Distinct synaptic properties of perisomatic inhibitory cell types and their different modulation by cholinergic receptor activation in the CA3 region of the mouse hippocampus.

Gergely G Szabó,Tamás F Freund,Norbert Hájos,Noémi Holderith,Attila I Gulyás

doi:10.1111/j.1460-9568.2010.07292.x

Abstract

Perisomatic inhibition originates from three types of GABAergic interneurons in cortical structures, including parvalbumin-containing fast-spiking basket cells (FSBCs) and axo-axonic cells (AACs), as well as cholecystokinin-expressing regular-spiking basket cells (RSBCs). These interneurons may have significant impact in various cognitive processes, and are subjects of cholinergic modulation. However, it is largely unknown how cholinergic receptor activation modulates the function of perisomatic inhibitory cells. Therefore, we performed paired recordings from anatomically identified perisomatic interneurons and pyramidal cells in the CA3 region of the mouse hippocampus. We determined the basic properties of unitary inhibitory postsynaptic currents (uIPSCs) and found that they differed among cell types, e.g. GABA released from axon endings of AACs evoked uIPSCs with the largest amplitude and with the longest decay measured at room temperature. RSBCs could also release GABA asynchronously, the magnitude of the release increasing with the discharge frequency of the presynaptic interneuron. Cholinergic receptor activation by carbachol significantly decreased the uIPSC amplitude in all three types of cell pairs, but to different extents. M2-type muscarinic receptors were responsible for the reduction in uIPSC amplitudes in FSBC– and AAC–pyramidal cell pairs, while an antagonist of CB1 cannabinoid receptors recovered the suppression in RSBC–pyramidal cell pairs. In addition, carbachol suppressed or even eliminated the short-term depression of uIPSCs in FSBC– and AAC–pyramidal cell pairs in a frequency-dependent manner. These findings suggest that not only are the basic synaptic properties of perisomatic inhibitory cells distinct, but acetylcholine can differentially control the impact of perisomatic inhibition from different sources.

Highlights

In cortical structures only every fifth neuron is GABAergic (Somogyi et al, 1998), these neurons significantly influence information processing in neuronal networks (Miles et al, 1996; Pouille & Scanziani, 2004)
In this study we showed that axo-axonic cell (AAC) can be unequivocally distinguished from basket cells at the light-microscopic level using double immunofluorescent staining to visualize biocytin-filled axon collaterals and axon initial segment (AIS) with ankyrin-G
Paired recordings obtained from perisomatic inhibitory cells and pyramidal neurons revealed that AACs produced unitary IPSC (uIPSC) with the largest amplitudes and with the longest decays, probably due to the spillover of GABA between release sites under our recording conditions

Summary

Introduction

In cortical structures only every fifth neuron is GABAergic (Somogyi et al, 1998), these neurons significantly influence information processing in neuronal networks (Miles et al, 1996; Pouille & Scanziani, 2004). Cortical GABAergic cells with local axonal projections can be divided into two major categories: cells innervating predominantly either the perisomatic membranes or the dendrites of principal neurons (Buhl et al, 1994; Miles et al, 1996); this study does not address the latter category. The perisomatic region is defined as the domain of the plasma membrane which includes the proximal dendrites, the cell body and the axon initial segment (AIS; Freund & Buzsaki, 1996). This region is targeted by three types of inhibitory neurons in cortical areas, namely by the parvalbumin (PV)-expressing fast-spiking basket cells (FSBCs) and. The basket cells innervate the somata and proximal dendrites (Blackstad & Flood, 1963) whereas the AACs target the AISs of pyramidal neurons (Somogyi, 1977)

Methods

Results

Conclusion