Department of Physiology and Kavli Institute For Fundamental Neuroscience, University of California San Francisco, San Francisco, California, United States.
Semel Institute for Neuroscience and Human Behavior, Department of Psychiatry and Biobehavioral Sciences, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, California, United States.
J Neurophysiol. 2024 Jul 1;132(1):34-44. doi: 10.1152/jn.00463.2023. Epub 2024 May 22.
When adult mice are repeatedly exposed to a particular visual stimulus for as little as 1 h per day for several days while their visual cortex (V1) is in the high-gain state produced by locomotion, that specific stimulus elicits much stronger responses in V1 neurons for the following several weeks, even when measured in anesthetized animals. Such stimulus-specific enhancement (SSE) is not seen if locomotion is prevented. The effect of locomotion on cortical responses is mediated by vasoactive intestinal peptide (VIP) positive interneurons, which can release both the peptide and the inhibitory neurotransmitter GABA. Previous studies have examined the role of VIP-ergic interneurons, but none have distinguished the individual roles of peptide from GABA release. Here, we used genetic ablation to determine which of those molecules secreted by VIP-ergic neurons is responsible for SSE. SSE was not impaired by VIP deletion but was prevented by compromising release of GABA from VIP cells. This finding suggests that SSE may result from Hebbian mechanisms that remain present in adult V1. Many neurons package and release a peptide along with a conventional neurotransmitter. The conventional view is that such peptides exert late, slow effects on plasticity. We studied a form of cortical plasticity that depends on the activity of neurons that express both vasoactive intestinal peptide (VIP) and the inhibitory neurotransmitter GABA. GABA release accounted for their action on plasticity, with no effect of deleting the peptide on this phenomenon.
当成年老鼠在其视觉皮层（V1）处于由运动产生的高增益状态时，每天只需暴露于特定视觉刺激 1 小时，连续几天，即使在麻醉动物中测量，该特定刺激也会在接下来的几周内引起 V1 神经元更强的反应。如果阻止运动，就不会出现这种刺激特异性增强（SSE）。运动对皮层反应的影响是由血管活性肠肽（VIP）阳性中间神经元介导的，这些神经元可以释放肽和抑制性神经递质 GABA。以前的研究已经检查了 VIP 能中间神经元的作用，但没有区分肽和 GABA 释放的个别作用。在这里，我们使用遗传消融来确定由 VIP 能神经元分泌的哪种分子负责 SSE。SSE 不受 VIP 删除的影响，但 VIP 细胞中 GABA 释放受到损害时会被阻止。这一发现表明，SSE 可能是由 Hebbian 机制引起的，这些机制在成年 V1 中仍然存在。许多神经元将肽与传统神经递质一起包装和释放。传统观点认为，这种肽对可塑性具有晚期、缓慢的影响。我们研究了一种依赖于表达血管活性肠肽（VIP）和抑制性神经递质 GABA 的神经元活性的皮层可塑性。GABA 释放解释了它们对可塑性的作用，删除肽对这种现象没有影响。
