PMID- 37545882
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20230808
IS  - 1662-5102 (Print)
IS  - 1662-5102 (Electronic)
IS  - 1662-5102 (Linking)
VI  - 17
DP  - 2023
TI  - Overexpression of the autism candidate gene Cyfip1 pathologically enhances 
      olivo-cerebellar signaling in mice.
PG  - 1219270
LID - 10.3389/fncel.2023.1219270 [doi]
LID - 1219270
AB  - Cyfip1, the gene encoding cytoplasmic FMR1 interacting protein 1, has been of 
      interest as an autism candidate gene for years. A potential role in autism 
      spectrum disorder (ASD) is suggested by its location on human chromosome 
      15q11-13, an instable region that gives rise to a variety of copy number 
      variations associated with syndromic autism. In addition, the CYFIP1 protein acts 
      as a binding partner to Fragile X Messenger Ribonucleoprotein (FMRP) in the 
      regulation of translation initiation. Mutation of FMR1, the gene encoding FMRP, 
      causes Fragile X syndrome, another form of syndromic autism. Here, in mice 
      overexpressing CYFIP1, we study response properties of cerebellar Purkinje cells 
      to activity of the climbing fiber input that originates from the inferior olive 
      and provides an instructive signal in sensorimotor input analysis and plasticity. 
      We find that CYFIP1 overexpression results in enhanced localization of the 
      synaptic organizer neurexin 1 (NRXN1) at climbing fiber synaptic input sites on 
      Purkinje cell primary dendrites and concomitant enhanced climbing fiber synaptic 
      transmission (CF-EPSCs) measured using whole-cell patch-clamp recordings from 
      Purkinje cells in vitro. Moreover, using two-photon measurements of 
      GCaMP6f-encoded climbing fiber signals in Purkinje cells of intact mice, we 
      observe enhanced responses to air puff stimuli applied to the whisker field. 
      These findings resemble our previous phenotypic observations in a mouse model for 
      the human 15q11-13 duplication, which does not extend to the Cyfip1 locus. Thus, 
      our study demonstrates that CYFIP1 overexpression shares a limited set of 
      olivo-cerebellar phenotypes as those resulting from an increased number of copies 
      of non-overlapping genes located on chromosome 15q11-13.
CI  - Copyright (c) 2023 Busch, Simmons, Gama, Du, Longo, Gomez, Klann and Hansel.
FAU - Busch, Silas E
AU  - Busch SE
AD  - Department of Neurobiology, The University of Chicago, Chicago, IL, United 
      States.
FAU - Simmons, Dana H
AU  - Simmons DH
AD  - Department of Neurobiology, The University of Chicago, Chicago, IL, United 
      States.
FAU - Gama, Eric
AU  - Gama E
AD  - Department of Neurology, The University of Chicago, Chicago, IL, United States.
FAU - Du, Xiaofei
AU  - Du X
AD  - Department of Neurology, The University of Chicago, Chicago, IL, United States.
FAU - Longo, Francesco
AU  - Longo F
AD  - Center for Neural Science, New York University, New York, NY, United States.
AD  - Institute for Neuroscience and Physiology, University of Gothenburg, Gothenburg, 
      Sweden.
FAU - Gomez, Christopher M
AU  - Gomez CM
AD  - Department of Neurology, The University of Chicago, Chicago, IL, United States.
FAU - Klann, Eric
AU  - Klann E
AD  - Center for Neural Science, New York University, New York, NY, United States.
FAU - Hansel, Christian
AU  - Hansel C
AD  - Department of Neurobiology, The University of Chicago, Chicago, IL, United 
      States.
LA  - eng
PT  - Journal Article
DEP - 20230720
PL  - Switzerland
TA  - Front Cell Neurosci
JT  - Frontiers in cellular neuroscience
JID - 101477935
PMC - PMC10399232
OTO - NOTNLM
OT  - CYFIP1 OE transgenic
OT  - Purkinje cell
OT  - autism
OT  - cerebellum
OT  - electrophysiology
OT  - two-photon Ca2+ imaging
COIS- The authors declare that the research was conducted in the absence of any 
      commercial or financial relationships that could be construed as a potential 
      conflict of interest.
EDAT- 2023/08/07 06:42
MHDA- 2023/08/07 06:43
PMCR- 2023/01/01
CRDT- 2023/08/07 04:30
PHST- 2023/05/08 00:00 [received]
PHST- 2023/07/06 00:00 [accepted]
PHST- 2023/08/07 06:43 [medline]
PHST- 2023/08/07 06:42 [pubmed]
PHST- 2023/08/07 04:30 [entrez]
PHST- 2023/01/01 00:00 [pmc-release]
AID - 10.3389/fncel.2023.1219270 [doi]
PST - epublish
SO  - Front Cell Neurosci. 2023 Jul 20;17:1219270. doi: 10.3389/fncel.2023.1219270. 
      eCollection 2023.