Abstract
Genetically encoded voltage indicators (GEVIs) expressed pan-neuronally were able to optically resolve bicuculline induced spontaneous oscillations in brain slices of the mouse motor cortex. Three GEVIs were used that differ in their timing of response to voltage transients as well as in their voltage ranges. The duration, number of cycles, and frequency of the recorded oscillations reflected the characteristics of each GEVI used. Multiple oscillations imaged in the same slice never originated at the same location, indicating the lack of a “hot spot” for induction of the voltage changes. Comparison of pan-neuronal, Ca2+/calmodulin-dependent protein kinase II α restricted, and parvalbumin restricted GEVI expression revealed distinct profiles for the excitatory and inhibitory cells in the spontaneous oscillations of the motor cortex. Resolving voltage fluctuations across space, time, and cell types with GEVIs represent a powerful approach to dissecting neuronal circuit activity.
Highlights
Arising from targeted surgical lesioning technique to alleviate various intractable neurological symptoms, deep brain stimulation (DBS) has developed over the years to treat Parkinson’s disease (PD), dystonia, epilepsy, cluster headache, memory loss, obsessive-compulsive disorder, Tourette syndrome (TS), as well as depression (Benabid et al, 1987, 2009; Lozano and Hamani, 2004; Bernstein and Peters, 2005)
By targeting expression of a Genetically encoded voltage indicators (GEVIs) to CaMKIIα+ pyramidal cells or to PV+ inhibitory interneurons, we further explored whether or not we could derive any meaningful insight into each specific cell type’s role in generating oscillations in the motor cortex
The results presented here demonstrate that ArcLight family of GEVIs should be able to monitor the effects of DBS on the motor cortex
Summary
Arising from targeted surgical lesioning technique to alleviate various intractable neurological symptoms, deep brain stimulation (DBS) has developed over the years to treat Parkinson’s disease (PD), dystonia, epilepsy, cluster headache, memory loss, obsessive-compulsive disorder, Tourette syndrome (TS), as well as depression (Benabid et al, 1987, 2009; Lozano and Hamani, 2004; Bernstein and Peters, 2005). Despite the fact that DBS is almost 30 years old, how deep brain stimulation works to ameliorate such diverse neurological disorders is still unknown. Having an optical readout of activity from different components of neuronal circuits affected by DBS would help explain the therapeutic mechanism leading to improved clinical outcomes. Being able to monitor both activation and inhibition is critical for such ailments as PD and TS since the balance between these two types of activities has been altered
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