Entorhinal circuits and memory functions

Several decades of research has convincingly indicated that the entorhinal-hippocampal system is a key component of circuits in the brain mediating episodic memory. Using rats as models, we have learned how memories may become encoded, stored and retrieve d. Focus has been on the hippocampus and the place-specific firing as the most conspicuous behavioural correlate of hippocampal principle cells. However, representation of space, and position in space, is only one component of episodic memory, and it has been reported that hippocampal principle cells also respond to non-spatial sensory inputs. Converging evidence from animal and human studies have pointed to the entorhinal cortex as the main structure to mediate the inflow of these two, functionally diffe rent sensory representations into the hippocampus. We have recently shown that the medial entorhinal cortex contains a metric representation of space, whereas others have shown that the lateral entorhinal cortex is the likely candidate structure to mediat e the non-spatial, cue or item-related sensory input. Since the foundation for a functional understanding of neural circuits is a detailed knowledge on how circuits are organized anatomically, the aim of the present project is to establish whether the pro cessing of different types of sensory inputs requires anatomically different networks, i.e. whether lateral and medial entorhinal cortex have different circuit properties, either with respect to intrinsic circuitry or with respect to how relevant sensory inputs interact with the intrinsic circuits. We will also analyse local circuits mediating integration between the two different sensory representations in lateral and medial entorhinal cortex. The results will ultimately be of importance for an increased understanding, and thus the development of diagnostic tools and treatment of devastating brain disorders such as alzheimer's dementia and epilepsy, both linked to initial damage in the entorhinal cortex.