The function of wide-field amacrine cells in mammalian retina

The trophoblast glycoprotein (TPBG, aka oncofaeto protein, 5T4) is restrictively expressed in adult retina
in rod bipolar cell and the wide-field GABAergic ON/OFF amacrine cell, TH2-AC. Knocking out the Tpbg
gene in mice does not alter scotopic or photopic ERG responses but photopic contrast sensitivity was
enhanced, indicating that TPBG in TH2-AC participates in retinal information processing through
unidentified mechanism. We have found that TH2-AC intrinsic excitability is enhanced in the absence of
TPBG. We hypothesize that TPBG regulates TH2-AC excitability and that TH2-AC regulates retinal circuits
responsible for contrast and/or motion encoding. Given that amacrine cell is the most diverse but lthe
east understood retinal neuron thus far, studying TPBG in TH2-AC provides a rare opportunity to
understand how wide-field amacrine cell works in the mammalian retina. We will use mouse genetics
and electrophysiological approaches to 1) Use the DATIRESCre driver mouse line to manipulate TH2-AC to
understand the molecular and cellular basis of the enhanced photopic contrast sensitivity phenotype of
the Tpbg knockout animals (Aim-1) and 2) Genetically and/or virally ablate TH2-AC from retina to study
how retinal contrast and motion encoding are affected at the behavioral level by OKR and at the cellular
level in TH2-AC’s eight postsynaptic RGC partners (Aim-2). Completion of these independent aims will
lead to a better understanding on how a wide-field amacrine cell works in a mammalian retina.

Grant Number: 5R01EY034219-05
NIH Institute/Center: NIH
Principal Investigator: Ching-Kang Chen