Shared rhythmic subcortical GABAergic input to the entorhinal cortex and presubiculum.

Tim James Viney,Minas Salib,Gunes Unal,Abhilasha Joshi,Naomi Berry,Peter Somogyi

doi:10.7554/elife.34395

Abstract

Rhythmic theta frequency (~5-12 Hz) oscillations coordinate neuronal synchrony and higher frequency oscillations across the cortex. Spatial navigation and context-dependent episodic memories are represented in several interconnected regions including the hippocampal and entorhinal cortices, but the cellular mechanisms for their dynamic coupling remain to be defined. Using monosynaptically-restricted retrograde viral tracing in mice, we identified a subcortical GABAergic input from the medial septum that terminated in the entorhinal cortex, with collaterals innervating the dorsal presubiculum. Extracellularly recording and labeling GABAergic entorhinal-projecting neurons in awake behaving mice show that these subcortical neurons, named orchid cells, fire in long rhythmic bursts during immobility and locomotion. Orchid cells discharge near the peak of hippocampal and entorhinal theta oscillations, couple to entorhinal gamma oscillations, and target subpopulations of extra-hippocampal GABAergic interneurons. Thus, orchid cells are a specialized source of rhythmic subcortical GABAergic modulation of 'upstream' and 'downstream' cortico-cortical circuits involved in mnemonic functions.

Highlights

When an animal explores an environment, hippocampal ‘place cells’ represent different locations forming a spatial map and discharging rhythmic bursts of action potentials in temporal sequences (O’Keefe and Recce, 1993)
Different GABAergic cell types target distinct subcellular domains of principal cells, each cell type preferentially firing during specific phases of network oscillations, which together contribute to a temporal redistribution of inhibition from the axon initial segment, to the soma, and all the way to the distal dendrites of principal cells (Somogyi et al, 2014; Varga et al, 2012)
When we tested for rhythmic burst firing during CA1d large amplitude irregular activity (LIA) (

Summary

Introduction

When an animal explores an environment, hippocampal ‘place cells’ represent different locations forming a spatial map and discharging rhythmic bursts of action potentials in temporal sequences (O’Keefe and Recce, 1993). Coordination of neuronal assemblies, such as place cell sequences, is controlled by local GABAergic neurons setting temporal windows of differential excitability and synchronizing neuronal activity over various time scales reflected by underlying network oscillations (Cobb et al, 1995; Ylinen et al, 1995). Such temporal coordination includes theta oscillations (~5–12 Hz) most prominent during movement and REM sleep (Kramis et al, 1975), gamma oscillations (~30–120 Hz), which are phaseamplitude coupled to theta (Colgin et al, 2009; Lasztoczi and Klausberger, 2016; Schomburg et al, 2014; Soltesz and Deschenes, 1993) and hippocampal sharp-wave associated ripple oscillations (SWRs, 130–230 Hz) mainly occurring during slow wave sleep, awake immobility and consummatory behavior (Buzsaki, 1986). Given the diversity of rhythmic firing patterns these cortical GABAergic cell types, which neurons and circuits support their temporal coordination?

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