Abstract

Hippocampal GABAergic interneurons play key roles in regulating principal cell activity and plasticity. Interneurons located in stratum oriens/alveus (O/A INs) receive excitatory inputs from CA1 pyramidal cells and express a Hebbian form of long-term potentiation (LTP) at their excitatory input synapses. This LTP requires the activation of metabotropic glutamate receptors 1a (mGluR1a) and Ca2+ entry via transient receptor potential (TRP) channels. However, the type of TRP channels involved in synaptic transmission at these synapses remains largely unknown. Using patch-clamp recordings, we show that slow excitatory postsynaptic currents (EPSCs) evoked in O/A INs are dependent on TRP channels but may be independent of phospholipase C. Using reverse transcription polymerase chain reaction (RT-PCR) we found that mRNA for TRPC 1, 3–7 was present in CA1 hippocampus. Using single-cell RT-PCR, we found expression of mRNA for TRPC 1, 4–7, but not TRPC3, in O/A INs. Using co-immunoprecipitation assays in HEK-293 cell expression system, we found that TRPC1 and TRPC4 interacted with mGluR1a. Co-immunoprecipitation in hippocampus showed that TRPC1 interacted with mGluR1a. Using immunofluorescence, we found that TRPC1 co-localized with mGluR1a in O/A IN dendrites, whereas TRPC4 localization appeared limited to O/A IN cell body. Down-regulation of TRPC1, but not TRPC4, expression in O/A INs using small interfering RNAs prevented slow EPSCs, suggesting that TRPC1 is an obligatory TRPC subunit for these EPSCs. Our findings uncover a functional role of TRPC1 in mGluR1a-mediated slow excitatory synaptic transmission onto O/A INs that could be involved in Hebbian LTP at these synapses.

Highlights

  • Hippocampal GABAergic interneurons represent a diverse population of inhibitory cells that are involved in gating information flow and computations by controlling principal cells activity [1, 2]

  • We found that O/A Somatostatin interneurons (INs) express mRNA for TRPC1, 4–7, and that TRPC1 was co-localized with metabotropic glutamate receptors 1a (mGluR1a) in O/A IN dendrites

  • TRPC1 is a necessary component of mGluR1a-mediated slow excitatory synaptic transmission in O/A INs, uncovering a possible role in induction of Hebbian long-term potentiation (LTP) at these synapses

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Summary

Introduction

Hippocampal GABAergic interneurons represent a diverse population of inhibitory cells that are involved in gating information flow and computations by controlling principal cells activity [1, 2]. Interneuron functions are not static and inhibitory cells express short- and longterm plasticity of their synaptic inputs and outputs [3, 4]. High frequency stimulation of excitatory inputs onto O/A INs elicit slow excitatory postsynaptic currents (EPSCs) that are mediated by mGluR1a and nonselective cationic channels of the transient receptor potential (TRP) family [12]. Ca2+ influx via TRP channels following mGluR1a activation is necessary for LTP induction at O/A IN excitatory synapses [13]. Which TRP channel is involved in transmission and plasticity at these synapses remains unknown

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