TY - JOUR
T1 - Developmental Regulation and Activity-Dependent Maintenance of GABAergic Presynaptic Inhibition onto Rod Bipolar Cell Axonal Terminals
AU - Schubert, Timm
AU - Hoon, Mrinalini
AU - Euler, Thomas
AU - Lukasiewicz, Peter D.
AU - Wong, Rachel O.L.
N1 - Funding Information:
This work was supported by the National Institutes of Health (EY10699 to R.O.W., EY08922 to P.D.L., EY02687 to the Department of Ophthalmology, Washington University and EY01730 to the Department of Ophthalmology, University of Washington), Research to Prevent Blindness (to P.D.L.), and Deutsche Forschungsgemeinschaft (SCHU2243/1-1 to T.S and EXC 307 to T.E.). We thank A. Barria and W. Cerpa for help with western blots and E. Parker for assistance with electron microscopy. We are grateful to R. Sinha, H. Okawa, and L. Della Santina for helpful comments on the manuscript.
PY - 2013/4/10
Y1 - 2013/4/10
N2 - Presynaptic inhibition onto axons regulates neuronal output, but how such inhibitory synapses develop and are maintained in vivo remains unclear. Axon terminals of glutamatergic retinal rod bipolar cells (RBCs) receive GABAA and GABAC receptor-mediated synaptic inhibition. We found that perturbing GABAergic or glutamatergic neurotransmission does not prevent GABAergic synaptogenesis onto RBC axons. But, GABA release is necessary for maintaining axonal GABA receptors. This activity-dependent process is receptor subtype specific: GABAC receptors are maintained, whereas GABAA receptors containing α1, but not α3, subunits decrease over time in mice with deficient GABA synthesis. GABAA receptor distribution on RBC axons is unaffected in GABAC receptor knockout mice. Thus, GABAA and GABAC receptor maintenance are regulated separately. Although immature RBCs elevate their glutamate release when GABA synthesis is impaired, homeostatic mechanisms ensure that the RBC output operates within its normal range after eye opening, perhaps to regain proper visual processing within the scotopic pathway
AB - Presynaptic inhibition onto axons regulates neuronal output, but how such inhibitory synapses develop and are maintained in vivo remains unclear. Axon terminals of glutamatergic retinal rod bipolar cells (RBCs) receive GABAA and GABAC receptor-mediated synaptic inhibition. We found that perturbing GABAergic or glutamatergic neurotransmission does not prevent GABAergic synaptogenesis onto RBC axons. But, GABA release is necessary for maintaining axonal GABA receptors. This activity-dependent process is receptor subtype specific: GABAC receptors are maintained, whereas GABAA receptors containing α1, but not α3, subunits decrease over time in mice with deficient GABA synthesis. GABAA receptor distribution on RBC axons is unaffected in GABAC receptor knockout mice. Thus, GABAA and GABAC receptor maintenance are regulated separately. Although immature RBCs elevate their glutamate release when GABA synthesis is impaired, homeostatic mechanisms ensure that the RBC output operates within its normal range after eye opening, perhaps to regain proper visual processing within the scotopic pathway
UR - http://www.scopus.com/inward/record.url?scp=84876071902&partnerID=8YFLogxK
U2 - 10.1016/j.neuron.2013.01.037
DO - 10.1016/j.neuron.2013.01.037
M3 - Article
C2 - 23583111
AN - SCOPUS:84876071902
SN - 0896-6273
VL - 78
SP - 124
EP - 137
JO - Neuron
JF - Neuron
IS - 1
ER -