Dopamine Neuron-Specific Optogenetic Stimulation in Rhesus Macaques

Abstract

SummaryOptogenetic studies in mice have revealed new relationships between well-defined neurons and brain functions. However, there are currently no means to achieve the same cell-type specificity in monkeys, which possess an expanded behavioral repertoire and closer anatomical homology to humans. Here, we present a resource for cell-type-specific channelrhodopsin expression in Rhesus monkeys and apply this technique to modulate dopamine activity and monkey choice behavior. These data show that two viral vectors label dopamine neurons with greater than 95% specificity. Infected neurons were activated by light pulses, indicating functional expression. The addition of optical stimulation to reward outcomes promoted the learning of reward-predicting stimuli at the neuronal and behavioral level. Together, these results demonstrate the feasibility of effective and selective stimulation of dopamine neurons in non-human primates and a resource that could be applied to other cell types in the monkey brain.

Therapeutic Potential of Optogenetic Treatment for Individuals with Multiple Sclerosis

“…This process is thoroughly described in the study by Stauffer et al (2016). Applying photostimulation to the regions found to underlie tremor development and motor dysfunction in MS, such as gait, would be a feasible means of treating these symptoms, given its documented applications in similar cases (Kravitz et al, 2010).…”

“…Celebrating 20 years of undergraduate research (Stauffer et al, 2016;Tønnesen, 2013). This process is thoroughly described in the study by Stauffer et al (2016).…”

“…A vector delivering Cre recombinase under the control of a tyrosine hydroxylase (TH) promoter fragment and a vector delivering a Cre-recombinase-dependent ChR2 were mixed and injected to attain cell-type-specific expression of ChR2 (Stauffer et al, 2016). The TH promoter can be substituted in the first vector to other neuron-subtype-specific promoters to optogenetically control other neuron types in a monkey brain.…”

“…successful cell-type-specific expression of ChR2 in midbrain dopamine neurons of wild-type Rhesus macaques utilized AAVs, not LVs (Stauffer et al, 2016). A vector delivering Cre recombinase under the control of a tyrosine hydroxylase (TH) promoter fragment and a vector delivering a Cre-recombinase-dependent ChR2 were mixed and injected to attain cell-type-specific expression of ChR2 (Stauffer et al, 2016).…”

Viral-mediated optogenetic stimulation of peripheral motor nerves in non-human primates

“…Indeed, even the development of optogenetic techniques for NHPs in the central nervous system (CNS) has proven challenging with examples of successful viral transduction studies slowly beginning to accumulate [27][28][29][30][31][32][33]. A handful of studies have demonstrated viral transduction of peripheral neuromuscular tissue with fluorescent proteins in NHP models [34,35], but optogenetic modulation of peripheral neural activity in primates similar to the aforementioned rodent studies has not been reported to date.…”