The hyperdirect pathway involves direct cortical projections to the STN ( Nambu et al., 2002), which provides the fastest information flow among the three pathways ( Nambu et al., 2000). In turn, both the STN and GP also innervate the output nuclei. iMSNs project to the globus pallidus external segment (GP in rodents), which interconnects with the subthalamic nucleus (STN). dMSNs project to the output nuclei of the basal ganglia, namely the substantia nigra (SN) pars reticulata (SNr), and the globus pallidus internal segment, the latter being the homologue of the entopeduncular nucleus (EP) in rodents.

The direct and indirect pathways originate from two distinct types of striatal medium spiny neurons (MSNs), termed the direct- and indirect-pathway MSNs (dMSNs and iMSNs). Cortical projections drive three pathways in the basal ganglia: the direct, the indirect, and the hyperdirect pathways ( Bolam et al., 2000 Smith et al., 1998). Dysfunction of the motor loop leads to movement disorders such as those seen in Parkinsonian disease ( Albin et al., 1989 DeLong, 1990 Middleton and Strick, 2002 Nambu, 2008 Nambu et al., 2000 Parent and Hazrati, 1995a Redgrave et al., 2010 Wichmann and DeLong, 1996). The loop containing the motor cortex is crucial for appropriate motor control, action selection, and movement-related learning. The functions mediated by these loops depend on relevant cortical areas and brain regions receiving outputs of the basal ganglia ( Hikosaka, 2007 Middleton and Strick, 2000). Parallel loops of neural connections among the cerebral cortex, basal ganglia, and thalamus contribute to multiple aspects of behavior ( Alexander et al., 1986 Nambu, 2008 Wei and Wang, 2016). These results suggest that cortico-pallidal innervation is an additional excitatory input to the basal ganglia, and that it can affect behaviors via the cortex-basal ganglia-thalamus motor loop. The connection probability of cortico-pallidal innervation was higher for M2 than M1. FoxP2-expressing arkypallidal neurons were preferentially innervated by the motor cortex. Cortical excitation of GP neurons was comparable to that of STN neurons in slice preparations. Morphological observation revealed that the density of axonal boutons from motor cortices in the GP was 47% and 78% of that in the subthalamic nucleus (STN) from M1 and M2, respectively.

Here, we demonstrate in rats that primary and secondary motor areas (M1 and M2) make functional synaptic connections in the globus pallidus (GP), not usually thought of as an input site of the basal ganglia. The basal ganglia are critical for the control of motor behaviors and for reinforcement learning.

Globus simulation best inputs