Cognition and memory result from communication between specific populations of neurons in our brains. In the medial entorhinal cortex (MEC), representations of location that are crucial for spatial cognition and memory are generated by neurons called grid cells. The rate at which these neurons fire action potentials can be decoded into fields that for
m a hexagonal grid spanning the environment. In addition to the action potential rate, the information about spatial location is also encoded by the timing of action potentials relative to the phase of local theta frequency oscillations in network activity. The action potential rate and timing codes require synaptic input from a subcortical structure called the medial septum and diagonal band complex (MS-DB). Yet, we know very little about how projections from the MS-DB influence neurons in the MEC. I propose to establish principles whereby a major subtype of MS-DB neurons, which express the inhibitory neurotransmitter GABA, influence activity of neurons in the MEC. I will combine optogenetic tools, to selectively activate GABAergic inputs from the MS-DB, with state of the art in vitro and in vivo electrophysiological recordings to identify and characterize their targets in the MEC. My approach will include the use of a new multi electrode array recording method that I will transfer to Europe, which will allow me to identify targets of MS-DB GABAergic neurons by simultaneously sampling large populations of neurons in the MEC. During my PhD I was the first to publish this method, which is currently not utilized in Europe. The proposal will advance the understanding of cellular and circuit mechanisms for spatial cognition and memory. It will also contribute to identification of design principles for biologically based computational devices for navigational control systems and new approaches to treating disorders such as Alzheimer’s, epilepsy and schizophrenia in which the MEC is implicated.
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