Abstract
Here we demonstrate a facile method by which to deliver complex spatiotemporal stimulation to neural networks in fast patterns, to trigger interesting forms of circuit-level plasticity in cortical areas. We present a complete platform by which patterns of electricity can be arbitrarily defined and distributed across a brain circuit, either simultaneously, asynchronously, or in complex patterns that can be easily designed and orchestrated with precise timing. Interfacing with acute slices of mouse cortex, we show that our system can be used to activate neurons at many locations and drive synaptic transmission in distributed patterns, and that this elicits new forms of plasticity that may not be observable via traditional methods, including interesting measurements of associational and sequence plasticity. Finally, we introduce an automated “network assay” for imaging activation and plasticity across a circuit. Spatiotemporal stimulation opens the door for high-throughput explorations of plasticity at the circuit level, and may provide a basis for new types of adaptive neural prosthetics.
Highlights
While brain networks are optimized for pattern detection, and organized by patterned activity (Sur and Rubenstein, 2005), methods for defining and delivering parallel stimulation patterns to multiple loci in neuronal networks using controlled experimental parameters have remained largely under-developed
We found that reliable spatiotemporal stimulation benefits from 3 components—software control for complex and composable stimulation, simple but principled stimulation electronics to quickly distribute the electricity to the right locations, and a real-time programmable digital intermediary between the two to enforce temporal precision and overcome the temporal jitter of standard computer operating systems
Analog Electronics for an Arbitrary Number of Stimulation Electrodes Any platform for spatiotemporal stimulation as a first step requires the control of an energy flux and the distribution of that flux
Summary
While brain networks are optimized for pattern detection, and organized by patterned activity (Sur and Rubenstein, 2005), methods for defining and delivering parallel stimulation patterns to multiple loci in neuronal networks using controlled experimental parameters have remained largely under-developed. Systems for stimulating many sites in a brain circuit in orchestrated spatiotemporal patterns have, for the most part, remained locked in the “one locus at a time” paradigm. To continue this shift toward network physiology at the circuit level, we sought. A growing number of neurological processes are believed to arise from the activation of single neurons or loci, but from the concerted interplay of neurons across a network (Pouget et al, 2000). It is known that engaging neurons at an appropriate “population” level via patterned sensory input will immediately re-define their responses (Engert et al, 2002) and re-sculpt network organization over time (Sharma et al, 2000), suggesting a rich repertoire of processes that make networks responsive to patterned input
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