Differential inhibition onto developing and mature granule cells generates high-frequency filters with variable gain.

María Belén Pardi,Mora Belén Ogando,Antonia Marin-Burgin,Alejandro F Schinder

doi:10.7554/elife.08764

Abstract

Adult hippocampal neurogenesis provides the dentate gyrus with heterogeneous populations of granule cells (GC) originated at different times. The contribution of these cells to information encoding is under current investigation. Here, we show that incoming spike trains activate different populations of GC determined by the stimulation frequency and GC age. Immature GC respond to a wider range of stimulus frequencies, whereas mature GC are less responsive at high frequencies. This difference is dictated by feedforward inhibition, which restricts mature GC activation. Yet, the stronger inhibition of mature GC results in a higher temporal fidelity compared to that of immature GC. Thus, hippocampal inputs activate two populations of neurons with variable frequency filters: immature cells, with wide-range responses, that are reliable transmitters of the incoming frequency, and mature neurons, with narrow frequency response, that are precise at informing the beginning of the stimulus, but with a sparse activity.

Highlights

The dentate gyrus (DG) is the main entrance of information to the hippocampus (Andersen et al, 1971)
We selected 4-week-old neurons as immature granule cells (GC) because this is the earliest stage at which adult-born GC can be reliably activated by an excitatory drive (Mongiat et al, 2009), exhibit funtional properties that distinguish them from mature neurons (Wang et al, 2000; Snyder et al, 2001; Schmidt-Hieber et al, 2004; Esposito et al, 2005; Ge et al, 2007; Marın-Burgin et al, 2012), and are already connected with postsynaptic targets (Gu et al, 2012; Marın-Burgin et al, 2012; Temprana et al, 2015)
The results demonstrate that the activation differences between immature and mature GC are governed by the recruitment of feedforward inhibitory circuits

Summary

Introduction

The dentate gyrus (DG) is the main entrance of information to the hippocampus (Andersen et al, 1971). New born neurons are initially contacted by dendritic GABAergic terminals, followed by glutamatergic axons and last by GABAergic perisomatic contacts. In parallel, their membrane resistance decreases and excitability becomes mature (Esposito et al, 2005; Ge et al, 2006). Adult-born neurons achieve a functional profile that is indistinguishable from that of all other GC as reflected by their inputs, intrinsic membrane properties, and firing behavior (Laplagne et al, 2006, 2007). Adult-born GC form functional glutamatergic synapses onto DG interneurons and CA3 pyramidal cells (Toni et al, 2008; Temprana et al, 2015), indicating that new neurons receive, process, and convey information onto target neurons and participate in hippocampal function

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Results

Conclusion