GABAergic Input Affects Intracellular Calcium Levels in Developing Granule Cells of Adult Rat Hippocampus.

Davide Lattanzi,Michael Di Palma,Riccardo Cuppini,Patrizia Ambrogini

doi:10.3390/ijms21051715

Davide Lattanzi, Michael Di Palma + Show 2 more

Open Access

https://doi.org/10.3390/ijms21051715

Copy DOI

Abstract

In the dentate gyrus (DG) of the mammalian hippocampus, granule neurons are generated from neural stem cells (NSCs) throughout the life span and are integrated into the hippocampal network. Adult DG neurogenesis is regulated by multiple intrinsic and extrinsic factors that control NSC proliferation, maintenance, and differentiation into mature neurons. γ-Aminobutyric acid (GABA), released by local interneurons, regulates the development of neurons born in adulthood by activating extrasynaptic and synaptic GABAA receptors. In the present work, patch-clamp and calcium imaging techniques were used to record very immature granule cells of adult rat dentate gyrus for investigating the actual role of GABAA receptor activation in intracellular calcium level regulation at an early stage of maturation. Our findings highlight a novel molecular and electrophysiological mechanism, involving calcium-activated potassium channels (BK) and T-type voltage-dependent calcium channels, through which GABA fine-tunes intracellular calcium homeostasis in rat adult-born granule neurons early during their maturation. This mechanism might be instrumental in promoting newborn cell survival.

Highlights

The hippocampus dentate gyrus (DG) subgranular zone (SGZ) represents one of the neurogenic niches where radial glia-like neural stem cells (NSCs) continuously generate new neurons throughout adulthood
Spontaneous membrane potential oscillations observed in very immature neurons of adult rat dentate gyrus were related to intracellular calcium level alterations and their modulation by GABA activity was investigated
The main results we found were the following: (i) resting membrane potential oscillations were able to elicite calcium entry into the cell, increasing intracellular calcium concentration; (ii) BK channels and T-Type VDCCs were involved in generating membrane potential oscillations; (iii) GABAAR activation was able to decrease intracellular calcium level, probably shunting membrane currents and dampening resting membrane potential oscillations

Summary

Introduction

The hippocampus dentate gyrus (DG) subgranular zone (SGZ) represents one of the neurogenic niches where radial glia-like neural stem cells (NSCs) continuously generate new neurons throughout adulthood. This process, known as adult neurogenesis, can be outlined as the stepwise progression of NSCs into progenitor cells, neuroblast fate specification, neuronal differentiation in dentate granule cells (GCs), survival, and their synaptic integration into the existing circuitry to participate in the hippocampal function [1,2]. Its functions are first mediated by tonic activation of extrasynaptic ionotropic GABAA receptors onto newborn cells, and by phasic GABA activity when differentiating neurons receive GABAergic synaptic inputs from inhibitory interneurons of the subgranular zone and hilus [7].

Methods

Results

Conclusion