Dataset Information

TARP γ-2 and γ-8 Differentially Control AMPAR Density Across Schaffer Collateral/Commissural Synapses in the Hippocampal CA1 Area.

ABSTRACT: The number of AMPA-type glutamate receptors (AMPARs) at synapses is the major determinant of synaptic strength and varies from synapse to synapse. To clarify the underlying molecular mechanisms, the density of AMPARs, PSD-95, and transmembrane AMPAR regulatory proteins (TARPs) were compared at Schaffer collateral/commissural (SCC) synapses in the adult mouse hippocampal CA1 by quantitative immunogold electron microscopy using serial sections. We examined four types of SCC synapses: perforated and nonperforated synapses on pyramidal cells and axodendritic synapses on parvalbumin-positive (PV synapse) and pravalbumin-negative interneurons (non-PV synapse). SCC synapses were categorized into those expressing high-density (perforated and PV synapses) or low-density (nonperforated and non-PV synapses) AMPARs. Although the density of PSD-95 labeling was fairly constant, the density and composition of TARP isoforms was highly variable depending on the synapse type. Of the three TARPs expressed in hippocampal neurons, the disparity in TARP γ-2 labeling was closely related to that of AMPAR labeling. Importantly, AMPAR density was significantly reduced at perforated and PV synapses in TARP γ-2-knock-out (KO) mice, resulting in a virtual loss of AMPAR disparity among SCC synapses. In comparison, TARP γ-8 was the only TARP expressed at nonperforated synapses, where AMPAR labeling further decreased to a background level in TARP γ-8-KO mice. These results show that synaptic inclusion of TARP γ-2 potently increases AMPAR expression and transforms low-density synapses into high-density ones, whereas TARP γ-8 is essential for low-density or basal expression of AMPARs at nonperforated synapses. Therefore, these TARPs are critically involved in AMPAR density control at SCC synapses.

Significance statement

Although converging evidence implicates the importance of transmembrane AMPA-type glutamate receptor (AMPAR) regulatory proteins (TARPs) in AMPAR stabilization during basal transmission and synaptic plasticity, how they control large disparities in AMPAR numbers or densities across central synapses remains largely unknown. We compared the density of AMPARs with that of TARPs among four types of Schaffer collateral/commissural (SCC) hippocampal synapses in wild-type and TARP-knock-out mice. We show that the density of AMPARs correlates with that of TARP γ-2 across SCC synapses and its high expression is linked to high-density AMPAR expression at perforated type of pyramidal cell synapses and synapses on parvalbumin-positive interneurons. In comparison, TARP γ-8 is the only TARP expressed at nonperforated type of pyramidal cell synapses, playing an essential role in low-density or basal AMPAR expression.

SUBMITTER: Yamasaki M

PROVIDER: S-EPMC6601775 | biostudies-literature | 2016 Apr

REPOSITORIES: biostudies-literature

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TARP γ-2 and γ-8 Differentially Control AMPAR Density Across Schaffer Collateral/Commissural Synapses in the Hippocampal CA1 Area.

Yamasaki Miwako M Fukaya Masahiro M Yamazaki Maya M Azechi Hirotsugu H Natsume Rie R Abe Manabu M Sakimura Kenji K Watanabe Masahiko M

The Journal of neuroscience : the official journal of the Society for Neuroscience 20160401 15

The number of AMPA-type glutamate receptors (AMPARs) at synapses is the major determinant of synaptic strength and varies from synapse to synapse. To clarify the underlying molecular mechanisms, the density of AMPARs, PSD-95, and transmembrane AMPAR regulatory proteins (TARPs) were compared at Schaffer collateral/commissural (SCC) synapses in the adult mouse hippocampal CA1 by quantitative immunogold electron microscopy using serial sections. We examined four types of SCC synapses: perforated an ...[more]

PMID: 27076426

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Project description:CA1 pyramidal neurons receive two distinct excitatory inputs that are each capable of influencing hippocampal output and learning and memory. The Schaffer collateral (SC) input from CA3 axons onto the more proximal dendrites of CA1 is part of the trisynaptic circuit, which originates in Layer II of the entorhinal cortex (EC). The temporoammonic (TA) pathway to CA1 provides input directly from Layer III of the EC onto the most distal dendrites of CA1 pyramidal cells, and is involved in spatial memory and memory consolidation. We have previously described a developmental decrease in short-term facilitation from juvenile (P13-18) to young adult (P28-42) rats at SC synapses that is due to feedback inhibition via synaptically activated mGluR1 on CA1 interneurons. It is not known how short-term changes in synaptic strength are regulated at TA synapses, nor is it known how short-term plasticity is balanced at SC and TA inputs during development. Here we describe a novel developmental increase in short-term facilitation at TA synapses, which is the opposite of the decrease in facilitation occurring at SC synapses. Although short-term facilitation is much lower at TA synapses when compared with SC synapses in juveniles, short-term plasticity at SC and TA synapses converges at similar levels of paired-pulse facilitation in the young adult rat. However, in young adults CA3-CA1 synapses still exhibit more facilitation than TA-CA1 synapses during physiologically-relevant activity, suggesting that the two pathways are each poised to uniquely modulate CA1 output in an activity-dependent manner. Finally, we show that there is a developmental decrease in the initial release probability at TA synapses that underlies their developmental decrease in facilitation, but no developmental change in release probability at SC synapses. This represents a fundamental difference in the presynaptic function of the two major inputs to CA1, which could alter the flow of information in hippocampus during development.

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Dataset Information

TARP γ-2 and γ-8 Differentially Control AMPAR Density Across Schaffer Collateral/Commissural Synapses in the Hippocampal CA1 Area.

Significance statement

Publications

TARP γ-2 and γ-8 Differentially Control AMPAR Density Across Schaffer Collateral/Commissural Synapses in the Hippocampal CA1 Area.

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