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H2020 STARDUST Project in Brief

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H2020 STARDUST Project in Brief Implantable neural recording technologies Fabian Kloosterman 14/5/20 In vivo optogeneticS, elecTrophysiology and phArmacology with an ultRasonically-powered DUST for Parkinson's Disease This project has received funding from the European Union’s Horizon 2020 research and innovation programme under grant agreement no 767092. The brain is a complex machine that supports sensation, behavior and cognition thought feeding external world (senses) perception planning communication language locomotion internal milieu learning & instincts memory navigation The human brain: • contains ~100 billion (1011) computational units (neurons) • and ~1 quadrillion (1015) interconnections (synapses) • but only consumes ~20 W energy In vivo optogeneticS, elecTrophysiology and phArmacology with an ultRasonically-powered DUST for Parkinson's Disease The burden of brain disorders traumatic brain injury stroke epilepsy tourette syndrome In 2010 in Europe : anxiety disorders ADHD 380 million diagnoses bipolar disorder dyslexia € 295 billion direct costs post-traumatic stress € 186 billion non-medical costs brain tumor schizophrenia € 315 billion indirect costs amyotrophic lateral sclerosis € 798 billion total addiction depression autism multiple sclerosis parkinson huntington In vivo optogeneticS, elecTrophysiology and phArmacology with an ultRasonically-powered DUST for Parkinson's Disease The challenges of studying the brain: large spatial and temporal scales (Scientific American, 2013) 1 - 100 ms Neural activity < 1 um – Molecular ~10 um – Cellular 1 - 100 s Short-term memory ~1 mm – Network 1 day Sleep-wake cycle years Long-term memory Plasticity decades Development / Life cycle ~1 cm – System > 1 cm – Whole brain In vivo optogeneticS, elecTrophysiology and phArmacology with an ultRasonically-powered DUST for Parkinson's Disease The neuron The brain is made up of individual units (neurons) that contain specialized features such as dendrites, a cell body, and an axon. Neurons are specialized cells that differ in size, shape, and structure according to their location or functional specialization. (Luo, Principles of Neurobiology, Ch 1) In vivo optogeneticS, elecTrophysiology and phArmacology with an ultRasonically-powered DUST for Parkinson's Disease Synapses Neurons are connected by sites of contact (synapses). Generally, in a synapse the axon terminal of one neuron is juxtaposed to the dendrite of another neuron. (Luo, Principles of Neurobiology, Ch 1) In vivo optogeneticS, elecTrophysiology and phArmacology with an ultRasonically-powered DUST for Parkinson's Disease Neuronal communication: electrical and chemical In response to input, neurons generate all-or- none electrical signals (action potentials) that travel along the axon to synapses. At the synapse, the action potentials induces release of chemical neurotransmitters that bind to receptors on the downstream neuron and change the intracellular electrical potential. http://www2.fz-juelich.de/isb/isb-1//GPCR With sufficiently strong input, the downstream neuron will generate its own action potential. In vivo optogeneticS, elecTrophysiology and phArmacology with an ultRasonically-powered DUST for Parkinson's Disease Excitatory and inhibitory neurotransmission Depending on the neurotransmitter released at the synapse and the receptor type on the postsynaptic neuron, the result of the signaling is either excitatory post-synaptic potentials (EPSP) or inhibitory post- synaptic potential (IPSP). Most neurons in the brain are excitatory, while a very diverse subset (~20%) of neurons are inhibitory. Kandel et al. Principles of Neural Science, Ch 12 In vivo optogeneticS, elecTrophysiology and phArmacology with an ultRasonically-powered DUST for Parkinson's Disease Synaptic inputs integrate in space and time Postsynaptic potentials summate in time, when a second synaptic activation occurs before the first one is over. Postsynaptic potentials summate in space, when a two neighboring synapses are activated. Kandel et al. Principles of Neural Science, Ch 12 In vivo optogeneticS, elecTrophysiology and phArmacology with an ultRasonically-powered DUST for Parkinson's Disease Summary of neural signaling Excitatory post-synaptic potentials trigger an action potential if they exceed the threshold at the axon initial segment (trigger zone). The action potential threshold is high in the dendrite and only with strong synaptic input can a dendritic spike be initiated. Kandel et al. Principles of Neural Science, Ch 12 In vivo optogeneticS, elecTrophysiology and phArmacology with an ultRasonically-powered DUST for Parkinson's Disease A multitude of invasive and non-invasive techniques exist to measure neural activity Gazzaniga et al., 2009 In vivo optogeneticS, elecTrophysiology and phArmacology with an ultRasonically-powered DUST for Parkinson's Disease Extracellular potentials: local field potentials (LFP) and spikes Fast, localized potentials in the hippocampal cell layer represent action potentials (spikes) generated by individual neurons Slow potentials (LFP) represent the summed activity of a large population of neurons https://www.cambridgeneurotech.com/neural-probes Data courtesy of John Wolf, Universoty of Pennsylvania, USA In vivo optogeneticS, elecTrophysiology and phArmacology with an ultRasonically-powered DUST for Parkinson's Disease Extracellular potentials are a macroscopic reflection of transmembrane currents negative potential field positive potential field current source current sink current source (Leung, 2010) In vivo optogeneticS, elecTrophysiology and phArmacology with an ultRasonically-powered DUST for Parkinson's Disease Properties of extracellular potentials • Superposition principle: total current density and potential field is a sum of the current densities and potential fields of each of the current sources separately. • Cancelation: spatial overlap of current sinks and sources results in cancelation; thus spatial segregation is necessary to be able to measure potentials macroscopically • Volume conduction: extracellular potentials decrease with distance, but are still measurable at a distance from the current sources/sinks The polarity and magnitude of extracellular potentials depends on the spatial distribution of current sinks/sources at any given time In vivo optogeneticS, elecTrophysiology and phArmacology with an ultRasonically-powered DUST for Parkinson's Disease Spike sorting Single electrodes pick up the spiking activity of multiple neighboring neurons. Spike amplitude and waveform change as a function of the electrode’s position relative to neuron. By using multiple closely positioned electrodes that measure slightly different versions of the same signals, spikes can be classified as coming from the same neuronal source (spike sorting). (Buzsaki et al., 2012) In vivo optogeneticS, elecTrophysiology and phArmacology with an ultRasonically-powered DUST for Parkinson's Disease Spike sorting Example analysis pipeline for spike sorting. First, the local field potentials and spikes are separated using digital filters. Second, spikes are detected and clustered based on their features. Finally, a manual curation step is performed to exclude noise and multi-neuron clusters. (Gonzalo Rey et al., 2015) In vivo optogeneticS, elecTrophysiology and phArmacology with an ultRasonically-powered DUST for Parkinson's Disease Rey et al., 2015 Neuropixels: state-of-the-art high-density probes Jun et al. Nature 551, 232–236 (2017) doi:10.1038/nature24636 In vivo optogeneticS, elecTrophysiology and phArmacology with an ultRasonically-powered DUST for Parkinson's Disease Future: miniature wireless devices (neural dust) (Seo et al., 2013; Neely et al., 2018) In vivo optogeneticS, elecTrophysiology and phArmacology with an ultRasonically-powered DUST for Parkinson's Disease Thank you Fabian Kloosterman ([email protected]) www.project-stardust.eu ; Project coordinator: Farshad Moradi [email protected] In vivo optogeneticS, elecTrophysiology and phArmacology with an ultRasonically-powered DUST for Parkinson's Disease.
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