Format

Send to

Choose Destination
Neuropharmacology. 2014 Mar;78:38-44. doi: 10.1016/j.neuropharm.2013.07.009. Epub 2013 Aug 2.

Molecular mechanisms of homeostatic synaptic downscaling.

Author information

1
Neuroscience Center of Excellence, Louisiana State University Health Science Center, New Orleans, LA 70112, USA.
2
Neuroscience Center of Excellence, Louisiana State University Health Science Center, New Orleans, LA 70112, USA. Electronic address: hugh_xia@yahoo.com.

Abstract

Homeostatic synaptic downscaling is a negative feedback response to chronic elevated network activity to reduce the firing rate of neurons. This form of synaptic plasticity decreases the strength of individual synapses to the same proportion, or in a multiplicative manner. Because of this, synaptic downscaling has been hypothesized to counter the potential run-away excitation due to Hebbian type of long term potentiation (LTP), while preserving relative synaptic weight encoded in individual synapses and thus memory information. In this article, we will review the current knowledge on the signaling and molecular mechanisms of synaptic downscaling. Specifically, we focus on three general areas. First the functional roles of several immediate early genes such as Plk2, Homer1a, Arc and Narp are discussed. Secondly, we examine the current knowledge on the regulation of synaptic protein levels by ubiquitination and transcriptional repression in synaptic downscaling. Thirdly, we review the dynamics of signaling molecules such as kinases and phosphatases critical for synaptic downscaling, and their regulation of synaptic scaffolding proteins. Finally we briefly discuss the heterogeneity of homeostatic synaptic downscaling mechanisms. This article is part of the Special Issue entitled 'Homeostatic Synaptic Plasticity'.

KEYWORDS:

Immediate early genes; Phosphorylation; Proteasome degradation; Synapse; Synaptic depression; Synaptic scaling

[Indexed for MEDLINE]

Supplemental Content

Full text links

Icon for Elsevier Science
Loading ...
Support Center