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

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. AbstractNMDA 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.

NMDA receptor‐independent long‐term potentiation in hippocampal interneurons

“…In the present study, Nicholson and Kullmann () clearly showed that NMDA receptor‐independent LTP induced by high‐frequency stimulation of afferent fibres in the presence of the NMDA receptor antagonist d ‐2‐amino‐5‐phosphonovaleric acid ( d ‐APV) in O/A interneurons paired with postsynaptic hyperpolarization was almost completely inhibited by T‐type Ca 2+ channel blockers, indicating that the Ca 2+ influx through T‐type Ca 2+ channels is another source of Ca 2+ required for LTP induction. It is known whether this type of Ca 2+ channels is abundantly expressed in hippocampal interneurons, and in fact, the authors explicitly demonstrated electrophysiologically that T‐type Ca 2+ channels were functional in O/A interneurons.…”

“…In a previous paper by the same group (Le Duigou & Kullmann, 2011), exogenous activation of group I mGluRs with postsynaptic hyperpolarization was shown to be sufficient to induce LTP in the absence of presynaptic activities in hippocampal interneurons. This finding is rather unexpected because it is unclear why hyperpolarization in addition to mGluR activation is required for this type of LTP.In the present study, Nicholson and Kullmann (2017) clearly showed that NMDA receptor-independent LTP induced by high-frequency stimulation of afferent fibres in the presence of the NMDA receptor antagonist D-2-amino-5-phosphonovaleric acid (D-APV) in O/A interneurons paired with postsynaptic hyperpolarization was almost completely inhibited by T-type Ca 2+ channel blockers, indicating that the Ca 2+ influx through T-type Ca 2+ channels is another source of Ca 2+ required for LTP induction. It is known whether this type of Ca 2+ channels is abundantly expressed in hippocampal interneurons, and in fact, the authors explicitly demonstrated electrophysiologically that T-type Ca 2+ channels were functional in O/A interneurons.…”

“…Although the properties of depolarizing pulse‐induced potentiation have been extensively examined and key molecules associated with the potentiation have been identified in CA1 pyramidal cells, it has not been well known whether similar phenomena are observed in interneurons. In this issue of The Journal of Physiology , Nicholson and Kullmann () demonstrate that the T‐type Ca 2+ channel plays a pivotal role in the induction of a similar type of LTP in hippocampal stratum oriens‐alveus (O/A) interneurons. In a previous paper by the same group (Le Duigou & Kullmann, ), exogenous activation of group I mGluRs with postsynaptic hyperpolarization was shown to be sufficient to induce LTP in the absence of presynaptic activities in hippocampal interneurons.…”

Degeneracy in hippocampal physiology and plasticity

“…Specifically, there are strong lines of evidence that the induction of bidirectional synaptic plasticity in the hippocampus is mediated by different calcium sources, with certain protocols requiring synergistic activation of multiple calcium sources (Brager & Johnston, ; Christie et al, ; Golding et al, ; Huber et al, ; Nishiyama, Hong, Mikoshiba, Poo, & Kato, ; Raymond, ). These studies show that plasticity induction is dependent on influx of calcium through NMDA receptors (Christie et al, ; Collingridge & Bliss, ; Collingridge, Kehl, & McLennan, ; Morris, Anderson, Lynch, & Baudry, ; Mulkey & Malenka, ; Nishiyama et al, ; Tsien, Huerta, & Tonegawa, ; Wang, Xu, Wu, Duan, & Poo, ), voltage‐gated calcium channels (Brager & Johnston, ; Christie et al, ; Christie, Schexnayder, & Johnston, ; Johnston, Williams, Jaffe, & Gray, ; Moosmang et al, ; Nicholson & Kullmann, ; Wang et al, ), store‐operated calcium channels (Baba et al, ; Garcia‐Alvarez et al, ; Majewski & Kuznicki, ; Majewski et al, ; Prakriya & Lewis, ) and receptors on the ER activated by metabotropic receptors on the plasma membrane (Huber et al, ; Jedlicka & Deller, ; Nishiyama et al, ; Padamsey, Foster, & Emptage, ; Verkhratsky, ). Additionally, voltage‐gated channels and their auxiliary subunits (Anirudhan & Narayanan, ; Brager, Lewis, Chetkovich, & Johnston, ; Chen et al, ; Chung, Ge, et al, ; Chung, Qian, et al, ; Johnston et al, ; Jung, Kim, & Hoffman, ; Kim et al, ; Lin et al, ; Lujan et al, ; Malik & Johnston, ; Nolan et al, ; Sehgal et al, ; Shah et al, ; Watanabe, Hoffman, Migliore, & Johnston, ) have also been shown to critically regulate the strength and direction of synaptic plasticity.…”

Degeneracy in hippocampal physiology and plasticity

“…Specifically, there are strong lines of evidence that the induction of bidirectional synaptic plasticity in the hippocampus is mediated by different calcium sources, with certain protocols requiring synergistic activation of multiple calcium 16, 2017; sources (Brager and Johnston, 2007;Christie et al, 1996;Golding et al, 2002;Huber et al, 1995;Nishiyama et al, 2000;Raymond, 2007). These studies show that plasticity induction is dependent on influx of calcium through NMDA receptors (Christie et al, 1996;Collingridge and Bliss, 1987;Collingridge et al, 1983;Morris et al, 1986;Mulkey and Malenka, 1992;Nishiyama et al, 2000;Tsien et al, 1996;Wang et al, 2003), voltage-gated calcium channels (Brager and Johnston, 2007;Christie et al, 1996;Christie et al, 1997;Johnston et al, 1992;Moosmang et al, 2005;Nicholson and Kullmann, 2017;Wang et al, 2003), store-operated calcium channels (Baba et al, 2003;Garcia-Alvarez et al, 2015;Majewski and Kuznicki, 2015;Majewski et al, 2016;Prakriya and Lewis, 2015) and receptors on the ER activated by metabotropic receptors on the plasma membrane (Huber et al, 2000;Nishiyama et al, 2000;Verkhratsky, 2002). Additionally, voltage-gated channels and their auxiliary subunits (Anirudhan and Narayanan, 2015;Brager et al, 2013;Chen et al, 2006;Chung et al, 2009a;Chung et al, 2009b;Johnston et al,...…”