Neurons differentiate between novel and familiar stimuli

Scientists unravel circuit and synaptic mechanisms that allow animals to distinguish between unexpected and predictable stimuli

November 10, 2021

Animals need to react to changes in their environment very rapidly to secure their survival. Therefore, the reliable extraction of behaviorally useful information from sensory stimuli is an important task the brain needs to solve. An international team of scientists now shed light on why neurons in multiple sensory areas respond more strongly to novel in comparison to familiar stimuli.

Inhibitory neurons (red circles) modify their synaptic strength onto excitatory neurons (blue triangles) in a stimulus-specific way. Triangles with the same shade of blue and circles with the same shade of red represent a specific stimulus.

“Experiments in the mouse visual cortex have found that the presentation of a novel visual stimulus leads to a high response, while the presentation of a familiar visual stimulus leads to a lower response”, says head of the project, Julijana Gjorgjieva, Research Group Leader at the Max Planck Institute for Brain Research in Frankfurt and Professor for Computational Neuroscience at Technical  University of Munich, who led the work. “The high cortical response to novel stimuli suggests that such unexpected sensory signals are rapidly and reliably transmitted from primary sensory cortices to higher-order brain areas”, adds Gjorgjieva.

However, it remained unclear which circuit and synaptic mechanisms underlie the different cortical responses to novel versus familiar stimuli. To uncover these mechanisms, the scientists simulated a network model of excitatory and inhibitory spiking neurons with synapses (their points where neurons make contacts) undergoing long-term synaptic plasticity, a mechanism to strengthen synaptic connections and increase signal transmission between two neurons, based on recent patterns of activity.

“Just as in the experiments in mouse visual cortex, our model generated high cortical responses when a novel stimulus was presented, whereas repeated or familiar stimuli exhibited decreased responses”, says Christoph Miehl, graduate student in the Gjorgjieva lab and co-first author of the new study published in the journal eLife. “Our framework identifies long-term plasticity of inhibitory-to-excitatory synapses as a possible underlying mechanism of the differential responses”, explains graduate student Auguste Schulz who led the project together with Miehl.

Gjorgjieva concludes: “Our findings suggest that inhibitory plasticity plays a key role for the differentiation of sensory stimuli in sensory cortices and provides a biologically plausible mechanism to detect the novelty of stimuli, enabling us to make experimentally testable predictions.”

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