The hippocampus (HPC), medial entorhinal cortex (MEC), and retrosplenial cortex (RSC) are strongly implicated in memory, and atrophy of all three structures serves as an early indicator of Alzheimer's disease. In parallel to memory processes, these structures are important for spatial cognition and neurons within these regions exhibit spatially-specific firing. HPC place cells fire when an animal occupies an explicit location in the environment relative to distal visual landmarks. MEC neurons encode multiple forms of spatial information, including grid fields, wherein a single neuron is active at multiple, equidistant locations that span the entire environment and form a periodic grid. Critically, dysfunction of MEC spatial patterning disrupts sequential encoding in the HPC which is thought to underlie episodic memory. Robust MEC spatially-related firing is known to require visual information which is likely routed to the region via RSC. RSC forms a strong excitatory projection into the region, and like MEC, firing of RSC neurons can be rhythmic and exhibit spatial periodicity. Further, individual RSC neurons encode sensory, motor, and spatial variables that are known to modulate MEC activation. Although it is known that RSC is part of the visual processing network, little is known as to how RSC spatial representations are influenced by the arrangement of distal visual cues or how visually-related RSC activation in turn influences MEC activation. Given the functional and anatomical relationship between RSC and MEC, it is pertinent to explore their connectivity and joint neurophysiological dynamics at this time. This proposal seeks to further our understanding of systems interactions between MEC and RSC in spatial encoding. The proposed experiments will assay the influence of visual information in RSC and MEC spatial representations through the implementation of visual cue manipulations that expand or compress the relative angle between visual landmarks while rats perform a visually-guided navigation paradigm. Additionally, the proposed experiments will utilize optogenetics to specifically inhibit RSC projections into MEC to test hypotheses that RSC input is required for MEC visual sensitivity. Data collected in these experiments will be utilized to test computational modeling predictions about distortions to position estimation and MEC spatial representations following shifts to the known locations of familiar distal cues.
The proposed research will examine interactions between retrosplenial cortex and medial entorhinal cortex during visually-guided navigation. Further, optogenetic methods will be utilized to inhibit retrosplenial inputs into medial entorhinal cortex. Disruption of this circuit may underlie the learning, memory, and navigation impairments found in rats and humans following atrophy of these regions in disease pathology.
