How the Brain Actively Shapes Our Feelings in Real Time

The cerebral cortex processes sensory information through a sophisticated network of neuronal connections. In what manner are these signals modified to enhance perception? A team from the University of Geneva (UNIGE) has discovered a method via which specific thalamic inputs influence neurones and alter their activity. This study, published in Nature Communications, uncovers an unrecognised mode of communication between the thalamus and the somatosensory cortex. This may elucidate why identical sensory stimuli do not consistently provoke the same sensation and may pave the way for new insights into certain mental diseases.

A singular sensory stimulus may be distinctly recognised at certain moments while appearing indistinct at others. This phenomena can be elucidated by the manner in which the brain synthesises stimuli. For instance, tactile interaction with an object beyond our visual area may suffice for identification…or may not. These perceptual changes are inadequately comprehended, although may be influenced by factors such as attention or the intrusive presence of additional stimuli. Neuroscientists assert that upon tactile contact, sensory signals from skin receptors are processed by a specialist area known as the somatosensory cortex.

En route to their destination, impulses traverse a complex neuronal network, including a critical brain structure known as the thalamus, which functions as a relay station. Nonetheless, the process is reciprocal. A substantial segment of the thalamus receives feedback from the cortex, establishing a loop of reciprocal communication. The precise nature and operation of this feedback loop remain ambiguous. Can it actively influence our perception of sensory information?

A novel modulatory route

To investigate this inquiry, neuroscientists at UNIGE examined an area at the apex of pyramidal neurones within the somatosensory cortex, abundant in dendrites—extensions that receive electrical impulses from other neurones. Pyramidal neurones possess peculiar morphologies. They exhibit asymmetry in both form and function. Anthony Holtmaat, a full professor at the Department of Basic Neurosciences (NEUFO) and director of the Synapsy Centre for Neuroscience Research for Mental Health at UNIGE’s Faculty of Medicine, elucidates, “The processes occurring at the apex of the neurone differ from those at its base.”

His team concentrated on a pathway wherein the apices of pyramidal neurones in mice receive projections from a distinct region of the thalamus. Stimulating the animal’s whiskers—analogous to human touch—uncovered a precise interaction between these projections and the dendrites of pyramidal neurones. “What is noteworthy, in contrast to the typical thalamic projections that activate pyramidal neurones, is that the thalamic region supplying feedback modulates their activity, specifically by enhancing their sensitivity to stimuli,” states Ronan Chéreau, senior researcher at NEUFO and co-author of the study.

An unforeseen receptor

The research team employed advanced techniques—imaging, optogenetics, pharmacology, and mostly electrophysiology—to capture the electrical activity of minute structures like dendrites. These methodologies elucidated the mechanisms of this regulation at the synaptic level. Typically, the neurotransmitter glutamate functions as an activation signal. It facilitates the transmission of sensory information between neurones by eliciting an electrical response in the subsequent neurone.

The recently identified process involves glutamate produced from thalamic projections binding to an alternate receptor situated in a distinct area of the cortical pyramidal neurone. This contact modifies the neuron’s response, thereby preparing it for subsequent sensory input instead of directly stimulating it. The neurone thereafter becomes more readily excitable, as though it is being conditioned to respond more effectively to an impending sensory stimuli.

This represents an unrecognised mechanism for modulation. Ronan Chéreau elucidates that the modulation of pyramidal neurones is typically maintained via the equilibrium between excitatory and inhibitory neurones, rather than by this particular process.

Consequences for perception and disorders

The work illustrates that a particular feedback loop between the somatosensory cortex and the thalamus can influence the excitability of cortical neurones, indicating that thalamic pathways function not merely as conduits for sensory inputs, but also as selective amplifiers of cortical activity. “Our perception of touch is influenced not only by incoming sensory information but also by dynamic interactions within the thalamocortical network,” states Anthony Holtmaat. This technique may also enhance comprehension of the perceptual flexibility evident in states of sleep or awake, during which sensory thresholds fluctuate. Its modification may also contribute to specific illnesses, including autism spectrum disorders.

Original Publication
Authors: Federico Brandalise, Ronan Chéreau, I-Wen Chen, David van Oorschot, Claudia Morin Raig, Tanika Bawa, Nandkishor Mule, Stéphane Pagès, Foivos Markopoulos and Anthony Holtmaat.
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