encode head direction and speed as a result of the uniquely depressing nature of their anterior thalamic synaptic inputs, providing a robust mechanism for the conjunctive encoding of spatial orientation information in the RSG. Finally, we show that LR neuron activity is not directly modulated by acetylcholine, suggesting that LR spatial coding is consistent across behavioral states and independent of cholinergic tone. Taken together, the results presented in this dissertation show that LR neurons are critical for the encoding of spatial orientation information in the RSG and provide specific circuit and synaptic mechanisms underlying retrosplenial contributions to successful navigational control.