DOI: 10.1073/pnas.0702023104. Regulation of CNS synapses by neuronal MHC class I

Regulation of CNS synapses by neuronal MHC class I

10.1073/pnas.0702023104

Crossref journal-article

Proceedings of the National Academy of Sciences

Proceedings of the National Academy of Sciences (341)

Abstract

Until recently, neurons in the healthy brain were considered immune-privileged because they did not appear to express MHC class I (MHCI). However, MHCI mRNA was found to be regulated by neural activity in the developing visual system and has been detected in other regions of the uninjured brain. Here we show that MHCI regulates aspects of synaptic function in response to activity. MHCI protein is colocalized postsynaptically with PSD-95 in dendrites of hippocampal neurons. In vitro , whole-cell recordings of hippocampal neurons from β2m/TAP1 knockout (KO) mice, which have reduced MHCI surface levels, indicate a 40% increase in mini-EPSC (mEPSC) frequency. mEPSC frequency is also increased 100% in layer 4 cortical neurons. Similarly, in KO hippocampal cultures, there is a modest increase in the size of presynaptic boutons relative to WT, whereas postsynaptic parameters (PSD-95 puncta size and mEPSC amplitude) are normal. In EM of intact hippocampus, KO synapses show a corresponding increase in vesicles number. Finally, KO neurons in vitro fail to respond normally to TTX treatment by scaling up synaptic parameters. Together, these results suggest that postsynaptically localized MHCl acts in homeostatic regulation of synaptic function and morphology during development and in response to activity blockade. The results also imply that MHCI acts retrogradely across the synapse to translate activity into lasting change in structure.

Bibliography

Goddard, C. A., Butts, D. A., & Shatz, C. J. (2007). Regulation of CNS synapses by neuronal MHC class I. Proceedings of the National Academy of Sciences, 104(16), 6828â6833.

Authors 3

C. Alex Goddard (first)
Daniel A. Butts (additional)
Carla J. Shatz (additional)

References 55 Referenced 260

Dates

Type	When
Created	18 years, 4 months ago (April 9, 2007, 8:59 p.m.)
Deposited	3 years, 4 months ago (April 12, 2022, 4:29 p.m.)
Indexed	1 week, 3 days ago (Aug. 21, 2025, 12:53 p.m.)
Issued	18 years, 4 months ago (April 17, 2007)
Published	18 years, 4 months ago (April 17, 2007)
Published Online	18 years, 4 months ago (April 17, 2007)
Published Print	18 years, 4 months ago (April 17, 2007)

Funders 0

None

BibTeX

@article{Goddard_2007, title={Regulation of CNS synapses by neuronal MHC class I}, volume={104}, ISSN={1091-6490}, url={http://dx.doi.org/10.1073/pnas.0702023104}, DOI={10.1073/pnas.0702023104}, number={16}, journal={Proceedings of the National Academy of Sciences}, publisher={Proceedings of the National Academy of Sciences}, author={Goddard, C. Alex and Butts, Daniel A. and Shatz, Carla J.}, year={2007}, month=apr, pages={6828–6833} }

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