PROJECT SUMMARY/ABSTRACT The projects proposed in this new grant address the properties of spatial coding in cortical regions. Representations of spatial location are important for a broad range of cognitive functions, including the planning of goal-directed navigation. This grant proposes specific experiments to test modeling predictions about the existence of egocentric representations of boundaries and coding of running speed relevant to the formation of allocentric spatial representations in cortical structures. Specific Aim #1: Recordings of the neural spiking activity in retrosplenial cortex and entorhinal cortex will test the hypothesis that cortical regions must code the position of environmental boundaries in egocentric coordinates. This prediction arose from models of the formation of allocentric representations of boundaries which require input from an egocentric, view-centered coding of environmental boundaries. Experiments will extend preliminary data from this lab showing egocentric coding of boundaries in retrosplenial cortex. Models show that egocentric boundary cells could be combined with head direction input to code allocentric boundary position, which can drive coding of spatial location. Further experiments will test the influence of environmental boundaries on spiking activity in the entorhinal cortex and retrospenial cortex, including testing the influence of manipulations of the shape of the environment, the insertion of new boundaries and different reward locations, recordings in darkness, and testing coexistence of egocentric coding with allocentric coding by head direction cells. This experimental testing of the predictions from models will provide an important link for building our understanding of the coding of space for cognitive processing. Specific Aim #2: Recordings of neural spiking activity in retrosplenial cortex and entorhinal cortex will test the complementary hypothesis that coding of running speed also plays a role in generation of representations of spatial location, and how the coding of running speed varies over different time courses and may depend on sensory input from boundaries. Experiments will include analysis of the coding of running speed at different spatial scales in entorhinal cortex and retrosplenial cortex ranging from one second to many minutes. The time course will also be analyzed in experiments exploring the change in running speed representations when barrier features are obscured by darkness. This aim also includes whole cell patch recording in slices to analyze the time course of intrinsic spiking activity relevant to the circuit dynamics for coding of speed and location. Finally, optogenetic inactivation of specific populations of neurons in medial septum will test how inputs regulate the coding of spatial location and speed by neurons in the medial entorhinal cortex. These experiments will contribute to our understanding of the dynamics of cortical circuits that underlie the formation of allocentric spatial representations important to many aspects of cortical cognitive processing, including the planning of goal-directed behavior.

PROJECT NARRATIVE This grant application proposes experiments focused on completing a missing link in models that connect the body-centered (egocentric) coding of sensory input about environmental boundaries and self-motion with world-centered (allocentric) coding of spatial boundaries, self-motion and spatial location. Preliminary data supporting this project shows egocentric coding of environmental boundaries and coding of running speed, and experiments will elucidate features of this coding that could contribute to world-centered coding that appears essential to brain mechanisms for guiding goal-directed behavior. Understanding these circuits could assist in understanding impairments of spatial navigation behavior associated with psychiatric and neurological diseases.