Abstract
Group I metabotropic glutamate receptors, in particular mGluR5, have been implicated in various forms of synaptic plasticity that are believed to underlie declarative memory. We observed that mGluR5 specifically activated a channel containing TRPC1, an isoform of the canonical family of transient receptor potential (TRPC) channels highly expressed in CA1-3 regions of the hippocampus. TRPC1 is able to form tetrameric complexes with TRPC4 and/or TRPC5 isoforms. TRPC1/4/5 complexes have recently been involved in the efficiency of synaptic transmission in the hippocampus. We therefore used a mouse model devoid of TRPC1 expression to investigate the involvement of mGluR5-TRPC1 pathway in synaptic plasticity and memory formation. Trpc1-/- mice showed alterations in spatial working memory and fear conditioning. Activation of mGluR increased synaptic excitability in neurons from WT but not from Trpc1-/- mice. LTP triggered by a theta burst could not maintain over time in brain slices from Trpc1-/- mice. mGluR-induced LTD was also impaired in these mice. Finally, acute inhibition of TRPC1 by Pico145 on isolated neurons or on brain slices mimicked the genetic depletion of Trpc1 and inhibited mGluR-induced entry of cations and subsequent effects on synaptic plasticity, excluding developmental or compensatory mechanisms in Trpc1-/- mice. In summary, our results indicate that TRPC1 plays a role in synaptic plasticity and spatial working memory processes.
Highlights
The canonical family of transient receptor potential (TRPC) proteins owns seven members (TRPC1 to TRPC7) that form homo- and/or hetero-tetrameric Ca2+-permeable, nonselective cation membrane channels (Minke and Cook, 2002; Owsianik et al, 2006)
Several in vitro studies showed that TRPC1 can form channel complexes with TRPC4 and TRPC5 but not with TRPC3 and TRPC6, and that all other TRPCs exclusively assemble into homo- or hetero-tetramers within their own subfamilies (Hofmann et al, 2002; Alfonso et al, 2008)
Coimmunoprecipitation experiments performed on synaptosomal preparations confirmed the presence of TRPC1/4/5 and TRPC3/6/7 complexes in rat brain (Strubing et al, 2001; Goel et al, 2002)
Summary
The canonical family of transient receptor potential (TRPC) proteins owns seven members (TRPC1 to TRPC7) that form homo- and/or hetero-tetrameric Ca2+-permeable, nonselective cation membrane channels (Minke and Cook, 2002; Owsianik et al, 2006). TRPC channels have diverse functions in the brain (Selvaraj et al, 2010; Bollimuntha et al, 2011; Vennekens et al, 2012). They are involved in neurite outgrowth and axon guidance (Greka et al, 2003; Li et al, 2005; Wang and Poo, 2005), in neural progenitor cells proliferation and differentiation (Li et al, 2012; Du et al, 2017) and in neuronal apoptosis or survival (Tai et al, 2009; He et al, 2016). BrokerLai et al (2017) demonstrated that the TRPC1/4/5 complex is involved presynaptically in the efficiency of synaptic transmission in the hippocampus
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
