New tricks for old dogmas: Optogenetic and designer receptor insights for Parkinson's disease

Abstract

Optogenetics and novel designer receptors have revolutionized the way neuroscientists can interrogate neural circuits. These new tools are being rapidly applied to many facets of neuroscience including the study of Parkinson's disease circuitry and therapies. This review highlights how optogenetics and designer receptors can be applied in the study of Parkinsonian dysfunction to understand the mechanisms behind motor and non-motor symptoms. We discuss how these tools have recently advanced our understanding of basal ganglia function and outline how they can be applied in future to refine existing treatments and generate novel therapeutic strategies for Parkinson's disease.

Chemogenetic silencing of the midline and intralaminar thalamus blocks amygdala-kindled seizures

“…Further refinement of viral targeting and infusion volumes will allow for selective targeting to sub-nuclei, with the added advantage of direct identification of the critical cell populations due to fluorescent labeling. The DREADD also approach avoids confounds associated with electrical stimulation, such as spreading activation with increasing current intensity, and more importantly spares activation of fibers of passage (Vazey and Aston-Jones, 2013). This latter issue is again, particularly important in the thalamus due to the diversity of tracts and projections.…”

Modulating Dopamine Signaling and Behavior with Chemogenetics: Concepts, Progress, and Challenges

“…In contrast to locomotor activity, which appears to be regulated predominantly by midbrain DA neurons projecting to ventral parts of the striatum, motor control and initiation of movement are more dependent on dorsal striatal DA neurotransmission. This is particularly evident in PD, where major symptoms include bradykinesia, akinesia, tremors, and movement rigidity (Vazey and Aston-Jones, 2013). These motor disabilities are associated with major loss of DAergic neurons within the SN, resulting in progressive loss of dorsostriatal DA input.…”

Chemical physics in living cells — Using light to visualize and control intracellular signal transduction

“…By controlling neuronal firing, optogenetics has provided a new way to investigate neuronal circuits in health and disease [68,69]. Currently, optogenetics has been used in basic and preclinical research on a wide spectrum of topics such as Parkinson's disease [70], sleep [71], cardiac function [72,73], neuropsychiatric diseases [74], epilepsy [75], and sight-restoring therapy [76,77]. Because there are extensive reviews on this topic, we will not expound on it in this work.…”