Department of Biology, University of Maryland, College Park, MD, 20742, USA.
Biological Sciences Graduate Program, University of Maryland, College Park, 20742, MD, USA.
Sci Rep. 2021 Feb 4;11(1):3163. doi: 10.1038/s41598-021-82679-2.
The development of GABAergic interneurons is important for the functional maturation of cortical circuits. After migrating into the cortex, GABAergic interneurons start to receive glutamatergic connections from cortical excitatory neurons and thus gradually become integrated into cortical circuits. These glutamatergic connections are mediated by glutamate receptors including AMPA and NMDA receptors and the ratio of AMPA to NMDA receptors decreases during development. Since previous studies have shown that retinal input can regulate the early development of connections along the visual pathway, we investigated if the maturation of glutamatergic inputs to GABAergic interneurons in the visual cortex requires retinal input. We mapped the spatial pattern of glutamatergic connections to layer 4 (L4) GABAergic interneurons in mouse visual cortex at around postnatal day (P) 16 by laser-scanning photostimulation and investigated the effect of binocular enucleations at P1/P2 on these patterns. Gad2-positive interneurons in enucleated animals showed an increased fraction of AMPAR-mediated input from L2/3 and a decreased fraction of input from L5/6. Parvalbumin-expressing (PV) interneurons showed similar changes in relative connectivity. NMDAR-only input was largely unchanged by enucleation. Our results show that retinal input sculpts the integration of interneurons into V1 circuits and suggest that the development of AMPAR- and NMDAR-only connections might be regulated differently.
γ-氨基丁酸能中间神经元的发育对于皮质回路的功能成熟很重要。在迁移到皮质后，γ-氨基丁酸能中间神经元开始接收来自皮质兴奋性神经元的谷氨酸能连接，从而逐渐整合到皮质回路中。这些谷氨酸能连接由谷氨酸受体介导，包括 AMPA 和 NMDA 受体，并且在发育过程中 AMPA 与 NMDA 受体的比例降低。由于先前的研究表明视网膜输入可以调节视觉通路上的早期连接发育，我们研究了视觉皮层中 GABA 能中间神经元的谷氨酸能输入的成熟是否需要视网膜输入。我们通过激光扫描光刺激在大约出生后第 16 天（P）时映射了小鼠视觉皮层中第 4 层（L4）GABA 能中间神经元的谷氨酸能连接的空间模式，并研究了 P1/P2 时双眼切除术对这些模式的影响。在被剥夺眼球的动物中， Gad2 阳性中间神经元显示出来自 L2/3 的 AMPAR 介导输入的比例增加，而来自 L5/6 的输入比例降低。表达 Parvalbumin 的（PV）中间神经元的相对连接也发生了类似的变化。NMDAR 仅输入受剥夺眼球的影响基本不变。我们的结果表明，视网膜输入塑造了中间神经元整合到 V1 回路中的方式，并表明 AMPAR 和 NMDAR 仅连接的发育可能受到不同的调节。
