Fig. 3

Schematic of common DBS targets and their connections in mice. The subthalamic nucleus (STN) and the globus pallidus internus (GPi) are the primary DBS targets in PD [5,6,7,8]. The STN receives excitatory input from the cortex, referred to as the hyperdirect pathway [35], and from thalamic areas like the parafascicular nucleus [120]. Its main inhibitory input comes from the globus pallidus externus (GPe), contributing to the indirect pathway. STN neurons are primarily glutamatergic and project efferent fibers to the GPi and substantia nigra pars reticulata (SNr) to convey motor information. Notably, STN neurons also project to the caudate putamen (CPu), as demonstrated by viral tracing experiments in mice [225]. The GPi primarily receives glutamatergic afferents from STN and GABAergic input from the GPe and CPu. GPi sends GABAergic efferents to the thalamus and lateral habenula (LHb) [130]. The pedunculopontine nucleus (PPN) is a component of the mesencephalic locomotor region and is targeted to address gait and postural instability issues [12, 13]. In addition to its descending projections to the medulla and spinal cord, PPN neurons project to multiple ascending targets, including the thalamus and several basal ganglia components. These projections comprise a mixture of cholinergic and noncholinergic afferents [226]. A significant portion of inputs to the PPN originates in brainstem and midbrain structures, including the substantia nigra pars compacta (SNc) and SNr. PPN neurons also receive direct input from the zona incerta (ZI) in the hypothalamus [163]