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

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.

Abstract: 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.