무축삭 세포(Amacrine Cell)
성화상 무축삭 세포(Starburst amacrine cells, SAC 또는 SBAC)는 이름이 보여주듯 수지상 가지(dendritic arbor)의 모양이 “별 모양의 광채(starburst)”를 닮은 특징에 의해 일차적으로 확인할 수 있는 망막의 무축삭 세포의 일종입니다. 성화상 무축삭 세포의 두 가지 중요한 역할이 밝혀진 바 있습니다. 성화상 무축삭 세포는 (1) 방향 선택성의 계산에 중요한 역할을 하며 또한 (2) 망막의 발생에 중요한 기능을 합니다. 다른 계층화, 형태, 연결 및 방향 선택성에서의 역할에 따라 명확하게 정의된 두 종류의 성화상 무축삭 세포들이 있습니다.bipolar cells, however, their tasks are often more specialized. Each type of amacrine cell connects with a particular type of bipolar cell, and generally has a particular type of neurotransmitter. For example, one such population, AII, 'piggybacks' rod bipolar cells onto the cone bipolar circuitry. It connects rod bipolar cell output with cone bipolar cell input, and from there the signal can travel to the respective ganglion cells.
Most are inhibitory using either GABA or glycine as neurotransmitters.
시각 반응 성질
일반적으로 말하면, 성화상 무축삭 세포는 세포체(soma, cell body)로부터 원거리의 수상돌기(dendrites)를 향해 움직이는 시각적 자극(원심성 또는CF운동)에만 반응을 하고 반대방향으로 움직이는 시각적 반응(구심성 또는 CP 운동)에는 반응을 하지 않습니다. 성화상 무축삭 세포의 이러한 성질은 2 광자 영상법에 의해 확립되었습니다. 아래의 그림은 성화상 무축삭 세포의 시각 반응을 도식화한 것을 보여주고 있습니다. (A) 원거리의 수상돌기에 빛을 쏘여 주었을 때의 반응. (B) 근거리에 빛을 반짝 쏘여주고 원거리에서 빛을 반짝 쏘여주어 원심성 운동을 흉내냈을 때의 반응. (C) 원거리에 빛을 쏘여주고 다시 더 먼 원거리에 빛을 쏘여주어 구심성 운동을 흉내냈을 때의 반응. 성화상 무축삭 세포는 원심성 방향의 운동에 가장 반응이 높다는 것에 주의를 기울여주십시오.
As detailed below, starburst amacrine cells (SAC) exhibit very selective visual response properties that have to do with a stimulus' direction with respect to the SAC's dendrites.
성화상 무축삭 세포는 망막의 세포 중 유일하게 두 종류의 신경전달물질을 내는 세포입니다. 이들 세포는 보통 억제성 신경전달물질인 GABA와 흥분성 신경전달물질인 아세틸콜린(Ach)을 분비합니다. 이들 신경전달물질의 분비는 단일시냅스성이며 칼슘에 의해 조절됩니다. 그러나 이들 두 가지 신경전달물질이 동시에 분비되지는 않는 다는 것 또한 알려져 있습니다. 이들 두 가지 신경전달물질의 분비 성질은 완충액의 변화, 특정 칼슘 억제제, 및 세포 외 농도에 의해 다르게 영향을 받게 됩니다.
Starburst amacrine cells exhibit very strange biophysics. Distinct SAC dendrites are selectively activated by visual stimuli moving centrifugally with respect to those distinct dendrites. SAC dendrite-specific direction selectivity is thought to underlie the direction selectivity of on/off direction-selective ganglion cells, but the mechanism by which this direction selectivity is generated in SAC dendrites remains unknown.
Amacrine cells have their cell bodies located in the inner nuclear layer of the retina and have projections in the inner plexiform layer. Different subtypes of amacrine cells project differently in the inner plexiform layer, as shown in the figure to the right depicting different types of narrow-field amacrine cells.
Amacrine cells send projections from their cell bodies into the inner plexiform layer. These projections arborize differently for different subtypes of amacrine cells. Amacrine cells have these projections distributed roughly circularly in the inner plexiform layer, though some subtypes arborize asymmetrically. Most amacrine cells can be classified according to the diameter of their projection arborization: "narrow-field" cells have arbors less than 125 µm in diameter, "medium-field" cell arbors range from 125 to 400 µm in diameter, and "wide-field" cell arbors are larger than 400 µm.
Their overall shapes alone are enough to serve as criterion for the classification.
Amacrine cells are postsynaptic targets of bipolar cells; these bipolar-to-amacrine cell synapses occur in the inner plexiform layer and are thought to be excitatory. Amacrine cells have their postsynaptic targets in the inner plexiform layer as well. Amacrine cell dendrites are known to synapse onto ganglion cell neurites in the IPL, mediating "antagonistic inputs from bipolar cells in the ganglion cell's surround."  These synapses are thought to be inhibitory.; this suggests that amacrine cells serve to regulate the output of bipolar cells in a negative-feedback loop fashion, and in fact it is thought that these amacrine-to-bipolar cell synapses are inhibitory. Further, "amacrine processes are also seen to contact other amacrine processes" in the IPL. These amacrine-to-amacrine cell synapses, interestingly enough, are thought to be excitatory. Amacrine cells are also known to form "reciprocal synapses" onto the bipolar cells that synapse onto them Thus, amacrine cells form synapses onto bipolar cells, ganglion cells, and other amacrine cells, all in the inner plexiform layer.
A few types of amacrine cells are associated with their respective functions and with corresponding ganglion cells. For example, starburst amacrine cells are known to make synapses onto on/off direction-selective ganglion cells (On/Off DSGCs) , and wide-field (WF) amacrine cells, also known as polyaxonal amacrine cells, are considered to be associated with object motion sensitive ganglion cells either directly or indirectly via bipolar cells .
There exist several molecular markers for amacrine cells, including Pax6, Tcfap2b, Gad1, and GlyT1. However, no markers exclusively expressed in amacrine cells are known to exist, and there exist "far fewer molecular markers [for amacrine cells] than known morphological types" of amacrine cells.
Antibodies against choline acetyltransferase (ChAT), the acetylcholine biosynthetic enzyme, are useful in staining amacrine cells in the retina, as it has been thought for some time that amacrine cells are the only cholinergic retinal neurons. However, at least one study has shown that there may exist cholinergic ganglion cells through staining against an alternative splice variant of ChAT mRNA in rat retina.
Staining the retina against tyrosine hydroxylase (TH), a key enzyme in the dopamine biosynthetic pathway, reveals the dopaminergic amacrine cells. It should be noted, though, that (nor)adrenergic cells also contain TH, and thus in order to isolate only dopaminergic cells, staining should also be carried out against dopamine β-hydroxylase and phenylethanolamine N-methyltransferase, enzymes found in the (nor)adrenaline biosynthetic pathways, but not in the dopamine pathway.
Most amacrine cells are inhibitory and secrete only GABA or glycine, though in total, amacrine cells as a class use eight different neurotransmitters, including acetylcholine, dopamine, and several neuropeptides, such as vasoactive intestinal peptide (VIP), substance P, and somatostatin. A particular class of amacrine cells—the starburst amacrine cell—has been found to be both cholinergic and GABAergic. According to retinal neuron expert Richard Masland, it appears that every amacrine cell is GABA- or glycinergic, with those amacrine cells that secrete other neurotransmitters secreting them concurrently with GABA or glycine.
The first characterization of amacrine cells is often attributed to Santiago Ramón y Cajal. Using the Golgi method of staining neurons, he first saw these cells in the avian retina in the late 1880s, naming them "amacrine" cells ("amacrine" meaning "without axon" in Greek). Though he was the first to call them amacrine cells, he built on the earlier work of J. Müller, who had previously described "spongioblasts" in the retina that were likely the very same cells Ramón y Cajal later named "amacrine."
Open questions/status/relevance to Eyewire
Though it is more or less well-established how inhibitory amacrine cells function, it is less clear what functions non-GABAergic/glycinergic amacrine cells have in the retina. In particular, it is not well understood for which functions starburst amacrine cells require acetylcholine secretion or how starburst amacrine cells might use both GABA and acetylcholine in concert to accomplish certain fucntions. Starburst amacrine cells also exhibit very curious biophysics in that any given individual SAC dendrite is selectively activated by visual stimuli centrifugal with respect to that particular dendrite. The mechanism for this selectivity remains unknown.
Also, as stated above, no amacrine cell-exclusive molecular markers are known to exist; the discovery of such a marker would be incredibly beneficial to further amacrine cell research.
Status/relevance to Eyewire
Thus far, dozens of starburst amacrine cells have been reconstructed through Eyewire, as well as at least one AII amacrine cell.
- Thomas Euler, Peter B. Detwiler & Winfried Denk (2002). Directionally selective calcium signals in dendrites of starburst amacrine cells Nature 418: 845-852
- M. A. MacNeil & R. H. Masland (1998) Extreme Diversity among Amacrine Cells: Implications for Function Neuron 20: 971-982
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