T-type calcium channels contribute to NMDA receptor independent synaptic plasticity in hippocampal regular-spiking oriens-alveus interneurons.

Elizabeth Nicholson,Dimitri M Kullmann

doi:10.1113/jp273695

Abstract

Key points Regular‐spiking interneurons in the hippocampal stratum oriens exhibit a form of long‐term potentiation of excitatory transmission that is independent of NMDA receptors but requires co‐activation of Ca2+‐permeable AMPA receptors and group I metabotropic glutamate receptors.We show that T‐type Ca2+ channels are present in such interneurons.Blockade of T‐type currents prevents the induction of long‐term potentiation, and also interferes with long‐lasting potentiation induced either by postsynaptic trains of action potentials or by pairing postsynaptic hyperpolarization with activation of group I metabotropic receptors.Several Ca2+ sources thus converge on the induction of NMDA receptor independent synaptic plasticity. NMDA receptor independent long‐term potentiation (LTP) in hippocampal stratum oriens‐alveus (O/A) interneurons requires co‐activation of postsynaptic group I metabotropic glutamate receptors (mGluRs) and Ca2+‐permeable AMPA receptors. The rectification properties of such AMPA receptors contribute to the preferential induction of LTP at hyperpolarized potentials. A persistent increase in excitatory transmission can also be triggered by exogenous activation of group I mGluRs at the same time as the interneuron is hyperpolarized, or by postsynaptic trains of action potentials in the absence of presynaptic stimulation. In the present study, we identify low‐threshold transient (T‐type) channels as a further source of Ca2+ that contributes to synaptic plasticity. T‐type Ca2+ currents were detected in mouse regular‐spiking O/A interneurons. Blocking T‐type currents pharmacologically prevented LTP induced by high‐frequency stimulation of glutamatergic axons, or by application of the group I mGluR agonist dihydroxyphenylglycine, paired with postsynaptic hyperpolarization. T‐type current blockade also prevented synaptic potentiation induced by postsynaptic action potential trains. Several sources of Ca2+ thus converge on NMDA receptor independent LTP induction in O/A interneurons.

Highlights

Long-term potentiation (LTP) in hippocampal interneurons depends critically on postsynaptic Ca2+ signalling (Cowan et al 1998; Alle et al 2001; Lapointe et al 2004; Galvan et al 2008; Nicholson & Kullmann, 2014)
Several interneuron subtypes, predominantly in strata pyramidale and oriens, exhibit NMDA receptor (NMDAR) independent LTP, which instead depends on both Ca2+-permeable AMPA receptors (CP-AMPARs) and group I metabotropic glutamate receptors (Perez et al 2001; Lapointe et al 2004; Lamsa et al 2007; Oren et al 2009; Le Duigou & Kullmann, 2011; Roux et al 2013)
We recently reported that LTP can be elicited when recording from regularspiking oriens-alveus (O/A) interneurons in the whole-cell configuration of the patch clamp method, with polyamines omitted from the pipette solution to relieve voltage-dependent blockade of CP-AMPARs (Nicholson & Kullmann, 2014)

Summary

Introduction

Long-term potentiation (LTP) in hippocampal interneurons depends critically on postsynaptic Ca2+ signalling (Cowan et al 1998; Alle et al 2001; Lapointe et al 2004; Galvan et al 2008; Nicholson & Kullmann, 2014). Several interneuron subtypes, predominantly in strata pyramidale and oriens, exhibit NMDAR independent LTP, which instead depends on both Ca2+-permeable AMPA receptors (CP-AMPARs) and group I metabotropic glutamate receptors (mGluRs) (Perez et al 2001; Lapointe et al 2004; Lamsa et al 2007; Oren et al 2009; Le Duigou & Kullmann, 2011; Roux et al 2013). Both CP-AMPARs and group I mGluRs are activated upon high-frequency stimulation of presynaptic glutamatergic axons. This ‘anti-Hebbian’ feature, contrasting with ‘Hebbian’ LTP in principal cells, can be explained by polyamine-dependent rectification of CP-AMPARs (Lamsa et al 2007; Oren et al 2009; Kullmann et al 2012)

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Conclusion