Hyperexcitable primary somatosensory cortex in the MitoPark mouse model of Parkinson's disease

Parkinson's disease patients often experience decreased tactile acuity or neuropathic pain, which can significantly impact their quality of life and worsen motor dysfunction. The relationship between Parkinson's pathology and altered somatosensation is not yet understood. One possible factor is the gradual loss of dopamine neurons.

To investigate this, researchers recorded spontaneous and stimulus-evoked activity in the primary somatosensory cortex of MitoPark mice, a mouse model of Parkinson's disease. MitoPark mice exhibit progressive dopamine neuron degeneration that is not linked to the presence of alpha-synuclein proteins.

The study found that layer V regular-spiking neurons, which are largely pyramidal in structure, had higher spontaneous firing rates compared to control mice at later stages of symptom progression. Additionally, these regular-spiking neurons became hyperresponsive to tactile stimuli, with more neurons responding to a wide range of stimuli intensities and exhibiting stronger firing rates upon stimulation.

In contrast, fast-spiking neurons, predominantly parvalbumin-expressing inhibitory cells, became desynchronized at later stages of symptom progression. These physiological changes were observed alongside substantial dopamine neuron and axon degeneration, which was measured through tyrosine hydroxylase immunostaining in the midbrain, striatum, and primary somatosensory cortex.

By combining these findings, the researchers concluded that cell-type-specific changes in the primary somatosensory cortex are consistent with both decreased tactile acuity and increased hyperalgesia in Parkinson's disease patients. This suggests that the loss of dopamine neurons, potentially including those innervating the primary somatosensory cortex, may contribute to somatosensory impairments associated with the disease.