Local Application of Dopamine Inhibits Pyramidal Tract Neuron Activity in the Rodent Motor Cortex

Abstract

Cortical neurons respond in a variety of ways to locally applied dopamine, perhaps because of the activation of different receptors within or among subpopulations of cells. This study was conducted to assess the effects of dopamine and the receptor subtypes that mediate the responses of a specific population of neurons, the pyramidal tract neurons (PTNs) in the rodent motor cortex. The specific subfamilies of dopamine receptors expressed by PTNs also were determined. PTNs were identified by antidromic stimulation in intact animals. Extracellular recordings of their spontaneous activity and glutamate-induced excitation were performed with multi-barrel pipettes to allow simultaneous recording and iontophoresis of several drugs. Prolonged (30 s) application of dopamine caused a progressive, nonlinear decrease in spontaneous firing rates for nearly all PTNs, with significant reductions from baseline spontaneous activity (71% of baseline levels) occurring between 20 and 30 s of iontophoresis. The D1 selective (SCH23390) and the D2 selective (eticlopride) antagonists were both effective in blocking dopamine-induced inhibition in nearly all PTNs. Mean firing levels were maintained within 3% of baseline levels during co-application of the D1 antagonist with dopamine and within 11% of baseline levels during co-application of the D2 antagonist and dopamine. SCH23390 was ineffective however, in 2 of 16 PTNs, and eticlopride was ineffective in 3 PTNs. The dopamine blockade by both antagonists in most neurons, along with the selective blockade by one, but not the other antagonist in a few neurons indicate that the overall population of PTNs exhibits a heterogeneous expression of dopamine receptors. The firing rate of PTNs was significantly enhanced by iontophoresis of glutamate (mean = 141% of baseline levels). These increases were attenuated significantly (mean= 98% of baseline) by co-application with dopamine in all PTNs, indicating dopaminergic interactions with glutamate transmission. The expression of dopamine receptors was studied with dual-labeling techniques. PTNs were identified by retrograde labeling with fast blue and the D1a, D2, or D5 receptor proteins were stained immunohistochemically. Some, but not all PTNs, showed labeling for D1a, D2, or D5 receptors. The D1a and D2 receptor immunoreactivity was observed primarily in the somata of PTNs, whereas D5 immunoreactivity extended well into the apical dendrites of PTNs. In accordance with findings of D1 and D2 receptor antagonism of dopamine's actions, the identification of three DA receptor subtypes on PTNs suggests that dopamine can directly modulate PTN activity through one or more receptor subtypes.

Comparison of the Inhibitory and Excitatory Effects of ADHD Medications Methylphenidate and Atomoxetine on Motor Cortex

“…For example, the dopaminergic projection from the ventral tegmental area (Lindvall et al, 1974) terminates on pyramidal cells and interneurons (Sesack et al, 1995) and likely regulates their excitability. Studies in cats (Huda et al, 2001) and rodents (Awenowicz and Porter, 2002) have demonstrated reduced excitability in motor neurons, which produce the MEP to TMS, after application of DA. A recent study in monkey prefrontal cortex showed that DA decreases horizontal excitatory transmission in cortical layer 5 by a D1 receptormediated mechanism (Gao et al, 2001).…”

Topography and collateralization of dopaminergic projections to primary motor cortex in rats

“…There, DA affects the activity of layer V motorneurons and the cortico-spinal tract (Awenowicz and Porter 2002;Vitrac et al 2014). Thus, besides supporting plasticity, dopaminergic projections to M1 are ideally suited to control the cortico-fugal output of the primary motor cortex.…”

Substantia nigra echomorphology and motor cortex excitability

“…There is a rich dopaminergic innervation of rat (Awenowicz and Porter, 2002) and primate (Goldman-Rakic et al, 1989) motor cortex and pyramidal tract neurones decrease spontaneous firing with application of dopamine (Awenowicz and Porter, 2002). Furthermore, there is substantial cell loss in the pre-SMA (Camicioli et al, 2007;MacDonald and Halliday, 2002) and caudal intralaminar thalamus (Henderson et al, 2000), and Lewy bodies are present in the cerebral cortex (e.g.…”