Reorganization of striatal inhibitory microcircuits leads to pathological synchrony in the Basal Ganglia

Abstract

Neural synchronization plays an important role in information flow in the nervous system under healthy and pathological conditions. In this issue of Neuron, Gittis et al. show that reorganization of striatal microcircuits promotes synchronous activity and may underlie the pathological network oscillations at the root of motor symptoms described in Parkinson's disease.

Figure 1. Change in basal ganglia organization in Parkinson’s disease

In normal state (left), the direct pathway facilitates movement by decreasing the tonic inhibition of basal ganglia outputs to the thalamus, while the indirect pathway suppresses movements by increasing the inhibitory pathway. Dopamine (DA) release in the dorsal striatum from the substantia nigra pars compacta induces an excitation in the direct pathway via activation of dopaminergic D1 receptors and an inhibition in the indirect pathway via D2 receptors, thereby facilitating movement. In Parkinson’s disease (right), degeneration of dopaminergic neurons from the substantia nigra pars reticulata induces hyperactivity in indirect pathway and reduces activity in the direct pathway. This imbalance results in inhibition of voluntary movement, likely by enhancing synchronous activity in downstream targets; abnormal activity of STN and GPi emerge, resulting in a high inhibition of thalamic activity. Adapted from (Alexander and Crutcher 1990) Blue arrows: inhibitory projections; red arrows: excitatory projections; Grey arrows correspond to degeneration of dopaminergic output from the SNc.