Abstract
Purpose :
Inhibition regulates the output of neural circuits by modulating neuronal function at both the pre- and postsynapse. In the retina, presynaptic inhibition regulates neurotransmitter release from the axon terminals of second-order neurons, bipolar cells (BCs), and modifies feedforward signaling from BCs to retinal output neurons, ganglion cells (GCs). We know a great deal about the localization and molecular composition of GABA and Glycine receptors that mediate presynaptic inhibition at BC terminals. However, a lack of BC subtype specific perturbations has limited our understanding of how presynaptic inhibition shapes functional output across distinct retinal pathways, specifically across both ON and OFF circuits that respond to light increments and decrements respectively. Here, we use a transgenic approach which eliminates axonal or both axonal and dendritic GABAA receptors from select BC types in mouse retina to investigate the role of presynaptic inhibition in shaping GC function. In addition, we explore how presynaptic inhibition in the ON pathway shapes OFF GC function.
Methods :
We used single cell patch-clamp electrophysiology to record light responses from two major ON and OFF GC types (the ‘alpha’ GCs) in murine transgenic and littermate control retinal whole mount preparations.
Results :
We find that selective loss of GABAA receptors from ON BC axons versus from both axons and dendrites differentially affects the amplitude and kinetics of light responses in the ON alpha GC pathway. Furthermore, we find that absence of axonal GABAA presynaptic inhibition affects the basic properties of synapse and circuit function in the ON alpha GC pathway. Additionally, we find that absence of presynaptic inhibition in ON BC axons impacts rod-mediated signaling in an OFF alpha GC pathway.
Conclusions :
In this study, we highlight the potential roles of location-specific inhibition in modulating behaviorally relevant retinal circuit processes. Further, we provide details about the functional implications of presynaptic inhibition in visual signals across major retinal pathways.
This abstract was presented at the 2023 ARVO Annual Meeting, held in New Orleans, LA, April 23-27, 2023.