Dopamine Modulates Homeostatic Excitatory Synaptic Plasticity of Immature Dentate Granule Cells in Entorhino-Hippocampal Slice Cultures.

Andreas Strehl,Stephan Wolfgang Schwarzacher,Tijana Radic,Christos Galanis,Thomas Deller,Andreas Vlachos

doi:10.3389/fnmol.2018.00303

Andreas Strehl, Stephan Wolfgang Schwarzacher + Show 4 more

Open Access

https://doi.org/10.3389/fnmol.2018.00303

Copy DOI

Abstract

Homeostatic plasticity mechanisms maintain neurons in a stable state. To what extent these mechanisms are relevant during the structural and functional maturation of neural tissue is poorly understood. To reveal developmental changes of a major homeostatic plasticity mechanism, i.e., homeostatic excitatory synaptic plasticity, we analyzed 1-week- and 4-week-old entorhino-hippocampal slice cultures and investigated the ability of immature and mature dentate granule cells (GCs) to express this form of plasticity. Our experiments demonstrate that immature GCs are capable of adjusting their excitatory synaptic strength in a compensatory manner at early postnatal stages, i.e., in 1-week-old preparations, as is the case for mature GCs. This ability of immature dentate GCs is absent in 4-week-old slice cultures. Further investigations into the signaling pathways reveal an important role of dopamine (DA), which prevents homeostatic synaptic up-scaling of immature GCs in young cultures, whereas it does not affect immature and mature GCs in 4-week-old preparations. Together, these results disclose the ability of immature GCs to express homeostatic synaptic plasticity during early postnatal development. They hint toward a novel role of dopaminergic signaling, which may gate activity-dependent changes of newly born neurons by blocking homeostasis.

Highlights

Homeostatic plasticity plays a fundamental role in maintaining neural networks in a stable state
Our experiments demonstrate that immature granule cells (GCs) are capable of adjusting their excitatory synaptic strength in a compensatory manner at early postnatal stages, i.e., in 1-week-old preparations, as is the case for mature GCs
Individual dentate GCs in the inner part of the GC layer (GCL) were patched in 1-week-old slice cultures, and amino-3hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptormediated miniature excitatory postsynaptic current (mEPSC) were recorded from TTX-treated cultures (2 μM; 3 days) as well as age-/time-matched vehicle-treated controls (Figure 1)

Summary

Introduction

Homeostatic plasticity plays a fundamental role in maintaining neural networks in a stable state. Among the best studied forms is homeostatic synaptic plasticity, which adjusts synaptic strength in a compensatory manner to changes in network activity (Davis, 2006; Marder and Goaillard, 2006; Turrigiano, 2008; Pozo and Goda, 2010). Numerous studies have addressed the cellular and molecular mechanisms of homeostatic synaptic plasticity in various experimental conditions (e.g., Marder and Goaillard, 2006; Turrigiano, 2012; Tien and Kerschensteiner, 2018). Its relevance in neural development and maturation remains poorly understood In this context, we hypothesized that homeostatic plasticity, i.e., negative feedback mechanisms that aim at stabilizing neural networks by preventing major changes in network structure and function, may hinder the efficient activity-dependent maturation and network integration of neurons.

Methods

Results

Conclusion