Sources of spatial tuning in the dorsal subiculum

Abstract

Spatial navigation is an essential behavior for all moving life-forms. A main mammalian brain structure implicated in this process is the hippocampal formation. Neuronal firing patterns in this brain region are remarkably correlated to various aspects of the animal’s location and navigation. The subiculum is a primary output structure of hippocampal information processing, providing output to various cortical and subcortical areas. With this crucial position within the hippocampal formation, the primary role of the subiculum is to integrate, compress and then distribute hippocampally-processed information to the whole brain. Two major inputs to the subiculum arise from the CA1 region and the entorhinal cortex. This study investigates the individual roles of these two input streams in generating spatially correlated firing of subicular neurons. <br /> In vivo whole cell patch clamp recordings in mice running freely on a circular track revealed that dorsal subicular neurons receive spatially tuned input. Additionally, channelrodopsin assisted circuit mapping showed, that the two major input streams target specific regions in the dendritic tree of dorsal subicular neurons. Specifically, CA1 input is located more proximal, while EC input forms synapses in the distal part of the dendritic tree of dorsal subicular neurons. Finally, individual contributions of both input streams on the spatial tuning of dorsal subicular neurons were investigated using two-photon calcium imaging in mice running on a linear treadmill. Chemogenetic inactivation of either CA1 or entorhinal cortex inputs via viral transduction of the inhibitory DREADD and local application of CNO by a small hole in the imaging window, revealed district contributions of both inputs paths: CA1 inputs are necessary for the place and velocity tuning, while EC inputs are only necessary for the place tuning of dorsal subicular neurons.<br /> Taken together my experiments demonstrate that (I) subicular neurons receive spatial and velocity tuned input (II), that subicular neurons maintain a functional input segregation between CA1 and entorhinal cortex synapses and (III) that both input streams play differential roles in shaping the spatial tunings of subicular neurons with respect to place and movement speed. This study emphasizes the need to differentiate between the information that one brain region could potentially receive from other brain regions and the information that is actually used by the postsynaptic neuron during their input-output transformation.