Synaptic organisation and behaviour-dependent activity of mGluR8a-innervated GABAergic trilaminar cells projecting from the hippocampus to the subiculum

Linda Katona,Abhilasha Joshi,Ryohei Tomioka,Kristina Wagner,Kathleen S Rockland,Thomas Klausberger,Jozsef Somogyi,Peter Somogyi,J David B Roberts,Katja Hartwich

doi:10.1007/s00429-020-02029-2

Abstract

In the hippocampal CA1 area, the GABAergic trilaminar cells have their axon distributed locally in three layers and also innervate the subiculum. Trilaminar cells have a high level of somato-dendritic muscarinic M2 acetylcholine receptor, lack somatostatin expression and their presynaptic inputs are enriched in mGluR8a. But the origin of their inputs and their behaviour-dependent activity remain to be characterised. Here we demonstrate that (1) GABAergic neurons with the molecular features of trilaminar cells are present in CA1 and CA3 in both rats and mice. (2) Trilaminar cells receive mGluR8a-enriched GABAergic inputs, e.g. from the medial septum, which are probably susceptible to hetero-synaptic modulation of neurotransmitter release by group III mGluRs. (3) An electron microscopic analysis identifies trilaminar cell output synapses with specialised postsynaptic densities and a strong bias towards interneurons as targets, including parvalbumin-expressing cells in the CA1 area. (4) Recordings in freely moving rats revealed the network state-dependent segregation of trilaminar cell activity, with reduced firing during movement, but substantial increase in activity with prolonged burst firing (> 200 Hz) during slow wave sleep. We predict that the behaviour-dependent temporal dynamics of trilaminar cell firing are regulated by their specialised inhibitory inputs. Trilaminar cells might support glutamatergic principal cells by disinhibition and mediate the binding of neuronal assemblies between the hippocampus and the subiculum via the transient inhibition of local interneurons.

Highlights

By performing high-resolution quantitative immunohistochemical analyses of M2/mGluR8a-labelled neuronal connections (Figs. 1, 2, 3, 4, 5), we have established the presence of molecularly identified trilaminar cells in the CA3 area in rat (Figs. 1b, d, f, 2a) and we investigated their distribution in mouse
We showed that GABAergic neurons with the molecular features of trilaminar cells are embedded into the hippocampal CA1 and CA3 neuronal network, in both the rat and the mouse, with their activity segregated by behavioural and network states
We established that this activity is regulated by inhibitory inputs, including those from the medial septum, which are susceptible to hetero-synaptic modulation of their neurotransmitter release mediated by group III mGluR8a and mGluR7a receptors

Summary

Introduction

The hippocampal formation contributes to episodic memory formation (Lorente de No 1934; Manns and Eichenbaum 2006; Squire et al 2004) served by a complex network of excitatory cortico-cortical associative and commissural pathways including those between the entorhinal cortex, the dentate gyrus, the hippocampal areas CA1–3 and the subiculum and projections to and from subcortical areas (Amaral and Witter 1989; Colom et al 2005; Ishizuka et al 1990; Kohara et al 2014; Ramon and Cajal 1893; Swanson and Cowan 1977; Wouterlood et al 1990).In addition to the complex network of glutamatergic pathways, an increasing number of long-range GABAergic projections have been reported, involving diverse neuronal types and synaptic mechanisms (Alonso and Köhler 1982; Basu et al 2016; Ceranik et al 1997; Christenson Wick et al 2019; Eyre and Bartos 2019; Ferraguti et al 2005; Francavilla et al 2018; Freund 1992; Freund and Meskenaite 1992; Fuentealba et al 2008; Jinno et al 2007; Katona et al 2017; Luo et al 2019; Melzer et al 2012; Miyashita and Rockland 2007; Ribak et al 1986; Sik et al 1995, 1994; Szőnyi et al 2019; Yamawaki et al 2019; Yuan et al 2017). In the hippocampal CA1, several distinct long-range projecting GABAergic neuron types have been identified coordinating neuronal activity of their targets in a behavioural‐ and rhythmic state‐dependent manner. Many of these express somatostatin (SST+) and have multi-area targets in both retrohippocampal areas, e.g. subiculum, and rostral areas, e.g. the medial septum (Christenson Wick et al 2019; Fuentealba et al 2008; Jinno et al 2007; Katona et al 2017; Miyashita and Rockland 2007). These SST+ neurons contribute to the dendritic inhibition of pyramidal cells (Jinno et al 2007; Katona et al 2017; Melzer et al 2012)

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Results

Conclusion