Developmental modification of synaptic NMDAR composition and maturation of glutamatergic synapses: matching postsynaptic slots with receptor pegs
Authors: Daniel N Cox
Kevin C Zhou
Theodore C Dumas
Mary E Hanks
Erin M Sanders
Michael A Nguyen
Kawthar A Yusuf
Journal: Biological Bulletin (2013)
Discipline: BIOLOGY & BIOCHEMISTRY
Keywords: ionotropic glutamate receptors; synaptic plasticity; metaplasticity; synaptic development; glutamate receptor subunits
Affiliations: Molecular Neuroscience Department, Krasnow Institute for Advanced Study, George Mason University, Fairfax, VA 22030, USA.

Abstract:  The numbers and types of ionotropic glutamate receptors at most vertebrate central excitatory synapses are altered as a function of changes in input activity patterns that occur during postnatal development. Activity-dependent developmental alterations in glutamate receptors underlie lasting changes in synaptic efficacy (plasticity) and metaplasticity (the plasticity of synaptic plasticity), which are critical elements of normal brain maturation. Understanding the specific involvement of glutamate receptors in synaptic development and function is made multiplicatively complex by the existence of a large number of glutamate receptor subunits, numerous subunit-specific amino acid sequences that regulate receptor function, and subunit-specific synaptic insertion restrictions imposed by associated anchoring proteins. Many receptor properties are altered when subunits are switched, so it is unclear which individual receptor property or properties underlie changes in synaptic function and plasticity during postnatal development. As a result, a more detailed understanding of the factors that regulate synaptic and cognitive development will involve mutations in glutamate receptor subunits that separate individual receptor properties and permit synaptic insertion at both immature and mature synapses in genetically modified organisms. This position paper focuses on structural modifications in N-methyl-d-aspartate receptors (NMDARs) that occur during postnatal forebrain development and attempts to provide a method for pursuing a more complete understanding of the functional ramifications of developmental alterations in NMDAR subunit composition. 

Retracted: No

PubPeer comments:
 1) The study authors point out  PRISMA statement was used to identify, assess and synthesize the selected studies but PRISMA 2009 is a reporting guideline meant to help authors **report** how they conducted their systematic review. PRISMA 2009 authors explicitly explain in its scope that  It does not address directly or in a detailed manner the conduct of systematic reviews, for which other guides are available [refs] (Liberati, 2009). The authors therefore likely followed other **conduct** guidance which they may cite instead (such as the Cochrane Handbook, JBI or Campbell guidance), this would for instance clarify how they selected the EPOC, CEBM and CASP tools to assess included studies. 2) Item 7 of PRISMA 2009 notes  At a minimum, for each database searched, authors should report the database [...] . The authors report searching 6 databases but only name PsycInfo and Scopus in the main text; which were the other 4 databases then? 3) Item 8 of PRISMA 2009 notes  Present the full electronic search strategy for at least one major database, including any limits used, such that it could be repeated. (its update, PRISMA 2020 goes even further, recommending presenting all full search strategies). The authors do report 1 search strategy but I find it difficult to know what they actually did because of their use of  such as ... or  i.e. ; for instance :  [...] search limitations, **such as** title, keywords and abstract, original articles and English language were used in Scopus. Does this mean other limitations filters were used? If not, I would have expected the authors to not say  such as . 4) The authors report that studies were deemed of  mainly satisfactory quality based on their assessments using the EPOC, CEBM and CASP tool. I find this statement highly subjective and would have liked them to report in more depth how the results of EPOC, CEBM and CASP (not shown?) support this statement. Liberati, A., Altman, D. G., Tetzlaff, J., Mulrow, C., Gu00f8tzsche, P. C., Ioannidis, J. P. A., Clarke, M., Devereaux, P. J., Kleijnen, J., Moher, D. (2009). The PRISMA Statement for Reporting Systematic Reviews and Meta-Analyses of Studies That Evaluate Health Care Interventions: Explanation and Elaboration. PLoS Medicine, 6(7), e1000100. https: doi.org 10.1371 journal.pmed.1000100 Page, M. J., McKenzie, J. E., Bossuyt, P. M., Boutron, I., Hoffmann, T. C., Mulrow, C. D., Shamseer, L., Tetzlaff, J. M., Akl, E. A., Brennan, S. E., Chou, R., Glanville, J., Grimshaw, J. M., Hru00f3bjartsson, A., Lalu, M. M., Li, T., Loder, E. W., Mayo-Wilson, E., McDonald, S., u2026 Moher, D. (2021). The PRISMA 2020 statement: an updated guideline for reporting systematic reviews. BMJ, n71. https: doi.org 10.1136 bmj.n71 ,