Activation of D1-like dopamine receptors increases the NMDA-induced gain modulation through a PKA-dependent pathway in the premotor nucleus of adult zebra finches.

Interaction between dopamine (DA) and N-methyl-d-aspartate (NMDA) in the brain plays an important role in learning and memory. In the songbirds, the premotor robust nucleus of the arcopallium (RA) receives excitatory glutamatergic inputs from the high vocal center (HVC) and lateral magnocellular nucleus of the anterior nidopallium (LMAN), as well as dopaminergic inputs mostly from the periaqueductal gray (PAG) and ventral tegmental area (VTA). In zebra finch, DA potentiates the excitability of projection neurons in the RA through activation of D1-like dopamine receptors (D1 receptors). The relationship between D1 receptors and NMDA in the RA projection neurons is essentially unknown. Our previous work showed that NMDA can induce gain modulation in the RA projection neurons. Here, using the whole-cell current-clamp recording from brain slices of male zebra finches, we observed whether D1 receptors regulate the NMDA-induced gain modulation in the RA projection neurons. Our results showed that activation of D1 receptors further increased the slope (gain) of the firing frequency-injected current (f-I) relationship induced by NMDA in the RA projection neurons. Blocking D1 receptors had no effect on the NMDA-induced gain modulation in the RA projection neurons. The enhanced effects of D1 receptors agonists were blocked by protein kinase A (PKA) inhibitors. Our results suggest that activation of D1 receptors can increase the NMDA-induced gain modulation through a PKA-dependent pathway.