We used the immunotoxin 192 immunoglobulin G-saporin to produce a selective cholinergic lesion in the nucleus basalis of Meynert (NBM) of rats and investigated whether the NBM lesion led to tactile hypersensitivity in the forepaw. The paw mechanical threshold test showed that the lesioned rats had a decreased threshold compared to the control. Surprisingly, there was a significant positive correlation between mechanical threshold and survival rate of NBM cholinergic neurons. Furthermore, using local field potential (LFP) recordings and voltage-sensitive dye (VSD) imaging, we found that the forepaw-evoked response in the primary somatosensory cortex (S1) was significantly enhanced in both amplitude and spatial extent in the NBM-lesioned rats. The neurophysiological measures of S1 response, such as LFP amplitude and maximal activated cortical area depicted by VSD, were also correlated with withdrawal behavior. Additional pharmacological experiments demonstrated that forepaw-evoked responses were increased in naive rats by blocking S1 cholinergic receptors with mecamylamine and scopolamine, while the response decreased in NBM-lesioned rats with the cholinergic agonist carbachol. In addition, NBM burst stimulation, which facilitates acetylcholine release in the S1, suppressed subsequent sensory responses to forepaw stimulation. Taken together, these results suggest that neuronal loss in the NBM diminishes acetylcholine actions in the S1, thereby enhancing the cortical representation of sensory stimuli, which may in turn lead to behavioral hypersensitivity.
Keywords: 192-IgG saporin; Choline acetyltransferase immunohistochemistry; Dysesthesia; Hypersensitivity; Mechanical withdrawal threshold; Nucleus basalis of Meynert; Somatosensory evoked potential; Voltage sensitive dye imaging.
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