Combining Optogenetics & Electrophysiology
Research from the University of Oxford, published in Neuron (Neuron 75, 58-64, July 12, 2012), has explored emerging theories that striatal dopamine (DA) function is not only driven by DA neurons but also by striatal cholinergic interneurons (Chls) directly affecting DA axons. This has important implications for understanding the role of axons versus soma in striatal DA pathways and may lead to wider re-evaluation of the role of different DA neuronal inputs.Striatal DA plays a critical role in regulation of motivation behaviour and motor function; therefore disruption to these DA pathways results in a range of addiction and motor disorders. A greater understanding of DA modulation would allow researchers to study alternative targeted drug therapies.
Cragg et al combined optogenetic activation with whole cell patch clamp recordings in striatal interneurons, whilst simultaneously detecting DA release and uptake using fast-scan cyclic voltammetry. This combination of techniques allowed them to precisely describe the neuronal events required for Chl-driven DA release. Their set-up included Scientifica's PatchStar micromanipulators, LBM-7 manual manipulator and motorised moveable top plate (MMTP). The integration of the motorised elements was optimised using Scientifica's free LinLab software allowing them to, effortlessly, carry out dual voltammetry and patch clamp recordings. They used Scientifica's unique "Follow Function" to navigate between areas of interest with multiple pipettes locked in the field of view.
Their data revealed that synchronised activity from Chls directly generates striatal DA release; confirming that "activity in the DA soma is not an exclusive trigger for axonal DA release". Further implications are that mediation of DA via Chl inputs is important for "conveying salience- or attention-related signals".
This study expertly incorporates a range of electrophysiology techniques and the increasingly popular method of optogenetic control; producing a compelling example of these complementary methods.