Ferrer Camilo, Hsieh Helen, Wollmuth Lonnie P
Graduate Program in Neuroscience, Stony Brook University , Stony Brook, New York.
Department of Neurobiology & Behavior, Stony Brook University , Stony Brook, New York.
J Neurophysiol. 2018 Dec 1;120(6):3063-3076. doi: 10.1152/jn.00495.2018. Epub 2018 Oct 10.
Parvalbumin-expressing (PV) GABAergic interneurons regulate local circuit dynamics. In terms of the excitation driving PV interneuron activity, the N-methyl-d-aspartate receptor (NMDAR)-mediated component onto PV interneurons tends to be smaller than that onto pyramidal neurons but makes a significant contribution to their physiology and development. In the visual cortex, PV interneurons mature during the critical period. We hypothesize that during the critical period, the NMDAR-mediated signaling and functional properties of glutamatergic synapses onto PV interneurons are developmentally regulated. We therefore compared the α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR)- and NMDAR-mediated synaptic responses before (postnatal days 15-20, P15-P20), during (P25-P40), and after (P50-P60) the visual critical period. AMPAR miniature excitatory postsynaptic currents (mEPSCs) showed a developmental decrease in frequency, whereas NMDAR mEPSCs were absent or showed extremely low frequencies throughout development. For evoked responses, we consistently saw a NMDAR-mediated component, suggesting pre- or postsynaptic differences between evoked and spontaneous neurotransmission. Evoked responses showed input-specific developmental changes. For intralaminar inputs, the NMDAR-mediated component significantly decreased with development. This resulted in adult intralaminar inputs almost exclusively mediated by AMPARs, suited for the computation of synaptic inputs with precise timing, and likely having NMDAR-independent forms of plasticity. In contrast, interlaminar inputs maintained a stable NMDAR-mediated component throughout development but had a shift in the AMPAR paired-pulse ratio from depression to facilitation. Adult interlaminar inputs with facilitating AMPAR responses and a substantial NMDAR component would favor temporal integration of synaptic responses and could be modulated by NMDAR-dependent forms of plasticity. NEW & NOTEWORTHY We show for the first time input-specific developmental changes in the N-methyl-d-aspartate receptor component and short-term plasticity of the excitatory drive onto layers 2/3 parvalbumin-expressing (PV) interneurons in the visual cortex during the critical period. These developmental changes would lead to functionally distinct adult intralaminar and interlaminar glutamatergic inputs that would engage PV interneuron-mediated inhibition differently.
表达小白蛋白（PV）的γ-氨基丁酸能中间神经元调节局部回路动力学。就驱动PV中间神经元活动的兴奋性而言，作用于PV中间神经元的N-甲基-D-天冬氨酸受体（NMDAR）介导的成分往往小于作用于锥体神经元的成分，但对其生理和发育有重要贡献。在视觉皮层中，PV中间神经元在关键期成熟。我们假设在关键期，作用于PV中间神经元的谷氨酸能突触的NMDAR介导的信号传导和功能特性受到发育调控。因此，我们比较了视觉关键期之前（出生后第15 - 20天，P15 - P20）、期间（P25 - P40）和之后（P50 - P60）α-氨基-3-羟基-5-甲基-4-异恶唑丙酸受体（AMPAR）和NMDAR介导的突触反应。AMPAR微小兴奋性突触后电流（mEPSCs）的频率呈现发育性降低，而NMDAR mEPSCs在整个发育过程中不存在或频率极低。对于诱发反应，我们始终观察到一个NMDAR介导的成分，这表明诱发和自发神经传递在突触前或突触后存在差异。诱发反应显示出输入特异性的发育变化。对于层内输入，NMDAR介导的成分随着发育显著降低。这导致成年层内输入几乎完全由AMPAR介导，适合精确计时的突触输入计算，并且可能具有不依赖NMDAR的可塑性形式。相比之下，层间输入在整个发育过程中保持稳定的NMDAR介导成分，但AMPAR配对脉冲比率从抑制转变为易化。具有易化AMPAR反应和大量NMDAR成分的成年层间输入有利于突触反应的时间整合，并且可能受到依赖NMDAR的可塑性形式的调节。新发现与值得注意的是，我们首次展示了在关键期，视觉皮层中作用于第2/3层表达小白蛋白（PV）的中间神经元的兴奋性驱动的N-甲基-D-天冬氨酸受体成分和短期可塑性的输入特异性发育变化。这些发育变化将导致功能上不同的成年层内和层间谷氨酸能输入，它们将以不同方式参与PV中间神经元介导的抑制。
