Homogeneous processing in the striatal direct and indirect pathways: single body part sensitive type IIb neurons may express either dopamine receptor D1 or D2

Abstract

Striatal medium spiny projection neurons (MSNs) output through two diverging circuits, the 'direct and indirect pathways' which originate from minimally overlapping populations of MSNs expressing either the dopamine receptor D1 or the dopamine receptor D2. One modern theory of direct and indirect pathway function proposes that activation of direct pathway MSNs facilitates output of desired motor programs, while activation of indirect pathway MSNs inhibits competing motor programs. A separate theory suggests that coordinated timing or synchrony of the direct and indirect pathways is critical for the execution of refined movements. These hypotheses are made testable by a common type of striatal neuron known as type IIb MSNs. Clusters of these MSNs exhibit phasic increases in firing rate related to sensorimotor activity of single body parts. If these MSNs were to reside in only the direct pathway, evidence would be provided that D1 MSNs are 'motor program' specific, which would lend credence to the 'competing motor programs' hypothesis. However, if type IIb MSNs reside in both pathways, evidence would be provided for the 'coordinated timing or synchrony' hypothesis. Our results show that type IIb neurons may express either D1 or D2. This evidence supports the theory that the coordinated timing or synchrony of the direct and indirect pathways is critical for refined movements. We also propose a model in which the direct and indirect pathways act as a differentiator circuit, providing a possible mechanism by which coordinated activity of D1 and D2 neurons may output meaningful somatosensorimotor information to downstream structures.

Unbalanced Inhibitory/Excitatory Responses in the Substantia Nigra Pars Reticulata Underlie Cannabinoid-Related Slowness of Movements

“…5; Kolomiets et al, 2003;Freeze et al, 2013;Brown et al, 2014). In our preparation, somesthetic stimulations potentially activating both pathways (Coffey et al, 2017) also produced inhibitory/excitatory patterns in the SNr (Fig. 1), similar to those previously described, but evoked by electrical stimulation of motor and premotor cortices (Antonazzo et al, 2019) or electrical and chemical activation of the striatum (Dray et al, 1976;Chevalier et al, 1985;Deniau and Chevalier, 1985).…”

“…1G, bottom). Thus, in this preparation, somesthetic stimulations produced somatosensory representations in the population dynamics of the SNr characterized by transient inhibitions followed by transient excitations, potentially reflecting a balanced direct-indirect pathway activation (Coffey et al, 2017).…”

No Discrete Start/Stop Signals in the Dorsal Striatum of Mice Performing a Learned Action

“…A role of the dorsal striatum in providing moment-to-moment movements representation can not be overlooked, as the dorsocentral/lateral striatal regions in which we (and others) recorded neuronal activity receive massive cortical input from motor and sensory regions related to movements and stimulation of different body parts, mainly the trunk, limbs and, to a lesser extent, oro-facial regions [13,14]. Moreover, it has been shown that the spiking activity of dorsal striatal putative FSI and direct and indirect-pathway PN is strongly modulated by passive manipulations of body parts in mice and rats [23,41]. Finally, large-scale calcium imaging of both direct and indirect-pathway PN activity has revealed that distinct behavioral patterns associated with openfield exploration are fully mapped in the dorsal striatum [42].…”

To move or to sense? Incorporating somatosensory representation into striatal functions

“…This possibility has not been directly tested but several recent works suggest that this interpretation should not be discarded. Coffey et al [47 ] used optrodes to identify dSPN and iSPN and found that about half of the recorded neurons in both populations increased their firing rate sharply in response to the passive stimulation of a given body part. In addition, it was shown in mice trained to perform a head-movements task that the firing rate of putative SPN is perfectly correlated with head-movements velocity [48].…”