Role of Dopamine in Normal Rodent Motor Cortex: Physiological Effects and Structural Correlates

摘要

Dopamine (DA) has been implicated in the cortical pathophysiology of several neurological disorders. Until recently, motor areas of the neocortex were thought to receive only sparse DA innervation. It is now known that the motor cortex of rodents and primates are densely innervated by DA, but its detailed circuitry and role in motor cortex function remain unclear. Immunohistochemistry and in situ hybridization were used to determine the laminar distribution and morphology of neurons that contain the protein and mRNA for the D1a, D2, and D5 receptors. Numerous pyramidal-shaped neuronal somata in layers II-VI of rodent motor cortex were immunoreactive for the D1a, D2, and D5 receptors, and sparse nonpyramidal-shaped neurons in layers V-VI were immunoreactive for the D1a receptor. Quantitative analysis revealed that all three receptor subtypes were expressed by neurons with distinct laminar distributions. Double label immunohistochemistry was used to determine if DARPP- 32, a phosphoprotein that acts as part of the D1 receptor signal transduction cascade, co-localized D1a, D2, or D5 receptors in motor cortex neurons. DARPP- 32 was co-localized with D1a and D2 receptors in pyramidal-shaped neurons in layers V-VI, and with D5 receptors in neurons of deep layer VI. Tract tracing and immunohistochemical techniques were used to determine if pyramidal tract neurons (PTNs), output neurons from the motor cortex to the spinal cord, possess D1a, D2, or D5 receptors. All three receptor subtypes were found in identified PTNs. Locally applied DA induces both inhibitory and excitatory responses in the neocortex. Electrophysiological techniques were employed to determine the effects of iontophoretically applied DA on the spontaneous activity (SA) of PTNs, the receptors that mediate these effects, and DA's effects on glutamate-induced excitation of PTNs. The findings indicate that DA may have profound effects on motor cortex activity, through its influence on PTNs.