How the brain merges sensory input with context

What we see, hear, smell, or feel upon touch is not simply a reaction of our brains to incoming sensory signals. Instead, our perception of the world results from mechanisms that combine these external signals with internally generated information streams reflecting our experiences, expectations, and emotions. Our scientists have now identified the mechanism that accounts for the first stage of this process in the cerebral cortex – the brain region crucial for cognition. Surprisingly, it is the sensory input itself that triggers its combination with other signals arriving during or even before the stimulus. These findings, published in Nature Communications, open new perspectives on how the brain transforms sensory signals into perception.

Scientists from our In Silico Brain Sciences Lab and the Vrije Universiteit Amsterdam investigated how the rat brain processes sensory signals from whiskers on the snout. Similar to human fingertips, rats use their whiskers as highly developed touch sensors to explore their environment. Sensory signals from the whiskers reach the cortex via the thalamus, the central hub for externally generated information. When investigating how neurons in the thalamus form synaptic connections with cortical neurons, the team made a key discovery: thalamocortical (TC) synapses clustered densely around a calcium channel–rich domain of the brain’s major cortical output neurons, called pyramidal tract neurons (PTs).

“It was totally unexpected to see that neurons from the thalamus are capable of targeting a specific dendritic domain in a specific cell type of the cortex. This extreme level of specificity suggested that sensory signals from the whiskers could contribute to dendritic calcium signals, enabling PTs to combine inputs that arrive at different cortical layers,” explains Dr. Jason M. Guest, one of the study’s lead authors.

To test this, the team went far beyond anatomy. They developed realistic computer models of the cerebral cortex to simulate the flow of sensory signals in the living animal.

“The simulations not only predicted the activity we recorded in vivo,” adds Dr. Arco Bast, co–lead author of the study. “They essentially revealed the underlying mechanism, which we termed TC coupling. The simulations even suggested how we could test this in living animals, which we later confirmed using optogenetic manipulations of TC synapses.”

The scientists also investigated how TC coupling changes the responses PTs broadcast to downstream brain regions. In the absence of additional inputs, sensory signals evoked single action potentials. In contrast, the very same signals produced short bursts of three action potentials when combined with ongoing inputs through TC coupling.

“Our study shows that even the very first sensory responses leaving the cortex are shaped by inputs that precede the stimulus,” says Professor Marcel Oberlaender, head of the In Silico Brain Sciences Lab. “The finding that bursts of three action potentials provide a neurophysiological signature for this coupling process opens new possibilities to investigate how the brain transforms sensation into perception – and why context shapes what we actually experience.”

Reference:

Bast, Guest, Fruengel, Narayanan, de Kock & Oberlaender (2025). Thalamus enables active dendritic coupling of inputs arriving at different cortical layers. Nature Communications (read the full article).