Subregions of the caudate nucleus and their in- and output channels in oro-facial dyskinesia: a behavioural and retrograde tracing study in the cat

Abstract

Previous studies have shown that the feline caudate nucleus contains DPI-sensitive (caput nuclei caudati, anterodorsal part; r-CRM) and DPI-insensitive (caput nuclei caudati, rostromedial part; CRM) regions. Stimulation of dopamine receptors within the r-CRM by dopamine or DPI are known to elicit oro-facial dyskinesia (OFD), i.e. a syndrome of tic-like contractions of the facial muscles in combination with tonque protrusions. OFD is also elicited from the sub-commissural part of the globus pallidus (scGP), a first order output station of the r-CRM, but not from the CRM. On the basis of these data it has been hypothetized that (1) OFD is a specific feature of the r-CRM, but not the CRM; (2) effects elicited from the r-CRM are funneled via the scGP, and that (3) r-CRM and CRM are differentially innervated. Cats were bilaterally equipped with cannulas directed at the CRM or r-CRM and scGP. Following recovery from the operation the cats received bilateral injections of DPI into CRM (5 μg/5μl) or r-CRM (5 and 10 μg/5 μl), the latter in combination with muscimol (50 and 100 ng/1 μl) into the scGP or its solvent. Subsequentl, behaviour was analayzed. OFD, quantified in number of tongue protrusions, was only elicited from the r-CRM, but not from the CRM confirming previously reported data in this respect. Furthermore the effect varied according to the dose used. The OFD elicited from the r-CRM was found to be blocked at the level of the scGP by local injections of muscimol, a GABA agonist. Furthermore it was found that the OFD elicited from the scGP by injections of picrotoxin or carbachol, i.e. a syndrome which was previously studied, was highly comparable with that elicited from the r-CRM. These data together allow the conclusion that effects elicited from the r-CRM such as OFD are anyhow funneled via the scGP. Finally, it was found in retrograde tracing experiments that r-CRM and CRM are differentially innervated by mesencephalic A8 and A9 cells. In sum, the present study provides direct evidence that OFD is a characteristic feature of a particular subregion within the caudate nucleus which has its own input and output channels.