Abstract
Output signals of neural circuits, including the retina, are shaped by a combination of excitatory and inhibitory signals. Inhibitory signals can act presynaptically on axon terminals to control neurotransmitter release and regulate circuit function. However, it has been difficult to study the role of presynaptic inhibition in most neural circuits due to lack of cell type-specific and receptor type-specific perturbations. In this study, we used a transgenic approach to selectively eliminate GABAA inhibitory receptors from select types of second-order neurons - bipolar cells - in mouse retina and examined how this affects the light response properties of the well-characterized ON alpha ganglion cell retinal circuit. Selective loss of GABAA receptor-mediated presynaptic inhibition causes an enhanced sensitivity and slower kinetics of light-evoked responses from ON alpha ganglion cells thus highlighting the role of presynaptic inhibition in gain control and temporal filtering of sensory signals in a key neural circuit in the mammalian retina.
Highlights
A common motif by which inhibition acts in neural circuits is at the axon terminals of presynaptic neurons where it regulates synaptic release and controls the input-output relationship of a neural circuit (Fink et al, 2014; MacDermott et al, 1999)
We have taken advantage of a previously used (Hoon et al, 2015) transgenic manipulation in mouse retina that selectively eliminates a specific population of inhibitory receptors – GABAA receptors – from the axon terminals of defined types of presynaptic neurons – rod bipolar cells (RBCs) and Type 6 (T6) cone bipolar cell (CBC) – and determined its impact on the light-evoked response properties of one of the well characterized downstream retinal output neuron – the ON sustained alpha ganglion cell (GC) (ONa GC)
We show that GABAA receptor-mediated presynaptic inhibition is crucial for regulating the amplitude and contrast sensitivity of both rod and cone-driven signals routed to the ONa GCs
Summary
A common motif by which inhibition acts in neural circuits is at the axon terminals of presynaptic neurons where it regulates synaptic release and controls the input-output relationship of a neural circuit (Fink et al, 2014; MacDermott et al, 1999). Immunolabeling against the dominant subunit of GABAA receptors shows a dense expression, not specific to a single cell class but localized throughout the retinal synaptic layer that makes it difficult to determine the specific contribution of GABAA receptors in shaping the synaptic output of individual retinal cell types (Hoon et al, 2015; Wassle et al, 1998; Figure 1B) Due to these limitations, most studies investigating the role of GABAergic presynaptic inhibition in shaping the light sensitivity of ON BC synapses have largely been restricted to evaluating GABAC receptor-mediated inhibition that is localized to BCs (Oesch and Diamond, 2019; Pan et al, 2016; Sagdullaev et al, 2006). This motivated us to use genetic manipulations that selectively eliminate GABAA receptors from ON BC axon terminals to study the role of GABAA receptor-mediated presynaptic inhibition in regulating light evoked function in the tractable retinal circuit of the ONa GC with known cell types and a well-established pathway for dim light and day light signals
Sign-in/Register to view highlights & summary 
Published Version
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call