Singing modulates parvalbumin interneurons throughout songbird forebrain vocal control circuitry.

Across species, the performance of vocal signals can be modulated by the social environment. Zebra finches, for example, adjust their song performance when singing to females ('female-directed' or FD song) compared to when singing in isolation ('undirected' or UD song). These changes are salient, as females prefer the FD song over the UD song. Despite the importance of these performance changes, the neural mechanisms underlying this social modulation remain poorly understood. Previous work in finches has established that expression of the immediate early gene EGR1 is increased during singing and modulated by social context within the vocal control circuitry. Here, we examined whether particular neural subpopulations within those vocal control regions exhibit similar modulations of EGR1 expression. We compared EGR1 expression in neurons expressing parvalbumin (PV), a calcium buffer that modulates network plasticity and homeostasis, among males that performed FD song, males that produced UD song, or males that did not sing. We found that, overall, singing but not social context significantly affected EGR1 expression in PV neurons throughout the vocal control nuclei. We observed differences in EGR1 expression between two classes of PV interneurons in the basal ganglia nucleus Area X. Additionally, we found that singing altered the amount of PV expression in neurons in HVC and Area X and that distinct PV interneuron types in Area X exhibited different patterns of modulation by singing. These data indicate that throughout the vocal control circuitry the singing-related regulation of EGR1 expression in PV neurons may be less influenced by social context than in other neuron types and raise the possibility of cell-type specific differences in plasticity and calcium buffering.

Bilateral lesions of the nigrostriatal pathways are associated with chronic mechanical pain hypersensitivity in rats.

Some patients with Parkinson's disease (PD) suffer from pain before motor symptoms. To model this, we proposed to assess the mechanical hypersensitivity in an animal model of PD with a bilateral lesion of the nigrostriatal pathway. PD model was validated by a decrease of locomotor activity and a 76% dopamine cell loss in the substantia nigra pars compacta. PD animals displayed a decrease of mechanical thresholds, correlated with the degree of the dopamine lesion. This animal model displays nociceptive disorders as found in PD patients and could be useful to assess the effects of new antiparkinsonian drugs.

Motivational properties of D2 and D3 dopamine receptors agonists and cocaine, but not with D1 dopamine receptors agonist and L-dopa, in bilateral 6-OHDA-lesioned rat.

Dopamine dysregulation syndrome in Parkinson's disease (PD) has been attributed to dopamine replacement therapy (DRT). We hypothesize that DRT can induce a potential rewarding effect in an animal model of PD. Using the conditioned place preference (CPP) paradigm, we investigated the motivational effects of L-dopa, dopamine receptor agonists (DRAs), and cocaine in rat with a bilateral 6-OHDA lesion of the nigrostriatal dopaminergic pathway. In 6-OHDA animals, D1 receptors agonist (SKF81297) revealed significantly a conditioned place aversion (CPA) at 3 mg/kg and 9 mg/kg doses. D2 receptors agonist (bromocriptine) induced both CPP and CPA at 1 mg/kg and 10 mg/kg doses respectively. D3 receptors agonist (PD128907) induced a CPP only at 1 mg/kg, comparable to that of cocaine. Sham animals revealed biphasic CPP curves, with significant dose effect, for the intermediate dose of the 3 DRAs. However, L-dopa induced no significant effect while cocaine induced CPP in both lesioned and sham animals. In conclusion, this study confirms the predominant roles of D2R class, and most specifically D3R subtypes, in rewarding properties of DRT.