CRCNS: US-Israel - The egocentric-allocentric transformation of the cognitive map

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Animals have the striking ability to know where they are, and to plan where to go and how to get there. These abilities are likely based on a cognitive map, the brain’s internal representation of space. For 50 years we have known that hippocampal place cells are a component of the cognitive map, responding when an animal is in specific locations. We also know about other components of the map – e.g., grid cells, head-direction cells, and border cells. But we do not understand how the responses of such cells are generated from sensory experience. One puzzle is that sensory inputs are “egocentric” (centered and oriented in relation to the individual), whereas the cognitive map is “allocentric” (centered and oriented in relation to an absolute reference frame in the world). This raises a key question: how does the brain transform egocentric reference frames into allocentric ones to guide behavior? We focus on the part of the cognitive map representing boundaries. Boundaries are experienced egocentrically by animals, but in the medial entorhinal cortex (MEC) and the subicular complex, borders are represented by allocentric boundary cells (ABCs). If ABCs can be generated from egocentric responses in upstream areas, their allocentricity could be propagated to the rest of the cognitive map via synaptic interactions. Recent work shows that the postrhinal cortex (POR), a principal area projecting to the MEC, contains cells with egocentric responses that may encode boundaries. In Aim 1, we propose that these are Egocentric Boundary Cells (EBCs) that efficiently encode orientations and distances to boundary segments, as subjectively experienced during navigation. We will test this idea by recording egocentric POR responses in environments of varying complexity, while testing the tuning of responses to spatial boundaries, and comparing to predictions of efficient coding theory. In Aim 2 we further propose a mechanism whereby EBC responses in POR are conjunctively and hierarchically combined with head-direction responses through Hebbian plasticity in the MEC, to produce ABC responses. We will test this mechanism through environmental manipulations and confusion experiments combined with neural recordings, for which we will have predictions from theoretical models. We will also perform anatomical studies and inactivation experiments to test how components of the network connect, and how functionality is modified when some parts of the network are inactivated. Our approach will achieve a significant milestone, uncovering circuits, brain areas, and mechanisms connecting sensory experience to the generation of the brain’s cognitive map, thus informing clinical approaches to deficits in navigation and episodicmemory. RELEVANCE (See instructions): This work will develop a systems-level understanding of circuits across brain areas that underpin spatial cognition, our ability to know where we are and to plan where we go. We must understand how the brain solves such spatial problems to treat impairment of the ability to navigate, a common deficit in patients with early stage dementia or temporal lobe trauma. As spatial cognition is closely tied to episodic memory and abstract navigation, this work will also help to guide clinical approaches to impairment of these capacities.