The brain’s cerebral cortex produces perception based on the sensory information it’s fed through a region called the thalamus.
“How the thalamus communicates with the cortex in a fundamental feature
of how the brain interprets the world,” said the senior author. Despite
the importance of thalamic input to the cortex, neuroscientists have
struggled to understand how it works so well given the relative paucity
of observed connections, or “synapses,” between the two regions.
To help close this knowledge gap, the authors applied several innovative methods. In a new study in Nature Neuroscience,
the team reports that thalamic inputs into superficial layers of the
cortex are not only rare, but also surprisingly weak, and quite diverse
in their distribution patterns. Despite this, they are reliable and
efficient representatives of information in the aggregate, and their
diversity is what underlies these advantages.
Essentially, by meticulously mapping every thalamic synapse on 15
neurons in layer 2/3 of the visual cortex in mice and then modeling how
that input affected each neuron’s processing of visual information, the
team found that wide variations in the number and arrangement of
thalamic synapses made them differentially sensitive to visual stimulus
features. While individual neurons therefore couldn’t reliably interpret
all aspects of the stimulus, a small population of them could together
reliably and efficiently assemble the overall picture.
“It seems this heterogeneity is not a bug, it’s a feature that provides
not only a cost benefit, but also confers flexibility and robustness to
perturbation” said the corresponding author of the study.
“Thousands of information inputs pour into a single brain cell. The
brain cell then interprets all that information before it communicates
its own response to the next brain cell,” another author said. “What is
new and we feel exciting is we can now reliably describe the identity
and the characteristics of those inputs, as different inputs and
characteristics convey different information to a given brain cell. Our
techniques give us the ability to describe in living animals where in
the structure of the single cell what kind of information gets
incorporated. This was not possible until now.”
The team chose layer 2/3 of the cortex because this layer is where there
is relatively high flexibility or “plasticity,” even in the adult
brain. Yet, thalamic innervation there has rarely been characterized.
Moreover, the author said, even though the model organism for the study
was mice, those layers are the ones that have thickened the most over
the course of evolution, and therefore play especially important roles
in the human cortex.
Precisely mapping all the thalamic innervation onto entire neurons in
living, perceiving mice is so daunting it’s never been done.
To get started the team used a technique established
in the lab that enables observing whole cortical neurons under a
two-photon microscope using three different color tags in the same cell
simultaneously, except in this case, they used one of the colors to
label thalamic inputs contacting the labeled cortical neurons. Whereever
the color of those thalamic inputs overlapped with the color labeling
excitatory synapses on the cortical neurons that revealed the location
of putative thalamic inputs onto the cortical neurons.
Two-photon microscopes offer deep looks into living tissues, but their
resolution is not sufficient to confirm that the overlapping labels are
indeed synaptic contacts. To confirm their first indications of thalamic
inputs, the team turned to a technique called MAP. MAP physically
enlarges tissue in the lab, effectively increasing the resolution of
standard microscopes. The authors were able to combine the new labeling
and MAP to definitely resolve, count, map, and even measure the size of
all thalamic-cortical synapses onto entire neurons.
The analysis revealed that the thalamic inputs were rather small
(typically presumed to also be weak and maybe temporary), and accounted
for between 2 and 10 percent of the excitatory synapses on individual
visual cortex neurons. The variance in thalamic synapse numbers was not
just at a cellular level, but also across different “dendrite” branches
of individual cells, accounting for anywhere between zero and nearly
half the synapses on a given branch.
These facts presented the team with a conundrum. If the thalamic inputs
were weak, sparse and widely varying, not only across neurons but even
across each neuron’s dendrites, then how good could they be for reliable
information transfer?
The computational model showed that when the cells were fed visual
information (the simulated signals of watching a grating go past the
eyes) their electrical responses varied based on how their thalamic
input varied. Some cells perked up more than others in response to
different aspects of the visual information, such ascontrast or shape,
but no single cell revealed much about the overall picture. But with
about 20 cells together, the whole visual input could be decoded from
their combined activity—a so-called “wisdom of the crowd.”
Notably, the authors compared the performance of cells with the weak,
sparse and varying input akin to what the lab measured, to the
performance of a group of cells that all acted like the best single cell
of the lot. Up to about 5,000 total synapses, the “best” cell group
delivered more informative results but after that level, the small, weak
and diverse group actually performed better. In the race to represent
the total visual input with at least 90 percent accuracy, the small weak
and diverse group reached that level with about 6,700 synapses while
the “best” cell group needed more than 7,900.
“Thus heterogeneity imparts a cost reduction in terms of the number of
synapses required for accurate readout of visual features,” the authors
wrote.
The senior author said the study raises tantalizing implications
regarding how thalamic input into the cortex works. One, the author
said, is that given the small size of thalamic synapses they are likely
to exhibit significant “plasticity.” Another is that the surprising
benefit of diversity may be a general feature, not just a special case
for visual input in layer 2/ 3. Further studies, however, are needed to
know for sure.
https://www.nature.com/articles/s41593-022-01253-9