PT  - JOURNAL ARTICLE
AU  - William N. Grimes
AU  - Didem Göz Aytürk
AU  - Mrinalini Hoon
AU  - Takeshi Yoshimatsu
AU  - Clare Gamlin
AU  - Daniel Carrera
AU  - Amurta Nath
AU  - Francisco M. Nadal-Nicolás
AU  - Richard M. Ahlquist
AU  - Adit Sabnis
AU  - David M. Berson
AU  - Jeffrey S. Diamond
AU  - Rachel O. Wong
AU  - Connie Cepko
AU  - Fred Rieke
TI  - A high-density narrow-field inhibitory retinal interneuron with direct coupling to Müller glia
AID  - 10.1523/JNEUROSCI.0199-20.2021
DP  - 2021 Jun 03
TA  - The Journal of Neuroscience
PG  - JN-RM-0199-20
4099  - http://www.jneurosci.org/content/early/2021/06/01/JNEUROSCI.0199-20.2021.short
4100  - http://www.jneurosci.org/content/early/2021/06/01/JNEUROSCI.0199-20.2021.full
AB  - 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 labelling 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 (dLGN) showed selective connections between MACs and a subpopulation of RGC 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.Significance Statement: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.