image:

A cortical neuron highlighted with green fluorescent protein, captured within the brain of a living mouse using two-photon imaging.

Credit: © Ronan Chéreau

The cerebral cortex interprets sensory input through an intricate web of neuronal connections. But how are these incoming signals adjusted to sharpen perception? Researchers at the University of Geneva (UNIGE) have uncovered a new mechanism in which specific projections from the thalamus influence the activity of neurons in the cortex. Published in Nature Communications, this study uncovers a unique mode of interaction between the thalamus and the brain's somatosensory cortex. Their findings may help explain why identical sensory inputs are sometimes perceived differently and could offer insights into certain neurological conditions.

Our perception of the same touch can vary—sometimes sharp and clear, sometimes faint and indistinct. These differences in sensation may be the result of how sensory information is processed by the brain. For instance, touching an unseen object might be all it takes to identify it—or not. These perceptual inconsistencies remain mysterious, though attention and competing stimuli might play a role. What researchers do understand is that when we experience touch, the relevant signals travel to a brain region known as the somatosensory cortex.

Before reaching this destination, sensory signals journey through a network of neurons, including the thalamus—an essential structure acting as a communication hub. Interestingly, this communication doesn't flow in just one direction; the thalamus also receives input back from the cortex, creating a feedback system. Despite its importance, the precise function of this feedback mechanism is not fully understood. Could it perhaps influence how we interpret sensory information?

A newly discovered regulatory route To investigate this, UNIGE researchers examined the upper dendritic region of pyramidal neurons within the somatosensory cortex. This area is rich in input-receiving branches. “Pyramidal neurons are peculiar—they have an asymmetric design and function. The activity at the top part of the cell differs from what occurs at the base,” explains Anthony Holtmaat, professor in the Department of Basic Neurosciences (NEUFO) and director at the Synapsy Centre for Neuroscience Research in Mental Health at UNIGE’s Faculty of Medicine.

The team focused on a neural circuit where the upper segments of pyramidal neurons receive input from a particular section of the thalamus. By stimulating the mice’s whiskers—similar to the sense of touch in humans—they uncovered a precise exchange between these thalamic projections and the dendrites. “Interestingly, unlike most thalamic inputs that activate cortical neurons, this loop adjusts their sensitivity, especially by increasing their responsiveness to touch,” says Ronan Chéreau, senior researcher at NEUFO and co-author of the study.

An unanticipated receptor Using a combination of sophisticated methods—imaging, optogenetics, pharmacology, and notably electrophysiology—the scientists were able to monitor electrical responses within tiny structures such as dendrites. These tools revealed how the modulation happens at the synapse level. Typically, the chemical messenger glutamate triggers nerve activation by binding to receptors and generating electrical signals in receiving neurons.

However, in this case, the glutamate released from the thalamic input attaches to a different type of receptor found in a specific dendritic region. Instead of provoking immediate activation, this interaction changes the neuron’s internal state, making it more ready to respond to upcoming stimuli. In essence, the neuron becomes more receptive, as if being tuned in advance for sensory input.

“This is a completely new form of regulation. Normally, pyramidal neuron activity is controlled by balancing excitatory and inhibitory influences—not through this sort of direct feedback,” Chéreau notes.

Impact on perception and disease Through showing that a specific feedback circuit between the cortex and thalamus can regulate neuron sensitivity, the research highlights that thalamic input does not merely convey information but acts as a filter that can adjust the brain’s response. “Essentially, how we feel a touch is determined not only by the signal reaching us but also by ongoing interactions within the thalamus-cortex system,” says Holtmaat. This mechanism might also help explain how perception varies depending on alertness, like between sleep and being awake. Changes in this system could be connected to conditions like autism spectrum disorder.

Journal

Nature Communications

DOI

10.1038/s41467-025-60835-w

Method of Research

News article

Subject of Research

Not applicable

Article Title

"Thalamocortical feedback selectively controls pyramidal neuron excitability"

Article Publication Date

1-Jul-2025