Visual perception relies on rare and diverse thalamic inputs of cortical neurons

Our survival depends on our ability to observe the world around us accurately and reliably. Visual impairment occurs in a variety of psychiatric and neurodevelopmental disorders, including autism, schizophrenia, and stroke. To perceive the world, we rely on the cerebral cortex to assimilate sensory information relayed through the thalamus.

“How the thalamus communicates with the cortex in a fundamental feature of how the brain interprets the world,” says Ellie Nedevi, a professor at the Massachusetts Institute of Technology’s Picower Learning and Memory Institute.

However, there is little connection between the thalamus and the cerebral cortex, confusing neuroscientists about how we can perceive the world.

Dr Simon Schultz, Professor of Neuroengineering at Imperial College London, said: It arises internally from the cortex itself. But there was always the potential for those inputs to be so powerful that they could still make a big impact. “

To solve this problem, Nedibi and her collaborators, both inside and outside the Massachusetts Institute of Technology, used several innovative methods and reported their findings in the journal Nature Neuroscience last week “Mapping thalamic innervation to individual L2/3 pyramidal neurons to model visual input ‘reading’They found that thalamic inputs to the superficial layers of the cortex were not only rare, but their distribution was weak and variable. Still, they help form a reliable and efficient representation of the aggregated information.

The authors meticulously mapped all thalamic synapses of 15 neurons in layer 2/3 of the mouse visual cortex and modeled how inputs affect each neuron’s ability to process visual information. bottom. This is the first study to precisely map all thalamic innervation across cortical neurons in living mice.

The researchers found that wide variations in the number and arrangement of thalamic synapses produced differences in sensitivity to visual stimulus features. Thus, while individual neurons could not reliably interpret all aspects of a stimulus, small groups of neurons could work together to effectively assemble the big picture.

“This non-uniformity doesn’t seem to be a bug. It’s a feature that offers not only a cost advantage, but also flexibility and robustness to perturbations,” said Nedivi.

Aygul Balcioglu, Ph.D., a scientist in Nedivi’s lab and lead author of the study, said the study creates a way for neuroscientists to track every individual input that a cell receives as it arrives. said.

“Thousands of information inputs are poured into a single brain cell, which interprets all that information before transmitting its response to the next brain cell,” Balcioglu said. I’m here. “What is new and exciting is that we can now reliably explain the identity and properties of these inputs, as different inputs and properties convey different information to specific brain cells. It gives us the ability to explain where and what information is embedded in the structure of a single cell, which has never been possible before.”

mapping

Nedivi’s team focused on layers 2/3 of the cortex. This is because even the adult brain is relatively flexible or plastic. The team used multicolor two-photon microscopy, established in Nedevi’s lab, to observe whole cortical neurons using his three color tags simultaneously in the same cell, contacting labeled cortical neurons. We labeled the thalamic inputs that Overlapping labels of thalamic inputs of cortical neurons and excitatory synapses revealed a putative connection.

To confirm the existence of thalamic inputs, the team used a technique called MAP (Amplified Analysis of the Proteome). The technique was invented in the lab of Dr. Kwanghun Chung, an associate professor of chemical engineering at MIT. MAP physically enlarges tissue and enhances the resolution of standard microscopy. Dr. Rebecca Gillani, a postdoctoral researcher in the Nedivi lab, with the help of her Dr. Taeyun Ku, a postdoctoral researcher in Chung’s lab, combined a new labeling technique with her MAP to resolve all thalamocortical synapses. , counted, mapped, and measured. Whole cortical neurons.

Analysis showed that thalamic inputs were fairly small, accounting for 2–10% of the excitatory synapses of individual neurons in the visual cortex. The number of thalamic synapses varies not only at the cellular level, but also among the various dendritic branches of individual neurons.

crowdsourcing

The puzzle of this discovery lies in how these weak, sparse and highly variable thalamic inputs form the basis for the reliable transmission of visual information.

To address this issue, Nedibi worked with Dr. Idan Segev, a professor of computational neuroscience at the Hebrew University of Jerusalem. Segev and his student Michael Doron built a biophysical model of cortical neurons based on findings from Nedevi’s lab and his Allen Brain Atlas.

This indicated that when cortical neurons were presented with visual information, their electrical responses changed based on changes in thalamic input. Some cells showed greater responses to contrast and shape, but no single cell revealed much about the big picture. However, we were able to decode the entire visual input from the combined activity of clusters of about 20 cells.

“Heterogeneity offers cost savings in terms of the number of synapses required for accurate reading of visual features,” the authors say.

“This is a very interesting result,” Schultz said. We show that cortical synapses are small, sparse, and even not particularly reliable!

implication

Given the small size of thalamic synapses, they are likely to exhibit considerable plasticity, Nedivi said. She also said that the advantage of diverse neuronal inputs could be a common feature.

“This research has been constructed in recent years as our ‘perceptual world’ is highly internally generated within the cerebral cortex and only sparsely updated as needed by information coming in from the cerebral cortex. I think it actually matches the diagram. outside. It’s a great paper on an important issue,” he said Schultz.

Financial support for this study was provided by the National Eye Institute of the National Institutes of Health, the Office of Naval Research, and the JPB Foundation.