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.
All source data shown in the figures including some raw data are available in the data repository, Dryad, accessible via this link https://doi.org/10.5061/dryad.bg79cnpb4. Raw datasets are quite large in size and will be made available upon request by the corresponding author.
GABAA presynaptic inhibition regulates the gain and kinetics of retinal output neuronsDryad Digital Repository, doi: 10.5061/dryad.bg79cnpb4.
- Raunak Sinha
- Raunak Sinha
- Mrinalini Hoon
- Mrinalini Hoon
- Jenna Nagy
- Mrinalini Hoon
- Briana Ebbinghaus
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Animal experimentation: All experiments and animal care were conducted in accordance with the Institutional Animal Care and Use Committee (IACUC) of the University of Wisconsin-Madison and the National Institutes of Health. The protocol was approved by the Animal Care and Use Committee of the University of Wisconsin-Madison (Protocol ID: M006031-R01).
- Marla B Feller, University of California, Berkeley, United States
© 2021, Nagy et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
The lateral geniculate nucleus (LGN), a retinotopic relay center where visual inputs from the retina are processed and relayed to the visual cortex, has been proposed as a potential target for artificial vision. At present, it is unknown whether optogenetic LGN stimulation is sufficient to elicit behaviorally relevant percepts, and the properties of LGN neural responses relevant for artificial vision have not been thoroughly characterized. Here, we demonstrate that tree shrews pretrained on a visual detection task can detect optogenetic LGN activation using an AAV2-CamKIIα-ChR2 construct and readily generalize from visual to optogenetic detection. Simultaneous recordings of LGN spiking activity and primary visual cortex (V1) local field potentials (LFP) during optogenetic LGN stimulation show that LGN neurons reliably follow optogenetic stimulation at frequencies up to 60 Hz, and uncovered a striking phase locking between the V1 local field potential (LFP) and the evoked spiking activity in LGN. These phase relationships were maintained over a broad range of LGN stimulation frequencies, up to 80 Hz, with spike field coherence values favoring higher frequencies, indicating the ability to relay temporally precise information to V1 using light activation of the LGN. Finally, V1 LFP responses showed sensitivity values to LGN optogenetic activation that were similar to the animal's behavioral performance. Taken together, our findings confirm the LGN as a potential target for visual prosthetics in a highly visual mammal closely related to primates.
Hippocampal place cell sequences have been hypothesized to serve as diverse purposes as the induction of synaptic plasticity, formation and consolidation of long-term memories, or navigation and planning. During spatial behaviors of rodents, sequential firing of place cells at the theta timescale (known as theta sequences) encodes running trajectories, which can be considered as one-dimensional behavioral sequences of traversed locations. In a two-dimensional space, however, each single location can be visited along arbitrary one-dimensional running trajectories. Thus, a place cell will generally take part in multiple different theta sequences, raising questions about how this two-dimensional topology can be reconciled with the idea of hippocampal sequences underlying memory of (one-dimensional) episodes. Here, we propose a computational model of cornu ammonis 3 (CA3) and dentate gyrus (DG), where sensorimotor input drives the direction-dependent (extrinsic) theta sequences within CA3 reflecting the two-dimensional spatial topology, whereas the intrahippocampal CA3-DG projections concurrently produce intrinsic sequences that are independent of the specific running trajectory. Consistent with experimental data, intrinsic theta sequences are less prominent, but can nevertheless be detected during theta activity, thereby serving as running-direction independent landmark cues. We hypothesize that the intrinsic sequences largely reflect replay and preplay activity during non-theta states.