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Heteromeric channels formed by TRPC 1, TRPC 4 and TRPC 5 define hippocampal synaptic transmission and working memory
Author(s) -
BrökerLai Jenny,
Kollewe Astrid,
Schindeldecker Barbara,
Pohle Jörg,
Nguyen Chi Vivan,
Mathar Ilka,
Guzman Raul,
Schwarz Yvonne,
Lai Alan,
Weißgerber Petra,
Schwegler Herbert,
Dietrich Alexander,
Both Martin,
Sprengel Rolf,
Draguhn Andreas,
Köhr Georg,
Fakler Bernd,
Flockerzi Veit,
Bruns Dieter,
Freichel Marc
Publication year - 2017
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.15252/embj.201696369
Subject(s) - trpc , transient receptor potential channel , trpc5 , trpc1 , neuroscience , biology , excitatory postsynaptic potential , postsynaptic potential , microbiology and biotechnology , hippocampal formation , neurotransmission , inhibitory postsynaptic potential , receptor , biochemistry
Canonical transient receptor potential ( TRPC ) channels influence various neuronal functions. Using quantitative high‐resolution mass spectrometry, we demonstrate that TRPC 1, TRPC 4, and TRPC 5 assemble into heteromultimers with each other, but not with other TRP family members in the mouse brain and hippocampus. In hippocampal neurons from Trpc1/Trpc4/Trpc5 ‐triple‐knockout ( Trpc1/4/5 −/− ) mice, lacking any TRPC 1‐, TRPC 4‐, or TRPC 5‐containing channels, action potential‐triggered excitatory postsynaptic currents ( EPSC s) were significantly reduced, whereas frequency, amplitude, and kinetics of quantal miniature EPSC signaling remained unchanged. Likewise, evoked postsynaptic responses in hippocampal slice recordings and transient potentiation after tetanic stimulation were decreased. In vivo , Trpc1/4/5 −/− mice displayed impaired cross‐frequency coupling in hippocampal networks and deficits in spatial working memory, while spatial reference memory was unaltered. Trpc1/4/5 −/− animals also exhibited deficiencies in adapting to a new challenge in a relearning task. Our results indicate the contribution of heteromultimeric channels from TRPC 1, TRPC 4, and TRPC 5 subunits to the regulation of mechanisms underlying spatial working memory and flexible relearning by facilitating proper synaptic transmission in hippocampal neurons.