Delayed Coupling to Feedback Inhibition during a Critical Period for the Integration of Adult-Born Granule Cells

Abstract

SUMMARY Developing granule cells (GCs) of the adult dentate gyrus undergo a critical period of enhanced activity and synaptic plasticity before becoming mature. The impact of developing GCs on the activity of preexisting dentate circuits remains unknown. Here we combine optogenetics, acute slice electrophysiology, and in vivo chemogenetics to activate GCs at different stages of maturation to study the recruitment of local target networks. We show that immature (four-week-old) GCs can efficiently drive distal CA3 targets, but poorly activate proximal interneurons responsible for feedback inhibition (FBI). As new GCs transition towards maturity, they reliably recruit GABAergic feedback loops that restrict spiking of neighbor GCs, a mechanism that would promote sparse coding. Such inhibitory loop impinges only weakly in new cohorts of young GCs. A computational model reveals that the delayed coupling of new GCs to FBI could be crucial to achieve a fine-grain representation of novel inputs in the dentate gyrus.

Optogenetics: 10 years of microbial opsins in neuroscience

“…Learning itself has been studied with optogenetics in ventral striatum and amygdala 143,144 , as well as in the hippocampus 138 , and inputs to the hippocampal formation have been studied in some detail with regard to causal roles in learning, navigation and information flow 145–147 . Finally, precisely timed activity patterns in diverse well-defined cell types, projections and populations have been causally implicated in synaptic plasticity 148,149 , wiring and microcircuit plasticity 150,151 , and in long-timescale devel-opmental 152,153 and adaptive changes such as activity-dependent myelination 154 and adult neurogenesis 155,156 .…”

Corruption of the dentate gyrus by “dominant” granule cells: Implications for dentate gyrus function in health and disease

“…This idea is based on empirical data showing that activation of adult-born GCs selectively, using optogenetics, causes both inhibition and excitation of other GCs (Drew et al, 2013). Previous studies also have shown that during maturation, adult-born GCs display a dynamic set of intrinsic and synaptic characteristics that make them vary their role in the DG-CA3 circuitry (Dieni et al, 2013; Temprana et al, 2015). …”

Neurogenesis in Cancun: where science meets the sea

“…He also presented recently published (Temprana et al, 2015) and unpublished data using optogenetics and chemogenetics to map the local target networks activated by adult-born neurons. Shaoyu Ge (Stonybrook University, New York, USA) continued the theme of circuit-level analysis by defining the mechanisms that control the initiation of circuit integration of adult-born neurons.…”