Researchers map how individual neurons encode behavioral states

National Institutes of Health researchers have mapped how individual neurons in the primary somatosensory cortex receive brain-wide presynaptic inputs that encode behavioral states, refining our understanding of cortical activity.

Neurons in the primary somatosensory cortex process different types of sensory information and exhibit distinct activity patterns, yet the cause of these differences has remained unclear. Previous research emphasized the role of motor cortical regions in movement-related processing, but also recognized that the thalamus plays a role beyond sensory relay.

Using high-resolution single-cell mapping to trace neuronal connectivity, the team revealed that thalamic input is the primary driver for movement-correlated neurons, while motor cortical input plays a smaller role.

In the study, “Brain-wide presynaptic networks of functionally distinct cortical neurons,” published in Nature, NIH researchers used two-photon calcium imaging, optogenetics, neuropharmacology, and single-cell-based monosynaptic retrograde tracing to map presynaptic networks of individual neurons in the primary somatosensory cortex of mice. Neuronal activity was recorded over multiple days as the mice engaged in spontaneous movements.

Neurons encoding behavioral states received significantly fewer inputs from motor cortical areas and more from thalamic regions, particularly the ventral posteromedial nucleus. Optogenetic suppression of thalamic input reduced behavioral state-dependent activity, while blocking neuromodulatory inputs such as acetylcholine and noradrenaline had minimal effect.

Cortical state shifts were found to be stable across multiple days, contradicting earlier models that described them as transient. Even after pharmacological blocking of neuromodulatory inputs, the neuronal activity patterns associated with behavioral states remained intact, suggesting that glutamatergic synaptic input plays a dominant role in sustaining these representations.

Mapping presynaptic networks at a single-cell level offers a new perspective on how individual cortical neurons integrate diverse inputs to encode behavior. Findings may inform future research on neurological disorders where disrupted connectivity affects behavior and perception.

A research briefing, “Diversity in neuronal activity could be caused by differences in inputs,” by study authors Ana R. Inácio and Soohyun Lee, also published in Nature, expands on the significance of these findings.

Functionally distinct neurons, they point out, exhibit characteristic presynaptic networks, with movement neurons receiving a higher proportion of inputs from thalamic nuclei and fewer from motor cortical areas. These anatomical biases shape movement neuron identity within the somatosensory cortex.

They also explore broader implications, noting that behavioral state signals modulate neuronal activity through mechanisms beyond direct sensory feedback. Movement neuron activity persisted even when sensory input from the whisker pad was blocked, suggesting additional influences and supporting the role of thalamic input.

Neuromodulatory signals were considered, but direct release in the somatosensory cortex did not drive movement neuron activity, leaving open the possibility of indirect effects through thalamic projections.

The authors emphasize the need for further research into the nature of these behavioral state signals and their role in neuronal communication. Future studies, they suggest, could compare connectivity patterns across neurological disorders, potentially informing new therapeutic approaches.

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