Direct and indirect pathways of basal ganglia: a critical reappraisal

Abstract

The basal ganglia are subcortical nuclei controlling voluntary actions and have been implicated in Parkinson's disease (PD). The prevailing model of basal ganglia function states that two circuits, the direct and indirect pathways, originate from distinct populations of striatal medium spiny neurons (MSNs) and project to different output structures. These circuits are believed to have opposite effects on movement. Specifically, the activity of direct pathway MSNs is postulated to promote movement, whereas the activation of indirect pathway MSNs is hypothesized to inhibit it. Recent findings have revealed that this model might not fully account for the concurrent activation of both pathways during movement. Accordingly, we propose a model in which intrastriatal connections are critical and the two pathways are structurally and functionally intertwined. Thus, all MSNs might either facilitate or inhibit movement depending on the form of synaptic plasticity expressed at a certain moment. In PD, alterations of dopamine-dependent synaptic plasticity could alter this coordinated activity.

Cannabinoids and Tremor Induced by Motor-related Disorders: Friend or Foe?

“…In addition, several studies have reported the high density of CB 1 Rs in striatum and the presence of AEA throughout the basal ganglia, in particular in the globus pallidus and substantia nigra [31,57,58]. The crosstalk between dopaminergic transmission and endocannabinoids signaling in the striatum nigra is also well established and there is a growing body of evidence that CB 1 R activation by endocannabinoid retrograde signaling has the potential to decrease glutamate release in a dopaminergic D 2 receptor-dependent manner [59][60][61].…”

Vitamin D<sub>3</sub> Receptor Activation Rescued Corticostriatal Neural Activity and Improved Motor Function in –D<sub>2</sub>R Tardive Dyskinesia Mice Model

“…VD 3 RA (only) treatment caused an increase in motor activity in control animals when compared with the control (untreated) animals. Neural recordings for VD 3 RA treatment showed a decline in RMS in the M1 (L4 -L6) coupled with a decreased frequency of the spike train. However, this group recorded a slight decline in CPu RMS when compared with the control (Figure 1(f)).…”

“…Several studies have shown a decline in motor function and cognition after a prolonged use of these drugs in treatment of depression and schizophrenia [7] [8]. Going further, the observed behavioral deficits were attributed, in part, to loss of dopaminergic neurotransmission in the motor and memory neural systems, predominantly due to D 2 R inhibition and abnormal calcium currents in corticostriatal outputs [3] [5].…”

“…The primary effects of these drugs involve the inhibition of dopaminergic D 2 receptor in the nigrostriatal system and cortical projections leading to persistent involuntary movements in the face, limbs, oral region, trunk and a decline in memory function [2] [3].…”

Alpha-PVP induces the rewarding effect via activating dopaminergic neuron

“…Increased DA levels in the nucleus accumbens shell stimulate the D 1 receptor in the mice treated with methamphetamine (Uno et al, 2017). The D 1 receptor activation induces the increase in cAMP levels, the activation of protein kinase A (PKA), and eventually the phosphorylation of nuclear CREB (Calabresi et al, 2014). If α-PVP has a similar mechanism with methamphetamine, phosphorylation of CREB should be detected.…”