In songbirds, an anterior forebrain pathway has been implicated in vocal learning. Within Area X, the striatal-pallidal component of this forebrain pathway, early social tutoring dramatically increases the autophosphorylation of CaMKII (calcium-calmodulin-dependent protein kinase II). Activation of CaMKII often is associated with forms of synaptic plasticity (e.g. LTP) underlying learning and memory, and electrophysiological studies have demonstrated NMDA and dopamine (DA) receptor-dependent LTP among Area X medium spiny neurons [Ding, L., Perkel, D.J., 2002. Dopamine modulates excitability of spiny neurons in the avian Basal Ganglia. J. Neurosci. 22, 5210-5218]. Together, these data suggest that Area X neurons may help to encode a representation of song used for vocal mimicry. To identify which Area X neurons could participate in the CaMKII response to song tutoring, we used immunocytochemistry to assess the colocalization of CaMKII with several other biochemical markers that identify specific neuron classes within Area X. Virtually all (approximately 98%) Area X cells expressing CaMKII also expressed DARPP-32 (dopamine- and adenosine 3'5'-monophosphate-regulated phosphoprotein), a dopamine signaling protein enriched in medium spiny striatal neurons. The implication that medium spiny neurons are primary mediators of the pCaMKII response to tutoring is interesting in view of the established dopaminergic modulation of LTP in this cell type. Additionally, BrdU and DARPP-32 immunocytochemistry were combined to test whether medium spiny neurons are among the neurons generated and incorporated into Area X during song learning. Based upon their expression of DARPP-32, the majority of Area X neurons labeled by BrdU injections given on posthatch days 20-25 are medium spiny neurons.