|
SignificanceNeuronal output is modulated by inhibition onto axons and dendrites by diverse inhibitory synapses comprising distinct receptor subunits. Factors that regulate the in vivo maturation of these synapses across cell-compartments are not well understood. We discovered that axonal GABAA receptors are down-regulated whereas dendritic GABAA receptors are up-regulated on retinal bipolar cells in the absence of vesicular GABA release. Deleting the {gamma}2 subunit of GABAA receptors specifically in bipolar cells only alters axonal GABAA receptor expression, suggesting that axonal and dendritic GABAA receptors have distinct subunit compositions that are regulated independently. Moreover, vesicular GABA release from presynaptic amacrine but not horizontal interneurons is important. Thus, regulation of inhibitory synapse maturation across the bipolar cell is input-type, receptor-type, and cell-compartment-type specific. Neuronal output is modulated by inhibition onto both dendrites and axons. It is unknown whether inhibitory synapses at these two cellular compartments of an individual neuron are regulated coordinately or separately during in vivo development. Because neurotransmission influences synapse maturation and circuit development, we determined how loss of inhibition affects the expression of diverse types of inhibitory receptors on the axon and dendrites of mouse retinal bipolar cells. We found that axonal GABA but not glycine receptor expression depends on neurotransmission. Importantly, axonal and dendritic GABAA receptors comprise distinct subunit compositions that are regulated differentially by GABA release: Axonal GABAA receptors are down-regulated but dendritic receptors are up-regulated in the absence of inhibition. The homeostatic increase in GABAA receptors on bipolar cell dendrites is pathway-specific: Cone but not rod bipolar cell dendrites maintain an up-regulation of receptors in the transmission deficient mutants. Furthermore, the bipolar cell GABAA receptor alterations are a consequence of impaired vesicular GABA release from amacrine but not horizontal interneurons. Thus, inhibitory neurotransmission regulates in vivo postsynaptic maturation of inhibitory synapses with contrasting modes of action specific to synapse type and location.
|
