Striatal pathways tested
Not long ago, there was a study probing the function of the striatal circuit. Along the same lines, another recently published study reported the function of medium-spiny neurones from the direct and indirect pathway.
Medium-spiny neurones are the main output from the striatum. They project to the internal portion of the globus palidus (indirect pathway) and to the substantia nigra pars reticulata (direct pathway). In addition to the anatomical differences, medium-spiny neurones of the direct pathway express D1 type dopamine receptors while that of the indirect pathway express D2 type.
Bateup and her colleagues (2010), wanting to know the contribution of the medium-spiny neurones to the motor behaviour of the animal, designed a procedure to selectively disrupt each striatal pathway. They inserted a lox-P site in the gene of the dopamine- and cAMP-regulated phosphoprotein of 32 kD (DARPP-32). Then, they used the cre-recombinase under control of the D1- or D2-receptor promoter gene to selectively disrupt DARPP-32 disrupting the modulation of medium spiny neurons.
The corticostriatal synapse is still functional, but long-term potentiation vanishes when the DARPP-32 is absent. They also examined locomotor activity. Disrupting the direct pathway decreases motor activity, while disruption of the indirect pathway increases it. The second case is analogue to Huntington's disease. When they challenge the mice with cocaine, only the one with disrupted indirect pathway respond to cocaine by increasing the locomotor activity.
Finally, they performed a unilateral striatal leasion with 6OHDA and treated the mice with L-DOPA. The animals with disrupted direct pathway showed no dyskinesia. Thus, either “DARPP-32 might play a primary role in the generation of signalling abnormalities implicated in dyskinesia,” or diskinesia cannot manifest itself in animals with overall decreased motor activity.
At least for animals, these two papers (Bateup et al., 2010; Kravitz et al., 2010) constitute a clear proof of the striatal pathways in vivo.