Development of Depotentiation in Adult-Born Dentate Granule Cells.

Xiaoqing Tao,Ning Sun,Yangling Mu

doi:10.3389/fcell.2019.00236

Abstract

Activity-dependent synaptic plasticity, i.e., long-term potentiation (LTP), long-term depression (LTD) and LTP reversal, is generally thought to make up the cellular mechanism underlying learning and memory in the mature brain, in which N-methyl-D-aspartate subtype of glutamate (NMDA) receptors and neurogenesis play important roles. LTP reversal may be the mechanism of forgetting and may mediate many psychiatric disorders, such as schizophrenia, but the specific mechanisms underlying these disorders remain unclear. In addition, LTP reversal during the development of adult-born dentate granule cells (DGCs) remains unknown. We found that the expression of the NMDA receptor subunits NR2A and NR2B displayed dynamic changes during the development of postnatal individuals and the maturation of adult-born neurons and was coupled with the change in LTP reversal. The susceptibility of LTP reversal progressively increases with the rise in the expression of NR2A during the development of postnatal individual and adult-born neurons. In addition, NMDA receptor subunits NR2A, but not NR2B, mediated LTP reversal in the DGCs of the mouse hippocampus.

Highlights

Activity-dependent synaptic plasticity is generally believed to be the cellular mechanism underlying the developmental modification of neuronal circuits (Zhang and Poo, 2001) as well as learning and memory in the animal brain (Martin et al, 2000; Malenka and Bear, 2004; Nabavi et al, 2014)
To evaluate the long-term potentiation (LTP) and LTP reversal, excitatory postsynaptic potentials (EPSPs) of dentate granule cells (DGCs) were recorded in current-clamp mode with low-frequency stimulation (20 s per interval) of the medial perforant pathway (Figure 1A)
To examine the synaptic plasticity of DGCs, we used a theta-burst stimulation (TBS) paradigm (Supplementary Figure S1) that mimics the physiological firing pattern commonly observed in hippocampal DGCs in vivo (Skaggs et al, 1996) to induce LTP (Larson and Lynch, 1986)

Summary

Introduction

Activity-dependent synaptic plasticity is generally believed to be the cellular mechanism underlying the developmental modification of neuronal circuits (Zhang and Poo, 2001) as well as learning and memory in the animal brain (Martin et al, 2000; Malenka and Bear, 2004; Nabavi et al, 2014). It has been recognized that LTP can be reversed by subsequent electrical activity in the CNS, namely, LTP reversal (Zhou and Poo, 2004). The LTP reversal was first described by Hesse and Teyler (1976) They demonstrated that electroconvulsive seizure activity can reverse the low frequency tetanic stimulation-induced LTP in the rat hippocampus CA1 (Hesse and Teyler, 1976). Poo’s group found that activity-induced LTP can be quickly reversed either by spontaneous activity of subsequent tectal neurons or by exposure to random visual

Methods

Results

Conclusion