Dominick P. Purpura Department of Neuroscience, Albert Einstein College of Medicine, Bronx, NY 10461.
Dominick P. Purpura Department of Neuroscience, Albert Einstein College of Medicine, Bronx, NY 10461
eNeuro. 2021 Mar 11;8(2). doi: 10.1523/ENEURO.0450-20.2021. Print 2021 Mar-Apr.
In the hippocampus, the excitatory synapse between dentate granule cell (GC) axons, or mossy fibers (MFs), and CA3 pyramidal cells (MF-CA3) expresses robust forms of short-term plasticity, such as frequency facilitation and post-tetanic potentiation (PTP). These forms of plasticity are due to increases in presynaptic neurotransmitter release, and can be engaged when dentate GCs fire in bursts (e.g., during exploratory behaviors) and bring CA3 pyramidal neurons above threshold. While frequency facilitation at this synapse is limited by endogenous activation of presynaptic metabotropic glutamate receptors (mGluRs), whether MF-PTP can be regulated in an activity-dependent manner is unknown. Here, using physiologically relevant patterns of MF stimulation in acute mouse hippocampal slices, we found that disrupting postsynaptic Ca dynamics increases MF-PTP, strongly suggesting a form of Ca-dependent retrograde suppression of this form of plasticity. PTP suppression requires a few seconds of MF bursting activity and Ca release from internal stores. Our findings raise the possibility that the powerful MF-CA3 synapse can negatively regulate its own strength not only during PTP-inducing activity typical of normal exploratory behaviors, but also during epileptic activity.
在海马体中，齿状回颗粒细胞（GC）轴突或苔藓纤维（MFs）与 CA3 锥体神经元（MF-CA3）之间的兴奋性突触表现出强烈的短期可塑性形式，如频率易化和强直后增强（PTP）。这些形式的可塑性是由于突触前神经递质释放的增加引起的，当齿状回 GC 爆发式放电（例如，在探索行为期间）并使 CA3 锥体神经元超过阈值时，可以引发这些可塑性。虽然该突触的频率易化受到内源性激活的突触前代谢型谷氨酸受体（mGluRs）的限制，但 MF-PTP 是否可以以活动依赖性方式进行调节尚不清楚。在这里，我们使用急性小鼠海马切片中生理相关的 MF 刺激模式发现，破坏突触后 Ca 动力学会增加 MF-PTP，强烈表明存在一种 Ca 依赖性逆行抑制这种可塑性的形式。PTP 抑制需要几秒钟的 MF 爆发活动和内部储存的 Ca 释放。我们的发现提出了一种可能性，即强大的 MF-CA3 突触不仅可以在正常探索行为典型的诱导 PTP 活动期间，而且可以在癫痫活动期间，负向调节其自身强度。
