RMC responses increase after nerve ligation

Red nucleus contains distinct subdivisions. Its magnocellular part is associated with the rubrospinal system, while the parvicellular part more strongly relates to inferior-olivary circuitry. Focusing on the magnocellular component allows examination of spinal connections in hypersensitivity.

One week after left common-peroneal ligation, RMC c-Fos increases and largely overlaps CaMKIIα. Temporally controlled tagging also identifies more recruited cells. A region known for motor function changes after peripheral nerve injury.

Pinch evokes stronger RMC calcium. Slice evoked firing and miniature excitatory-current frequency/amplitude increase. Altered inputs and stronger output motivate behavioral tests.

Original figure 1RMC activity after nerve injury

Suppressing recruited cells improves responses

Activity tagging selects recruited RMC cells whose inhibition raises heat latencies and mechanical thresholds. Removing tagged cells through apoptosis also improves both measures, providing complementary evidence. Inhibition begins one week after ligation and is assessed over subsequent days, revealing a contribution during persistent post-injury hypersensitivity.

Photoinhibition of CaMKIIα-labeled cells also improves model mechanical and heat responses. Different interventions converge on a functional RMC contribution.

Original figure 2Model behavior after inhibition or cell removal

Two activation methods differ

Chemogenetic activation increases heat sensitivity in healthy males, while mechanical decreases are nonsignificant. Photostimulation lowers both thresholds and heat latencies. The population can promote sensitivity with method-dependent outcomes.

Photostimulation follows light timing while chemogenetics changes activity over longer periods. Heat sensitivity increases with both; mechanical changes are clearer with optical activation. Different activity manipulations reveal different behavioral magnitudes.

Original figure 3Population activation in healthy mice

Spinal-end inhibition reduces hypersensitivity

RMC axons reach several regions including spinal dorsal horn, or DH, an early sensory-processing site receiving descending modulation. Intrathecal CNO targeting receptor-expressing RMC spinal axons improves heat and mechanical hypersensitivity.

The spinal intervention connects broader RMC effects with a descending output. Midbrain signals contribute to spinally related sensory responses after peripheral injury.

Original figure 4RMC projections and spinal-end inhibition

Heat effects stand out in DH-projecting cells

Retrogradely selecting DH-projecting RMC cells and inhibiting them improves heat responses, with nonsignificant mechanical improvement. Forward labeling associates RMC input with CaMKIIα-labeled DH cells, adding cellular detail.

Broad RMC, spinal-terminal and projection-body manipulations have different scopes. Heat effects align across these inhibitory interventions, while the projection-cell mechanical effect is weaker. Heat and mechanical changes do not fully track each other within this descending route.

Original figure 5Projection cells and DH recipient labeling

Sensory modulation extends to a motor-related midbrain node

Projection-associated RMC recordings show reduced miniature-current frequency after inhibition. Relative amplitude falls, while absolute-amplitude comparisons are nonsignificant. These synaptic events complement activity and behavioral findings.

In adult male nerve-ligation mice, red-nucleus function extends from motor coordination to hypersensitivity modulation. RMC activity and spinal projections implicate descending signals, with intervention differences revealing functional organization.

Original figure 6Projection-associated synaptic recordings and model