Neuron-Specific Thalamic Connectivity Patterns Encode Spontaneous Movement in Sensory Cortex
Background: Neuronal activity in the primary somatosensory cortex (wS1) is influenced by both sensory stimuli and spontaneous movements, yet the organization of circuits that support this functional diversity remains unclear. Prior studies have shown that neuromodulators and thalamic activity correlate with behavioral state, but how these inputs contribute to movement-related cortical activity at the level of single neurons is poorly understood.
Hypothesis: This study hypothesized that functionally distinct neurons in wS1 receive inputs from anatomically distinct presynaptic networks, and that this organization underlies the stable encoding of spontaneous movement-related activity.
Methods: The authors used two-photon calcium imaging to record layer 2/3 pyramidal neuron activity in awake mice during spontaneous whisker and locomotor movements. Functionally identified neurons were electroporated with constructs encoding TVA, glycoprotein and a fluorescent marker, followed by injection of a glycoprotein-deleted rabies virus expressing red fluorescence. Whole-brain reconstructions identified monosynaptic presynaptic neurons, which were mapped and quantified using Neurolucida for three-dimensional reconstruction and NeuroInfo for anatomical registration with the CCF v3.
Results: In wS1, movement-correlated neurons increased activity during spontaneous movements, while uncorrelated neurons did not. Glutamate receptor blockade disrupted this activity, but neuromodulatory receptor blockade did not, showing glutamatergic dependence. Tracing revealed that movement-correlated neurons received fewer motor cortical and more thalamic inputs. Optogenetic suppression confirmed that only thalamic input reductions decreased movement-related activity.
Conclusions: These findings indicate that stable representations of spontaneous movement in wS1 arise from neuron-specific anatomical biases in presynaptic connectivity, primarily mediated by thalamic glutamatergic inputs rather than direct neuromodulatory control.
Inácio AR, Lam KC, Zhao Y, Pereira F, Gerfen CR, Lee S. Brain-wide presynaptic networks of functionally distinct cortical neurons. Nature 2025;641(8061):162-172. doi: 10.1038/s41586-025-08631-w.
