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Silvia JH Park, Bart Gerard Borghuis, In-Jung Kim, Jonathan B Demb; Function and circuitry of VIP+ amacrine cells in the mouse retina. Invest. Ophthalmol. Vis. Sci. 2015;56(7 ):2614.
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© ARVO (1962-2015); The Authors (2016-present)
Amacrine cells comprise ~30-40 types, each of which influences a specific collection of bipolar cell terminals, ganglion cell dendrites and other amacrine cells. Here, we investigated a specific group of vasoactive intestinal polypeptide (VIP)-expressing (VIP+) amacrine cells to discover their structure, function and synaptic connections.
VIP+ cells were identified by 1) expressing tdTomato in VIP-ires-Cre x Ai14 mice; 2) delivering virus that expresses Cre-dependent yellow fluorescent protein (YFP) into VIP-ires-Cre eyes; and 3) expressing YFP/Channelrhodopsin-2 (ChR2) in VIP-ires-Cre x Ai32 mice. All mice are available from Jackson laboratory. VIP+ cells were targeted for whole-cell patch clamp recording and two-photon imaging in vitro. Cell morphology was analyzed in fixed tissue after labeling for choline acetyltransferase-positive (ChAT) processes in the inner plexiform layer (i.e., the two ‘ChAT bands’). VIP+ cell synaptic outputs were studied by activating ChR2 while recording from postsynaptic ganglion cells.
VIP+ cells comprise three primary types: a wide-field bistratified (WFB; ~400 μm-diameter) cell whose dendrites bracketed the ChAT bands; a narrow-field monostratified (NFM; ~180 μm) cell, whose dendrites were interposed between the ChAT bands; and a ganglion-cell-layer monostratified (GCLM; ~300 μm) cell, whose dendrites stratified between the inner ChAT band and the GCL. WFB cells received ON-OFF excitation and inhibition. In most cases, ON depolarization dominated. NFM cells received ON excitation and ON-OFF inhibition. Inhibitory currents were relatively large and generated ~20 mV hyperpolarizations at light OFF. GCLM cells received ON excitation and inhibition that drove ON depolarizations. With photoreceptor pathways blocked, ChR2 activation generated ~10 mV depolarizations in VIP+ cells. Three ganglion cell types received substantial GABAergic input from VIP+ cells: OFF Delta, W3 and ON-OFF Direction Selective, whereas two other types received weak and inconsistent input: ON and OFF Alpha.
Distinct morphological and physiological properties of GABAergic VIP+ amacrine cells predict specialized roles in specific retinal circuits. WFB cells could transmit cross-over inhibition from the ON to OFF pathway. NFM and GCLM cells could transmit feedforward inhibition to the ON pathway. Large hyperpolarizations in NFM cells suggest a possible role in disinhibition.
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