Academic literature on the topic 'Cellule amacrine starburst'

Cell-intrinsic factors, in conjunction with environmental signals, guide migration, differentiation, and connectivity during early development of neuronal circuits. Within the retina, inhibitory starburst amacrine cells (SBACs) comprise ON types with somas in the ganglion cell layer (GCL) and dendrites stratifying narrowly in the inner half of the inner plexiform layer (IPL) and OFF types with somas in the inner nuclear layer (INL) and dendrites stratifying narrowly in the outer half of the IPL. The transcription factor Sox2 is crucial to this subtype specification. Without Sox2, many ON-type SBACs destined for the GCL settle in the INL while many that reach the GCL develop bistratified dendritic arbors. This study asked whether ON-type SBACs in Sox2-conditional knockout retinas exhibit selective connectivity only with ON-type bipolar cells or their bistratified morphology allows them to connect to both ON and OFF bipolar cells. Physiological data demonstrate that these cells receive ON and OFF excitatory inputs, indicating that the ectopically stratified dendrites make functional synapses with bipolar cells. The excitatory inputs were smaller and more transient in Sox2-conditional knockout compared with wild type; however, inhibitory inputs appeared largely unchanged. Thus dendritic stratification, rather than cellular identification, may be the major factor that determines ON vs. OFF connectivity. NEW & NOTEWORTHY Conditional knockout of the transcription factor Sox2 during early embryogenesis converts a monostratifying starburst amacrine cell into a bistratifying starburst cell. Here we show that these bistratifying starburst amacrine cells form functional synaptic connections with both ON and OFF bipolar cells. This suggests that normal ON vs. OFF starburst connectivity may not require distinct molecular specification. Proximity alone may be sufficient to allow formation of functional synapses.

We have examined the role of neighbor relationships between cholinergic amacrine cells upon their positioning and dendritic field size by producing partial ablations of this population of cells during early development. We first determined the effectiveness ofl-glutamate as an excitotoxin for ablating cholinergic amacrine cells in the developing mouse retina. Subcutaneous injections (4 mg/g) made on P-3 and thereafter were found to produce a near-complete elimination, while injections at P-2 were ineffective. Lower doses on P-3 produced only partial reductions, and were subsequently used to examine the effect of partial ablation upon mosaic organization and dendritic growth of the remaining cells. Four different Voronoi-based measures of mosaic geometry were examined inl-glutamate-treated and normal (saline-treated) retinas. Partial depletions of around 40% produced cholinergic mosaics that, when scaled for density, approximated the mosaic geometry of the normal retina. Separate comparisons simulating a 40% random deletion of the normal retina produced mosaics that were no different from those experimentally depleted retinas. Consequently, no evidence was found for positional regulation in the absence of normal neighbor relationships. Single cells in the ganglion cell layer were intracellularly filled with Lucifer Yellow to examine the morphology and dendritic field extent following partial ablation of the cholinergic amacrine cells. No discernable effect was found on their starburst morphology, and total dendritic field area, number of primary dendrites, and branch frequency were not significantly different. Cholinergic amacrine cells normally increase their dendritic field area after P-3 in excess of retinal expansion; despite this, the present results show that this growth is not controlled by the density of neighboring processes.

Correlated spontaneous activity in the developing retina (termed “retinal waves”) plays an instructive role in refining neural circuits of the visual system. Depolarizing (ON) and hyperpolarizing (OFF) starburst amacrine cells (SACs) initiate and propagate cholinergic retinal waves. Where cholinergic retinal waves stop, SACs are thought to be driven by glutamatergic retinal waves initiated by ON-bipolar cells. However, the properties and function of cholinergic and glutamatergic waves in ON- and OFF-SACs still remain poorly understood. In the present work, we performed whole-cell patch-clamp recordings and Ca2+ imaging from genetically labeled ON- and OFF-SACs in mouse flat-mount retinas. We found that both SAC subtypes exhibited spontaneous rhythmic depolarization during cholinergic and glutamatergic waves. Interestingly, ON-SACs had wave-induced action potentials (APs) in an age-dependent manner, but OFF-SACs did not. Simultaneous Ca2+ imaging and patch-clamp recordings demonstrated that, during a cholinergic wave, APs of an ON-SAC appeared to promote the dendritic release of acetylcholine onto neighboring ON- and OFF-SACs, which enhances their Ca2+ transients. These results advance the understanding of the cellular mechanisms underlying correlated spontaneous activity in the developing retina.

A presynaptic neuron can increase its computational capacity by transmitting functionally distinct signals to each of its postsynaptic cell types. To determine whether such computational specialization occurs over fine spatial scales within a neurite arbor, we investigated computation at output synapses of the starburst amacrine cell (SAC), a critical component of the classical direction-selective (DS) circuit in the retina. The SAC is a non-spiking interneuron that co-releases GABA and acetylcholine and forms closely spaced (<5 μm) inhibitory synapses onto two postsynaptic cell types: DS ganglion cells (DSGCs) and neighboring SACs. During dynamic optogenetic stimulation of SACs in mouse retina, whole-cell recordings of inhibitory postsynaptic currents revealed that GABAergic synapses onto DSGCs exhibit stronger low-pass filtering than those onto neighboring SACs. Computational analyses suggest that this filtering difference can be explained primarily by presynaptic properties, rather than those of the postsynaptic cells per se. Consistent with functionally diverse SAC presynapses, blockade of N-type voltage-gated calcium channels abolished GABAergic currents in SACs but only moderately reduced GABAergic and cholinergic currents in DSGCs. These results jointly demonstrate how specialization of synaptic outputs could enhance parallel processing in a compact interneuron over fine spatial scales. Moreover, the distinct transmission kinetics of GABAergic SAC synapses are poised to support the functional diversity of inhibition within DS circuitry.

Direction selectivity represents an elementary sensory computation that can be related to underlying synaptic mechanisms. In mammalian retina, direction-selective ganglion cells (DSGCs) respond strongly to visual motion in a “preferred” direction and weakly to motion in the opposite, “null” direction. The DS mechanism depends on starburst amacrine cells (SACs), which provide null direction-tuned GABAergic inhibition and untuned cholinergic excitation to DSGCs. GABAergic inhibition depends on conventional synaptic transmission, whereas cholinergic excitation apparently depends on paracrine (i.e., non-synaptic) transmission. Despite its paracrine mode of transmission, cholinergic excitation is more transient than GABAergic inhibition, yielding a temporal difference that contributes essentially to the DS computation. To isolate synaptic mechanisms that generate the distinct temporal properties of cholinergic and GABAergic transmission from SACs to DSGCs, we optogenetically stimulated SACs while recording postsynaptic currents (PSCs) from DSGCs in mouse retina. Direct recordings from channelrhodopsin-2-expressing (ChR2+) SACs during quasi-white noise (WN) (0-30 Hz) photostimulation demonstrated precise, graded optogenetic control of SAC membrane current and potential. Linear systems analysis of ChR2-evoked PSCs recorded in DSGCs revealed cholinergic transmission to be faster than GABAergic transmission. A deconvolution-based analysis showed that distinct postsynaptic receptor kinetics fully account for the temporal difference between cholinergic and GABAergic transmission. Furthermore, GABAA receptor blockade prolonged cholinergic transmission, identifying a new functional role for GABAergic inhibition of SACs. Thus, fast cholinergic transmission from SACs to DSGCs arises from at least two distinct mechanisms, yielding temporal properties consistent with conventional synapses despite its paracrine nature.