Groundbreaking findings recently published in Nature Communications identified a novel subtype of amacrine cell (AC) in mouse models that sheds new light on the traditional model of how the retina processes visual information.
Give me some background first.
Established almost 50 years ago, the classical understanding of the retina’s visual input processing explains that the retina converts light into electrical signals that the optic nerve then sends to the brain.
Prior to the electrical signals being transmitted to the brain, they are processed in a dense, synaptic layer of the retina made up of a functional dichotomy (i.e., the on and off channels).
It has long been accepted that neurons make synapses in one-half of the synaptic layer when light is turned on and vice versa when light is turned off.
Tell me about ACs.
ACs are inhibitory interneurons in the retina that aid in organizing visual signals by traveling from photoreceptors that detect light to retinal ganglion cells (RGCs) that further relay these electrical signals to the brain.
There are roughly 60 different types of ACs that are specialized with different functions and difficult access points due to their location.
Now, talk about the study.
The findings from this study add nuance to the traditional understanding of the retina by identifying a subtype of AC—called the sign-inverting (SI)-AC—that establishes synapses in the on half of the synaptic layer but functions as the cells typically found in the off half.
The unique characteristics of the SI-AC allow for crossover inhibition and push-pull activation to enhance light detection by ACs and RGCs in the dark and feature discrimination in the light.
What is crossover inhibition?
Crossover inhibition is when excitation in either the on or off pathway produces an inhibition in local off or on pathways, respectively.
Previous studies have shown that crossover inhibition:
- Extends the range for light responses in some RGC types
- Compensates for the distorting effects of synaptic rectification
- Generates sustained signals in the inner retina
SI-AC can process both synaptic input and output in the same dendrites, establishing a new form of local computation of crossover inhibition.
What else is unique??
The researchers discovered that the SI-AC uses an inhibitory glutamate (neurotransmitter) receptor called mGluR8 instead of an excitatory glutamate receptor called AMPA—which is expressed by all other ACs—to receive electrical signals.
As such, SI-ACs function as a switch, converting an incoming excitatory signal into an inhibitory signal before transmitting it to downstream neurons and, lastly, to the brain.
Anything else?
The circuit design for SI-AC provided several advantages:
- Efficient use of dendritic structures, which aids in better utilization of cellular resources
- Eliminating off dendrites from SI-AC removes redundant inhibition to the off pathway
- The on inhibition and off excitation work together to control the glycine release from SI-AC to enhance the responses of postsynaptic cells in the on pathway
- The surrounding excitation and center inhibition of SI-AC produce a global crossover inhibition that can be controlled (relieved) locally with a small spot of light
Expert opinion?
According to the senior author of the study, Yongling Zhu, PhD, “This particular AC is not only a new kind of neuron, but it also exhibits a new way of conveying information from one half of the retina to the other.”
Dr. Zhu added: “This information transfer increases the sensitivity of retinal neurons to detect objects in the dark and enhances their ability to distinguish different motions in the light.”
Next steps?
The research team hopes to improve their intersectional strategy to accomplish single-cell type labeling and to follow-up with this study by demonstrating how this amacrine subtype impacts different visual pathways and downstream neurons.