‘Silent’ neurons in sensory cortex can be recruited to enhance sensory processing

The somatosensory cortex is a region of the mammalian brain that plays a crucial role in processing sensory information, including touch, temperature, and pain. Although this brain region has been the subject of much neuroscience study, its unique contributions to perceptual decision-making remain poorly understood.

Researchers at University College London (UCL) recently conducted an experiment exploring the links between mouse sensory cortex activity and perceptual decision-making. Their results, published in Neuronsuggest the existence of neurons that generally remain silent during sensory processing and yet can be recruited to enhance perception in mice.

“The study was inspired by two major advances in the field,” Oliver M. Gauld, co-author of the paper, told Medical Xpress. “The first is the development of optical tools to simultaneously record and optogenetically stimulate the same population of cortical neurons (called ‘all-optical’ interrogation at cellular resolution). The second is the development of approaches to study sensorimotor decision-making in head-fixed mice.”

In their recent study, Gauld and colleagues combined newly developed optical tools with sensorimotor tasks to study decision making in head-fixed mice. Their goal was to use these different approaches to identify neurons and patterns of cortical activity related to the generation of sensory perceptions in mice.

To conduct their study, the researchers designed a simple but powerful perceptual decision-making task. In this task, mice must determine whether a sensory stimulus delivered to their whiskers is stronger on the left or right side of their snout.

“The mice signaled their decision by licking left or right on two streams of water and were rewarded with sugar water for correct responses,” Gauld said. “We then used an optical technique called two-photon calcium imaging to record neural activity signals from the whisker-sensitive area of ​​the somatosensory cortex (also called the barrel cortex).”

“This allowed us to characterize how performing a task changed brain activity, which allowed us to identify which neurons responded to the presentation of the sensory stimulus.”

Analyzing the two-photon calcium imaging recordings they collected, Gauld and his colleagues found that the activity of a small fraction (about 15 percent) of the neurons in the animals’ cortex increased after the mice’s whiskers were stimulated. This finding is consistent with observations from previous research, which has demonstrated “sparse” cortical coding of sensory input in mice.

“The key part of our study was that we then used a sophisticated two-photon optogenetic manipulation system to stimulate different groups of neurons (essentially forcing those neurons to become active) and assessed whether this changed the animal’s perceptual choices,” Gauld explained.

“Specifically, we used a spatial light modulator (SLM) to deliver holographic light patterns into tissue. This means that the experimenter has very good control over which neurons are optogenetically stimulated, which is essential for studying how sparse sensory activity patterns causally influence behavior.”

Using a combination of two-photon calcium imaging and SLM-targeted optogenetics, the researchers were able to characterize and manipulate very sparse patterns of neuronal activity in the mouse brains while the animals performed the decision-making task.

Interestingly, the researchers found that optogenetic stimulation of “silent” neurons in the cortex strongly influenced the behavior of the mice examined in their study.

“Silent neurons are neurons that do not exhibit any task-related activity, meaning they remain inactive despite the presentation of sensory stimuli and the execution of behavioral decisions and motor actions,” Gauld said. “Experimental evidence suggests that silent neurons constitute most neurons in the superficial sensory cortex, because very few neurons fire action potentials upon sensory stimulation.”

“This is a key feature of the sparse coding hypothesis. Although the functional role of these silent neurons has remained unclear for many years, our study suggests that these neurons may play an important role in sensory processing, but only if they are first silenced.”

Overall, the results collected by this team of researchers suggest that the “silent” neurons of the sensory cortex are kept silent by a very strong inhibition of the network while the mice perform a decision-making task. However, the activation of some of these neurons, such as those carried out using optogenetic manipulation tools targeting the SLM, can significantly improve the animals’ sensory perception.

“Our results have important implications for understanding how cortical circuits implement sparse cortical coding and sensorimotor plasticity, which could be important for learning,” Gauld added.

“An interesting avenue for future research would be to study the causal role of silent neurons in other cortical areas or in other behavioral and cognitive processes. This would provide a more complete description of the role of silent neurons in the brain.”

© 2024 Science X Network