Summary: The strength of a memory depends upon the number of receptors in a synapse, researchers report.
Source: UC Davis.
When we create a memory, a pattern of connections forms between neurons in the brain. New work from UC Davis shows how these connections can be strengthened or weakened at a molecular level. The study is published Feb. 27 in the journal Cell Reports.
Neurons branch into many small fibers, called dendrites, that connect to other neurons across tiny gaps called synapses. Messages travel across synapses as chemical signals: A molecule, or neurotransmitter, is released on one side of the synapse and connects with a receptor on the other side, a bit like tossing a ball and a fielder catching it in a mitt.
One of the most important of these catcher’s mitts is the AMPA-type glutamate receptor, responsible for fast synaptic transmission within the brain, said Elva Diaz, associate professor of pharmacology at UC Davis and senior author on the paper. The AMPA receptors are embedded in the cell membrane but quite mobile and can add to or take away from the synapse by moving in or out of it, she said.
“The idea is that when a synapse experiences signaling that could lead to a new memory, it needs to recruit new receptors,” she said. More receptors in the synapse means a stronger memory – just as bringing more fielders out of the dugout will mean more balls get caught.
Diaz’ team is trying to figure out how this movement of receptors in and out of the synapse is regulated, especially in cells of the hippocampus, a small structure within the brain that is crucial to memory function. They have now identified a protein called SynDIG4 that interacts with AMPA receptors and appears to establish a reserve pool of receptors outside the synapse that can be quickly recruited to strengthen memories.
Working with researchers at the UC Davis MIND Institute, the team was able to test the cognitive function of gene-knockout mice that lack SynDIG4. These mice, although otherwise normal, fail at simple memory tasks such as navigating a maze. They seem to have essentially no memory.
SynDIG4 is part of a highly-conserved family of proteins found in humans and other animals, Diaz said. In future work, they plan to try to figure out exactly how SynDIG4 modulates synaptic plasticity, working in mice and cultured cells.
Additional authors on the study are: Lucas Matt, Lyndsey M. Kirk, George Chenaux, David J. Speca, Kristopher Plambeck and Johannes Hell, UC Davis Department of Pharmacology; Kyle Puhger, Michael Pride, Jill Silverman and Jacqueline Crawley, UC Davis MIND Institute; ?Mohammad Qneibi, Tomer Haham and Yael Stern-Bach, Institute for Medical Research Israel-Canada, The Hebrew University-Hadassah Medical School, Jerusalem.
Funding: The work was supported by grants from the NIH, NSF, and the Whitehall Foundation.
Source: Andy Fell – UC Davis
Publisher: Organized by NeuroscienceNews.com.
Image Source: NeuroscienceNews.com image is adapted from the UC Davis news release.
Original Research: Open access research in Cell Reports.
SynDIG4/Prrt1 Is Required for Excitatory Synapse Development and Plasticity Underlying Cognitive Function
•SynDIG4 affects AMPAR biophysical properties in a subunit-dependent manner
•Loss of SynDIG4 results in reduced extrasynaptic AMPAR and weaker synapses
•SynDIG4 is necessary for tetanus-induced, but not theta-burst, LTP
•SynDIG4 KO mice exhibit deficits in two independent cognitive behavior tasks
Altering AMPA receptor (AMPAR) content at synapses is a key mechanism underlying the regulation of synaptic strength during learning and memory. Previous work demonstrated that SynDIG1 (synapse differentiation-induced gene 1) encodes a transmembrane AMPAR-associated protein that regulates excitatory synapse strength and number. Here we show that the related protein SynDIG4 (also known as Prrt1) modifies AMPAR gating properties in a subunit-dependent manner. Young SynDIG4 knockout (KO) mice have weaker excitatory synapses, as evaluated by immunocytochemistry and electrophysiology. Adult SynDIG4 KO mice show complete loss of tetanus-induced long-term potentiation (LTP), while mEPSC amplitude is reduced by only 25%. Furthermore, SynDIG4 KO mice exhibit deficits in two independent cognitive assays. Given that SynDIG4 colocalizes with the AMPAR subunit GluA1 at non-synaptic sites, we propose that SynDIG4 maintains a pool of extrasynaptic AMPARs necessary for synapse development and function underlying higher-order cognitive plasticity.