Grimes William N, Aytürk Didem Göz, Hoon Mrinalini, Yoshimatsu Takeshi, Gamlin Clare, Carrera Daniel, Nath Amurta, Nadal-Nicolás Francisco M, Ahlquist Richard M, Sabnis Adit, Berson David M, Diamond Jeffrey S, Wong Rachel O, Cepko Connie, Rieke Fred
Department of Physiology and Biophysics, University of Washington, Seattle, Washington 98195
National Institute of Neurological Disease and Stroke, National Institutes of Health, Bethesda, Maryland 20892.
J Neurosci. 2021 Jul 14;41(28):6018-6037. doi: 10.1523/JNEUROSCI.0199-20.2021.
Amacrine cells are interneurons composing the most diverse cell class in the mammalian retina. They help encode visual features, such as edges or directed motion, by mediating excitatory and inhibitory interactions between input (i.e., bipolar) and output (i.e., ganglion) neurons in the inner plexiform layer (IPL). Like other brain regions, the retina also contains glial cells that contribute to neurotransmitter uptake, metabolic regulation, and neurovascular control. Here, we report that, in mouse retina (of either sex), an abundant, though previously unstudied inhibitory amacrine cell is coupled directly to Müller glia. Electron microscopic reconstructions of this amacrine type revealed chemical synapses with known retinal cell types and extensive associations with Müller glia, the processes of which often completely ensheathe the neurites of this amacrine cell. Microinjecting small tracer molecules into the somas of these amacrine cells led to selective labeling of nearby Müller glia, leading us to suggest the name "Müller glia-coupled amacrine cell," or MAC. Our data also indicate that MACs release glycine at conventional chemical synapses, and viral retrograde transsynaptic tracing from the dorsal lateral geniculate nucleus showed selective connections between MACs and a subpopulation of retinal ganglion cell types. Visually evoked responses revealed a strong preference for light increments; these "ON" responses were primarily mediated by excitatory chemical synaptic input and direct electrical coupling with other cells. This initial characterization of the MAC provides the first evidence for neuron-glia coupling in the mammalian retina and identifies the MAC as a potential link between inhibitory processing and glial function. Gap junctions between pairs of neurons or glial cells are commonly found throughout the nervous system and play multiple roles, including electrical coupling and metabolic exchange. In contrast, gap junctions between neurons and glia cells have rarely been reported and are poorly understood. Here we report the first evidence for neuron-glia coupling in the mammalian retina, specifically between an abundant (but previously unstudied) inhibitory interneuron and Müller glia. Moreover, viral tracing, optogenetics, and serial electron microscopy provide new information about the neuron's synaptic partners and physiological responses.
无长突细胞是中间神经元，构成哺乳动物视网膜中最多样化的细胞类型。它们通过介导内网状层（IPL）中输入（即双极）神经元和输出（即神经节）神经元之间的兴奋性和抑制性相互作用，帮助编码视觉特征，如边缘或定向运动。与其他脑区一样，视网膜中也含有神经胶质细胞，这些细胞有助于神经递质摄取、代谢调节和神经血管控制。在此，我们报告，在小鼠视网膜（无论雌雄）中，一种数量丰富但此前未被研究的抑制性无长突细胞直接与米勒胶质细胞相连。对这种无长突细胞类型的电子显微镜重建显示，它与已知的视网膜细胞类型存在化学突触，并与米勒胶质细胞有广泛联系，米勒胶质细胞的突起常常完全包裹住这种无长突细胞的神经突。向这些无长突细胞的胞体中微量注射小的示踪分子，导致附近的米勒胶质细胞被选择性标记，这使我们建议将其命名为“米勒胶质细胞耦合无长突细胞”，即MAC。我们的数据还表明，MAC在传统化学突触处释放甘氨酸，并且从背侧外侧膝状体核进行的病毒逆行跨突触示踪显示，MAC与一部分视网膜神经节细胞类型之间存在选择性连接。视觉诱发反应显示出对光增强有强烈偏好；这些“ON”反应主要由兴奋性化学突触输入和与其他细胞的直接电耦合介导。对MAC的这一初步特征描述为哺乳动物视网膜中的神经元 - 胶质细胞耦合提供了首个证据，并将MAC确定为抑制性处理与胶质细胞功能之间的潜在联系。神经元对或胶质细胞对之间的缝隙连接在整个神经系统中普遍存在，并发挥多种作用，包括电耦合和代谢交换。相比之下，神经元与胶质细胞之间的缝隙连接很少被报道，且了解甚少。在此我们报告了哺乳动物视网膜中神经元 - 胶质细胞耦合的首个证据，具体是在一种数量丰富（但此前未被研究）的抑制性中间神经元与米勒胶质细胞之间。此外，病毒示踪、光遗传学和连续电子显微镜提供了有关该神经元的突触伙伴和生理反应的新信息。
