Mechanisms of aluminium neurotoxicity in oxidative stress-induced ...

INTRODUCTION
accounting each for approximately 49% (Rymar et al. 2004). The firsts exhibit high
expression of D1 receptors and send axons to the main output nuclei of BG for
movement control, GPi and SNpr, while the latters contain high expression of D2
receptors and innervate directly GPe.
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In the classical model of BG circuitry, the motor loop integrates two distinct
routes identified as “direct” and “indirect” pathways which proceed from the striatum,
especially from the putamen, and that act in opposing ways to control movement (Albin
et al. 1989, Alexander and Crutcher 1990, DeLong 1990). The “direct” pathway
facilitates voluntary movement. Striatonigral neurons project to GABAergic neurons in
GPi and SNpr, which in turn send axons to the motor nuclei of the thalamus. As the
neurotransmitter of both projections (striatum to GPi/Snpr, and Gpi/SNpr to thalamus)
is �-aminobutyric acid (GABA), which is inhibitory, the net effect of the direct pathway
activity is a disinhibition of excitatory thalamocortical projections, resulting in
activation of cortical premotor circuits and facilitation of movement. On the other hand,
the “indirect” pathway originates in striatopallidal neurons that project to GPe providing
an inhibitory effect. This region in turn sends axons to the STN (disinhibition) which
provides outflow to GPi and SNpr (excitation) enhancing the inhibitory effect of the BG
output nuclei on thalamocortical neurons, thus reducing movement (Figure 8).
Figure 8: Direct and indirect pathway in normal BG circuits, sagittal view of a mouse brain (Kreitzer
and Malenka 2008)