Possible Contribution of the Basal Ganglia Brainstem System to the Pathogenesis of Parkinson’s Disease

Insight into the organization of the motor and non-motor symptoms in Parkinson’s disease (PD) is critical for understanding the role of basal ganglia in the control of behavioral expression. Motor symptoms are generally characterized by hypokinesia-bradykinesia, resting tremor, muscular rigidity and posture-gait disabilities (Morris et al., 1994; Murrey et al., 1978). Sleep disturbances are major non-motor symptoms, which include insomnia, narcolepsy-like sleep attack and rapid eye movement (REM) sleep behavioral disorder (RBD) (Ferini-Strambi & Zucconi, 2000; Iranzo et al., 2006; Postuma et al., 2010; Schenck, 1996), in addition to disturbances of emotional expression and impairments of cognitive and executive functions (Aarsland et al., 2010). It has been well established that the cortico-basal ganglia loops (C-BG loop) contribute to the volitional and intentional control of movements (Delong & Wichmann, 2007). Basal ganglia outflow directly toward to the midbrain of the brainstem (basal ganglia-brainstem system; BG-BS system) has been recently recognized with respect to the regulation of muscle tone and posture-gait synergy (Takakusaki et al., 2003a, 2004c). It has been suggested that the BG-BS may also contribute to the modulation of vigilance states (Takakusaki et al., 2004c, 2005). Fundamental structures involved in the control of posture and locomotion and those in the muscle tone regulation during awake-sleep states exist in the brainstem and spinal cord (Chase & Morales 1990; Takakusaki et al., 1993, 1994, 2004a, 2006). The importance of the midbrain area including the pedunculopontine tegmental nucleus (PPN) has been particularly recognized in relation to these functions (Palphill & Lozano 2000; Datta, 2002; Rye 1997). The PPN and a vicinity of this nucleus (PPN area) receive excitatory projections from the cortical motor areas (Matsumura et al., 2000) and the limbic system via the hypothalamus. The PPN is also a major target of GABAergic projections from the basal ganglia output nuclei (Moriizumi et al., 1988; Rye et al., 1987; Span & Grofova, 1991; Lavoie & Parent 1994). The purpose of this review is to facilitate understanding the pathophysiological mechanism of motor and non-motor functions in PD. For this, we first refer general framework in the central nervous system for movement control in relation to volitional, emotional and