Long-term potentiation in neurogliaform interneurons modulates excitation-inhibition balance in the temporoammonic pathway.
Long-term potentiation in neurogliaform interneurons modulates excitation-inhibition balance in the temporoammonic pathway.
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DOI：
10.1113/jp282753
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发表时间：
2022-09
影响因子：
5.5
通讯作者：
Kullmann, Dimitri M.
中科院分区：
文献类型：
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作者：
Mercier, Marion S.;Magloire, Vincent;Cornford, Jonathan H.;Kullmann, Dimitri M.
锥体神经元的顶端树突整合来自高级皮层和丘脑的信息，并在近端突触处控制信号传导和可塑性。在海马中，位于腔隙分子层（SLM）内的神经胶质细胞和其他中间神经元介导对CA 1锥体神经元远端树突的强烈抑制。这种抑制的募集本身是否受到使用依赖性可塑性的影响？如果是的话，适用什么样的诱导规则？在这里，我们发现小鼠SLM中的中间神经元表现出Hebbian NMDA受体依赖性长时程增强（LTP）。这种可塑性可以通过选择性光遗传学刺激来自内嗅皮层（EC）的颞氨通路中的传入神经来诱导，但不能通过来自丘脑连合核的传入神经的等效刺激来诱导。我们进一步表明，传入放电的θ爆发模式诱导神经胶质样中间神经元中的LTP，这些中间神经元使用神经元源性神经营养因子（NdNF）-Cre小鼠鉴定。EC传入的Theta爆发活动导致CA 1锥体神经元的双突触前馈抑制增加，但不是单突触兴奋。因此，SLM中间神经元的活性依赖性突触可塑性改变了锥体神经元顶树突EC输入的兴奋-抑制平衡，这意味着这些中间神经元在门控CA 1树突计算中的动态作用。 海马主要神经元远端树突中的生电现象在近端树突上的传入突触的突触可塑性门控中起主要作用。顶端树突也接受强大的前馈抑制，在很大程度上由神经胶质样神经元介导。在这里，我们发现，来自内嗅皮层（EC）的传入神经中的θ波爆发活动在招募这些GABA能细胞的兴奋性突触处诱导了“赫布”长时程增强（LTP）。支配顶树突的中间神经元中的LTP增加了主神经元的双突触抑制，从而改变了颞氨（TA）通路中的兴奋-抑制平衡，有利于抑制，这对近端树突中的计算和学习规则具有影响。 Hebbian长时程增强（LTP）兴奋性传递到位于海马腔隙分子层（SLM）内的中间神经元上，可以通过涉及突触前和突触后活动配对的电刺激方案诱导。使用Ndnf-Cre小鼠，我们发现海马神经胶质样（NGF）细胞表达这种形式的LTP。这些细胞接收来自丘脑和内嗅皮层（EC）的核reuniens的LTP传入，但选择性的光遗传激活的任一组纤维揭示LTP仅在EC输入。使用光遗传学theta-burst刺激（OptoTBS）方案以生理相关的方式刺激EC纤维，我们表明NGF中间神经元LTP转化为对CA 1锥体细胞远端树突的双突触抑制的增加。单突触EC-CA 1锥体细胞输入不经历等效的增强，导致该通路的兴奋/抑制（E/I）比净减少。
Apical dendrites of pyramidal neurons integrate information from higher‐order cortex and thalamus, and gate signalling and plasticity at proximal synapses. In the hippocampus, neurogliaform cells and other interneurons located within stratum lacunosum‐moleculare (SLM) mediate powerful inhibition of CA1 pyramidal neuron distal dendrites. Is the recruitment of such inhibition itself subject to use‐dependent plasticity, and if so, what induction rules apply? Here we show that interneurons in mouse SLM exhibit Hebbian NMDA receptor‐dependent long‐term potentiation (LTP). Such plasticity can be induced by selective optogenetic stimulation of afferents in the temporoammonic pathway from the entorhinal cortex (EC), but not by equivalent stimulation of afferents from the thalamic nucleus reuniens. We further show that theta‐burst patterns of afferent firing induces LTP in neurogliaform interneurons identified using neuron‐derived neurotrophic factor (Ndnf)‐Cre mice. Theta‐burst activity of EC afferents led to an increase in disynaptic feed‐forward inhibition, but not monosynaptic excitation, of CA1 pyramidal neurons. Activity‐dependent synaptic plasticity in SLM interneurons thus alters the excitation–inhibition balance at EC inputs to the apical dendrites of pyramidal neurons, implying a dynamic role for these interneurons in gating CA1 dendritic computations. Electrogenic phenomena in distal dendrites of principal neurons in the hippocampus have a major role in gating synaptic plasticity at afferent synapses on proximal dendrites. Apical dendrites also receive powerful feed‐forward inhibition, mediated in large part by neurogliaform neurons. Here we show that theta‐burst activity in afferents from the entorhinal cortex (EC) induces ‘Hebbian’ long‐term potentiation (LTP) at excitatory synapses recruiting these GABAergic cells. LTP in interneurons innervating apical dendrites increases disynaptic inhibition of principal neurons, thus shifting the excitation–inhibition balance in the temporoammonic (TA) pathway in favour of inhibition, with implications for computations and learning rules in proximal dendrites. Abstract figure legend Hebbian long‐term potentiation (LTP) of excitatory transmission onto interneurons located within hippocampal stratum lacunosum‐moleculare (SLM) can be induced by electrical stimulation protocols involving pairing of pre‐ and postsynaptic activity. Using Ndnf‐Cre mice, we show that hippocampal neurogliaform (NGF) cells express this form of LTP. These cells receive glutamatergic afferents from both the nucleus reuniens of the thalamus and the entorhinal cortex (EC), but selective optogenetic activation of either set of fibres reveals LTP at EC inputs only. Using an optogenetic theta‐burst stimulation (OptoTBS) protocol to stimulate EC fibres in a physiologically relevant way, we show that NGF interneuron LTP translates to an increase in disynaptic inhibition onto CA1 pyramidal cell distal dendrites. Monosynaptic EC–CA1 pyramidal cell inputs do not undergo equivalent potentiation, leading to a net decrease in the excitation/inhibition (E/I) ratio of this pathway.