# Functional and structural organization of medial entorhinal cortex layer VI

## TL;DR

The study reveals how the medial entorhinal cortex layer VI processes hippocampal signals and organizes them in parallel streams.

## Contribution

The paper identifies the topographic organization of hippocampal projections to MEC LVI and sparse connectivity within MEC deep layers.

## Key findings

- Hippocampal sharp wave-ripple complexes reliably propagate to MEC LVI excitatory neurons.
- Hippocampal projections to MEC LVI follow a parallel dorsoventral topography.
- Connectivity between MEC LVI and LV neurons is very sparse in both directions.

## Abstract

Deep layers (V/VI) of the entorhinal cortex transfer hippocampal neuronal activity to downstream neocortical networks. In addition, neurons in layer VI (LVI) of the medial entorhinal cortex (MEC) project back to all hippocampal subregions and contribute to spatial coding and memory. Their role in the processing of hippocampal output signals and their interaction with LV neurons is, however, unknown. We show that spontaneously occurring hippocampal sharp wave-ripple complexes reliably propagate from area CA1 to MEC LVI. Using anterograde tracing and in vitro optogenetics, we confirm direct hippocampal projections to LVI and show that these follow a parallel dorsoventral topography. Further investigation of the MEC deep layer network revealed very sparse excitatory connections between LVI and LVb or LVI and LVa neurons in both directions. Together, our results establish organizational principles for the hippocampal-MEC LVI output circuit and suggest largely parallel signal processing through different cellular subpopulations in MEC deep layers.

•Hippocampal SPW-R reliably propagate to MEC LVI excitatory neurons•Hippocampal projections to MEC LVI are topographically organized•Connectivity between MEC LVI and LVa or LVb excitatory neurons is very sparse•Signals in MEC deep layers are processed in largely parallel streams of activity

Hippocampal SPW-R reliably propagate to MEC LVI excitatory neurons

Hippocampal projections to MEC LVI are topographically organized

Connectivity between MEC LVI and LVa or LVb excitatory neurons is very sparse

Signals in MEC deep layers are processed in largely parallel streams of activity

Natural sciences; Biological sciences; Neuroscience; Systems neuroscience