Kristin Sellers PhD Department of Neurological Surgery University of California San Francisco All coursework for a neuroscience PhDand some more in 1 hour Concepts capabilities and techniques ID: 1046921
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1. Modern Neuroscience: An Overview of Measurement and Analysis of Neural ActivityKristin Sellers, PhDDepartment of Neurological SurgeryUniversity of California, San Francisco
2. All coursework for a neuroscience PhD…and some more… in 1 hourConcepts, capabilities, and techniquesThe biased perspective of an electrophysiologistWhat this is:The full storyAn equal explanation of all measurement capabilitiesAn equal discussion of all cells in the brain (sorry glia)The nitty gritty (e.g. no circuit diagram models of neurons)What this is not:Komendantov & Canavier, 2002Buzsaki et al, 2012, Nature Reviews Neuroscience
3. A brief aside: Model systemsCryan & Holmes, 2005, Nature Reviews Drug DiscoveryWhy do we use model systems?EthicsCostConvenience (e.g. animal life cycle)Experimental manipulationIntroduction of foreign biologics (DNA from other animals, etc)
4. Today’s Discussion Topics:Measuring brain structureMeasuring brain functionPhysiology underlying measured brain functionTrue vs measured activityNetwork activity
5. StructureCentral Nervous System (CNS): Brain and spinal cordPeripheral Nervous System (PNS): Somatic and autonomic nervous systemsNeurons: dendrites (input), cell body, axons (output)
6. Measuring Brain StructureMRICTElectron MicroscopyStaining (Golgi)Staining (Immunohistochemistry fluorescence)Post-Mortem Dissection
7. Zhou et al, NeuroImage, 2016Measuring More Brain StructureSellers et al, Cell Reports, 2016Staining (Nissl)Tracing
8. FunctionIntracellular signaling and intercellular singlingChemical: NeurotransmittersElectrical: Movement of charged ions across a membrane potentialChanges in membrane permeability to ions[Here’s where “not the whole story” comes in – skipping metabotropic receptors, gap junctions, and a lot more]
9. Measuring Brain Function in AnimalsHofer et al, 2011Calcium ImagingFast-scan cyclic voltammetryIntracellular and Extracellular Electrophysiology
10. ECoGEEGPETfNIRSfMRIMeasuring Brain Function in HumansMEGSPECT
11. Physiology underlying measured brain functionNa+Ca2+K+Cl-Inside of neuron(net negative charge) Outside of neuron Na+Na+Na+Na+Na+Cl-Cl-K+K+K+K+A-A-A-A-A-Concentration Gradients:Na+Cl-K+??
12. Action Potentials
13. EPSP: Graded depolarization that moves the membrane potential closer to the threshold for firing an action potentialIPSP: Graded hyperpolarization that moves the membrane potential further from the threshold for firing an action potentialNeurons can receive as many as 200,000 terminals -- many EPSPs and IPSPs – relative timing can affect if an action potential occursKa Xiong Charand
14. So what am I recording?Local Field Potential (LFP)‘Spikes’ (putative action potentials)time
15. Recording parameters affect your data!Nyquist rate = Minimum sampling rate required to prevent aliasing of a signal (2*highest frequency of interest)In practice, better to use 5 to 10x Nyquist rateLFP = [0.5 200Hz]Fs > 1kHzSpiking dataFs > 20kHz
16. But is what I’m recording actually brain activity?Signal vs noiseLine noise: 60Hz (US/Canada), 50Hz (Europe)Movement artifactMost electrophysiology is done with referential recordings – what is used as reference?
17. Time-Frequency DomainFourier TransformBandpass filter / Hilbert TransformWavelet TransformMulti-taper methodDelta: 0.5 – 4 HzTheta: 4 – 8 HzAlpha: 8 – 12 HzBeta: 12 – 30 HzGamma: 30 – 50 HzBlue = Sine wavesBlack = Band-pass filtered LFP traces
18. Spectrum (Amplitude / Power)Phase Locking (Phase)Spectral measures of interestSpectrograms (Power across time)AwakeAnesthetized
19. ECoG ChannelsECoG ChannelsCoherence between Chan A and Chan B60Hz noiseNoise harmonicsPhysiologically meaningfulLikely not physiologically meaningfulNetwork Dynamics: Functional ConnectivityCoherence: Analogous to frequency-specific correlation between signals
20. Proposed Network: Compilation from many studiesBaluch & Itti, 2011Brain structures likely involved in attentional processing. Determined through microstimulation and lesion studies.Summary of ~50 studies conducted in NHP.
21. Bullmore & Sporns, 2009Structural and Functional Brain Networks: Graph TheoryEstimate a continuous measure of association between node (e.g. spectral coherence, mutual information, Granger causality, correlations structural metrics).Generate an association matrix and apply a threshold to produce a binary adjacency matrix.Compare resulting network parameters with the null distribution (equivalent parameters estimated in a random network)