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Thalamocortical feedback selectively controls pyramidal neuron excitability.

Federico Brandalise^1,2, Ronan Chéreau¹, I-Wen Chen¹

¹Department of Basic Neurosciences and the Geneva University Neurocenter, Centre Médical Universitaire (CMU), University of Geneva, Geneva, Switzerland.

Nature Communications

|July 2, 2025

Summary

This summary is machine-generated.

Higher-order thalamic projections selectively enhance excitability in specific mouse cortical neurons. This occurs via NMDA receptor (NMDAR) and group 1 metabotropic glutamate receptor (mGluRI) signaling, modulating neuronal activity.

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Area of Science:

Neuroscience
Cellular Neuroscience
Systems Neuroscience

Background:

Layer (L) 2/3 pyramidal neurons in the mouse somatosensory cortex receive long-range synaptic inputs.
The role of higher-order thalamic projections, specifically from the posteromedial nucleus, in sensory processing remains unclear.

Purpose of the Study:

To investigate how inputs from the posteromedial nucleus influence sensory-evoked cortical activity.
To elucidate the cellular mechanisms underlying the regulation of neuronal excitability by higher-order thalamocortical projections.

Main Methods:

Ex vivo electrophysiological recordings of mouse somatosensory cortex.
In vivo calcium imaging of neuronal activity.
Pharmacological manipulation of signaling pathways (mGluRI).

Main Results:

Higher-order thalamic projections provide dense synaptic input to broad tufted L2 neurons.
These inputs cooperate to generate NMDA spikes and increase neuronal excitability by blocking two-pore domain potassium leak channels via mGluRI signaling.
Slender tufted neurons and other projections do not activate these mechanisms.
In vivo imaging confirmed mGluRI-dependent modulation of feedback-mediated spiking in L2.

Conclusions:

Higher-order thalamocortical projections regulate neuronal excitability in a cell type- and input-selective manner.
Fast NMDA receptor (NMDAR) and mGluRI-dependent mechanisms are crucial for this regulation.
This provides a novel insight into the role of higher-order thalamus in sensory processing.