Department of Synapse and Network Development, Netherlands Institute for Neuroscience, 1105 BA Amsterdam, the Netherlands.
Max Planck Institute for Brain Research, Computation in Neural Circuits, 60438 Frankfurt am Main, Germany; TUM School of Life Sciences, Technical University of Munich, 85354 Freising, Germany.
Curr Biol. 2021 Jan 25;31(2):322-333.e5. doi: 10.1016/j.cub.2020.10.028. Epub 2020 Nov 5.
Spontaneous network activity shapes emerging neuronal circuits during early brain development prior to sensory perception. However, how neuromodulation influences this activity is not fully understood. Here, we report that the neuromodulator oxytocin differentially shapes spontaneous activity patterns across sensory cortices. In vivo, oxytocin strongly decreased the frequency and pairwise correlations of spontaneous activity events in the primary visual cortex (V1), but it did not affect the frequency of spontaneous network events in the somatosensory cortex (S1). Patch-clamp recordings in slices and RNAscope showed that oxytocin affects S1 excitatory and inhibitory neurons similarly, whereas in V1, oxytocin targets only inhibitory neurons. Somatostatin-positive (SST) interneurons expressed the oxytocin receptor and were activated by oxytocin in V1. Accordingly, pharmacogenetic silencing of V1 SST interneurons fully blocked oxytocin's effect on inhibition in vitro as well its effect on spontaneous activity patterns in vivo. Thus, oxytocin decreases the excitatory/inhibitory (E/I) ratio by recruiting SST interneurons and modulates specific features of V1 spontaneous activity patterns that are crucial for the wiring and refining of developing sensory circuits.
在感觉感知之前的早期大脑发育过程中,自发性网络活动塑造了新兴的神经元回路。然而,神经调质如何影响这种活动还不完全清楚。在这里,我们报告说,神经调质催产素在不同的感觉皮层中差异地塑造了自发性活动模式。在体内,催产素强烈降低了初级视觉皮层(V1)中自发性活动事件的频率和成对相关性,但它不影响躯体感觉皮层(S1)中自发性网络事件的频率。在切片中的膜片钳记录和 RNAscope 显示,催产素对 S1 兴奋性和抑制性神经元的影响相似,而在 V1 中,催产素仅靶向抑制性神经元。生长抑素阳性(SST)中间神经元表达催产素受体,并在 V1 中被催产素激活。因此,V1 SST 中间神经元的药理学基因沉默完全阻断了催产素在体外对抑制的作用,以及其对体内自发性活动模式的作用。因此,催产素通过募集 SST 中间神经元来降低兴奋/抑制(E/I)比,并调节 V1 自发性活动模式的特定特征,这些特征对于发育中的感觉回路的布线和细化至关重要。