| First Author | Zhang C | Year | 2014 |
| Journal | J Neurophysiol | Volume | 112 |
| Issue | 12 | Pages | 3125-37 |
| PubMed ID | 25231618 | Mgi Jnum | J:358751 |
| Mgi Id | MGI:6837578 | Doi | 10.1152/jn.00505.2014 |
| Citation | Zhang C, et al. (2014) Adeno-associated virus-RNAi of GlyRalpha1 and characterization of its synapse-specific inhibition in OFF alpha transient retinal ganglion cells. J Neurophysiol 112(12):3125-37 |
| abstractText | In the central nervous system, inhibition shapes neuronal excitation. In spinal cord glycinergic inhibition predominates, whereas GABAergic inhibition predominates in the brain. The retina uses GABA and glycine in approximately equal proportions. Glycinergic crossover inhibition, initiated in the On retinal pathway, controls glutamate release from presynaptic OFF cone bipolar cells (CBCs) and directly shapes temporal response properties of OFF retinal ganglion cells (RGCs). In the retina, four glycine receptor (GlyR) alpha-subunit isoforms are expressed in different sublaminae and their synaptic currents differ in decay kinetics. GlyRalpha1, expressed in both On and Off sublaminae of the inner plexiform layer, could be the glycinergic isoform that mediates On-to-Off crossover inhibition. However, subunit-selective glycine contributions remain unknown because we lack selective antagonists or cell class-specific subunit knockouts. To examine the role of GlyRalpha1 in direct inhibition in mature RGCs, we used retrogradely transported adeno-associated virus (AAV) that performed RNAi and eliminated almost all glycinergic spontaneous and visually evoked responses in PV5 (OFFalpha(Transient)) RGCs. Comparisons of responses in PV5 RGCs infected with AAV-scrambled-short hairpin RNA (shRNA) or AAV-Glra1-shRNA confirm a role for GlyRalpha1 in crossover inhibition in cone-driven circuits. Our results also define a role for direct GlyRalpha1 inhibition in setting the resting membrane potential of PV5 RGCs. The absence of GlyRalpha1 input unmasked a serial and a direct feedforward GABA(A)ergic modulation in PV5 RGCs, reflecting a complex interaction between glycinergic and GABA(A)ergic inhibition. |
