Sanderson Thomas M, Ralph Liam T, Amici Mascia, Ng Ai Na, Kaang Bong-Kiun, Zhuo Min, Kim Sang Jeong, Georgiou John, Collingridge Graham L
Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, Sinai Health System, Toronto, ON, Canada.
Department of Brain and Cognitive Sciences, College of Natural Sciences, Seoul National University, Seoul, South Korea.
Front Synaptic Neurosci. 2022 May 9;14:857675. doi: 10.3389/fnsyn.2022.857675. eCollection 2022.
In area CA1 of the hippocampus, long-term depression (LTD) can be induced by activating group I metabotropic glutamate receptors (mGluRs), with the selective agonist DHPG. There is evidence that mGluR-LTD can be expressed by either a decrease in the probability of neurotransmitter release [P(r)] or by a change in postsynaptic AMPA receptor number. However, what determines the locus of expression is unknown. We investigated the expression mechanisms of mGluR-LTD using either a low (30 μM) or a high (100 μM) concentration of (RS)-DHPG. We found that 30 μM DHPG generated presynaptic LTD that required the co-activation of NMDA receptors, whereas 100 μM DHPG resulted in postsynaptic LTD that was independent of the activation of NMDA receptors. We found that both forms of LTD occur at the same synapses and that these may constitute the population with the lowest basal P(r). Our results reveal an unexpected complexity to mGluR-mediated synaptic plasticity in the hippocampus.
在海马体的CA1区域，通过使用选择性激动剂二氢-L-谷氨酸（DHPG）激活I组代谢型谷氨酸受体（mGluRs），可诱导长时程抑制（LTD）。有证据表明，mGluR-LTD可通过神经递质释放概率[P(r)]的降低或突触后AMPA受体数量的变化来表达。然而，决定表达位点的因素尚不清楚。我们使用低浓度（30μM）或高浓度（100μM）的（RS）-DHPG研究了mGluR-LTD的表达机制。我们发现，30μM的DHPG产生突触前LTD，这需要NMDA受体的共同激活，而100μM的DHPG导致突触后LTD，其独立于NMDA受体的激活。我们发现两种形式的LTD都发生在相同的突触处，并且这些突触可能构成基础P(r)最低的群体。我们的结果揭示了海马体中mGluR介导的突触可塑性存在意想不到的复杂性。
