Nicholson Elizabeth, Kullmann Dimitri M
University College London Institute of Neurology, London, UK.
J Physiol. 2017 Jun 1;595(11):3449-3458. doi: 10.1113/JP273695. Epub 2017 Mar 22.
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 Ca -permeable AMPA receptors and group I metabotropic glutamate receptors. We show that T-type Ca 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 Ca 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 Ca -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 Ca that contributes to synaptic plasticity. T-type Ca 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 Ca thus converge on NMDA receptor independent LTP induction in O/A interneurons.
海马体原层的规则发放中间神经元表现出一种兴奋性突触传递的长时程增强形式，该形式不依赖于NMDA受体，但需要Ca²⁺通透的AMPA受体和I组代谢型谷氨酸受体的共同激活。我们发现T型钙通道存在于此类中间神经元中。阻断T型电流可阻止长时程增强的诱导，并且还会干扰由突触后动作电位串或通过将突触后超极化与I组代谢型受体激活配对所诱导的持久增强。因此，几种钙源汇聚于NMDA受体非依赖性突触可塑性的诱导过程中。
海马体原层-齿状回（O/A）中间神经元中不依赖NMDA受体的长时程增强（LTP）需要突触后I组代谢型谷氨酸受体（mGluRs）和Ca²⁺通透的AMPA受体共同激活。此类AMPA受体的整流特性有助于在超极化电位下优先诱导LTP。当中间神经元超极化时，I组mGluRs的外源性激活，或者在没有突触前刺激的情况下通过突触后动作电位串，也可以触发兴奋性突触传递的持续增加。在本研究中，我们确定低阈值瞬态（T型）通道是有助于突触可塑性的另一种钙源。在小鼠规则发放的O/A中间神经元中检测到T型钙电流。药理学阻断T型电流可防止由谷氨酸能轴突高频刺激或应用I组mGluR激动剂二羟基苯甘氨酸并与突触后超极化配对所诱导的LTP。T型电流阻断还可防止由突触后动作电位串诱导的突触增强。因此，几种钙源汇聚于O/A中间神经元中不依赖NMDA受体的LTP诱导过程。
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