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Module 2 Local Field Potential Supratim Ray [email protected] References Buzsaki, Anastassiou and Koch, 2012, The origin of extracellular fields and currents – EEG, ECoG, LFP and Spikes, Nature Reviews Neuroscience Einevoll, Kayser, Logothetis and Panzeri, 2013, Modeling and analysis of local field potentials for studying the function of cortical circuits, Nature Reviews Neuroscience Local Field Potential - Outline Contributors Mainly Synaptic Activity Contribution from spikes, oscillations, AHP Spatial Spread ~250 micro-mm for uncorrelated activity increase when activity is correlated Relationship with Spikes Spike-related transients can be observed in the LFP above ~50 Hz and its contribution increases with increasing frequency Local field potential (LFP) Raw Signal Micro-electrode Spikes Local field Potential (LFP) LFP and other measures (EEG/ECoG) have fundamentally similar traces Figure 1, Buzsaki et al., 2012, Nature Reviews Neuroscience Contributors to the LFP Synaptic activity Spikes Intrinsic membrane oscillations Spike afterhyperpolarization (AHP) Neuronal Structure Figure 2-8, Kandel, Schwartz and Jessell Four functional regions - Input, Integrative, Conductile and Output Synaptic Transmission Wikipedia.org Synaptic activity Extracellular currents from many individual compartments must overlap in time to induce a measurable signal. Such overlap is easily achieved for relatively slow events, such as synaptic currents. The influx of cations from the extracellular into the intracellular space gives rise to a local extracellular sink. To achieve effective electroneutrality within the time constants of relevance for systems neuroscience, the extracellular sink needs to be 'balanced' by an extracellular source, that is, an opposing ionic flux from the intracellular to the extracellular space, along the neuron. Depending on the location of the sink current(s) and its distance from the source current(s), a dipole or a higher-order n-pole is formed. Buzsaki et al., 2012, Nature Reviews Neuroscience Modeling LFPs from trans-membrane currents Einevoll et al., 2013, Nature Reviews Neuroscience Pyramidal Cells Cells in the cortex form columns. In this image the red neurons, called pyramidal cells, are revealed to be entwined by blue fibers from other, inhhibitory neurons that slow their firing. The layers of the column are indicated by the numerals to the left: L1, at the surface of the brain, through L6, the deepest cortical layer. Pyramidal cells, which receive messages along their extensively branched fibers, and send long fibers out to other brain areas or down to the spinal cord, are crucial in movement control and in cognition. They have their cell bodies in layer 5 of the cortex, and the main receiving fiber, the apical dendrite, rises up to the surface, layer 1. ©BBP/EPFL http://biomedicalcomputationreview.org/ content/reverse-engineering-brain Synaptic activity Kajikawa and Schroeder, 2011, Neuron Fast action potentials Fast (Na+) action potentials generate the strongest currents across the neuronal membrane and can be detected as 'unit' or 'spike' activity in the extracellular medium. Although Na+ spikes generate large-amplitude deflections near the soma, until recently they were thought not to contribute substantially to the traditionally considered LFP band (<100 Hz) or to the scalp-recorded EEG because the strongest fields they generate are of short duration (<2 ms) and nearby neurons rarely fire synchronously in such short time windows under physiological conditions. However, synchronous action potentials from many neurons can contribute substantially to high-frequency components of the LFP. Buzsaki et al., 2012, Nature Reviews Neuroscience Calcium Spikes Other non-synaptic events that can contribute prominently to the extracellular field are the long-lasting (10–100 ms) Ca2+-mediated spikes. Because voltage-dependent regenerative Ca2+ spikes are often triggered by NMDA receptor-mediated excitatory postsynaptic potentials (EPSPs), separating them from EPSPs in extracellular recordings is not straightforward. Because dendritic Ca2+ spikes are large (10–50 mV) and long lasting, their share in the measured extracellular events can be substantial under certain circumstances. Buzsaki et al., 2012, Nature Reviews Neuroscience Membrane Oscillations Some voltage-gated currents contribute to intrinsic resonance and oscillation of the membrane potential. Several neuron types possess resonant properties. When intracellular depolarization is sufficiently strong, the resonant property of the membrane can give way to a self-sustained oscillation of the voltage. Voltage-dependent resonance and oscillations at theta frequency have been described in principal neurons of several cortical regions. By contrast, perisomatic inhibitory interneurons have a preferred resonance in the gamma frequency (30–90 Hz) range. To contribute substantially to the LFP, resonant membrane potential fluctuations must occur synchronously in nearby neurons, a feature that most often occurs in inhibitory interneurons. Buzsaki et al., 2012, Nature Reviews Neuroscience Spike afterhyperpolarization Elevation of the intracellular concentration of a certain ion may trigger influx of other ions through activation of ligand-gated channels, and this will in turn contribute to Ve. For example, bursts of fast spikes and associated dendritic Ca2+ spikes are often followed by hyperpolarization of the membrane, owing to activation of a Ca2+-mediated increase of K+ conductance in the somatic region. The amplitude and duration of such burst-induced afterhyperpolarizations (AHPs) can be as large (and last as long as) synaptic events, particularly when bursting of nearby neurons occurs in a temporally coordinated fashion. In the intact brain, responses to unexpected stimuli or movement initiation are often associated with relatively long-lasting (0.5–2 s) LFP shifts, which might be mediated by synchronized AHPs. Buzsaki et al., 2012, Nature Reviews Neuroscience Local Field Potential - Outline Contributors Mainly Synaptic Activity Contribution from spikes, oscillations, AHP Spatial Spread ~250 micro-mm for uncorrelated activity ncreases when activity is correlated Relationship with Spikes Spike-related transients can be observed in the LFP above ~50 Hz and its contribution increases with increasing frequency Local Field Potential - Outline Contributors – Mainly Synaptic Activity – Contribution from spikes, oscillations, AHP Spatial Spread ~250 micro-mm for uncorrelated activity ncreases when activity is correlated Relationship with Spikes Spike-related transients can be observed in the LFP above ~50 Hz and its contribution increases with increasing frequency Spatial Spread of LFP is a topic of much debate! 200-400 µm: Xing et al., Katzner et al., 2009 600-1000 µm: Berens et al., 2009 ~3 mm: Kreiman et al., 2006 several mm vertical: Kajikawa and Schroeder, 2011 LFP Spread (Katzner et al., 2009) V1, Anesthetized Cats Voltage Sensitive Dyes (VSD)+implanted microelectrodes Optimum integration radius: ~100 µm LFP Spread (Xing et al., 2009) V1, Anesthetized Monkeys Compared visual spreads of LFP and MUA LFP Spread = ~250 µm LFP Spread (Kajikawa and Schroeder, 2011) A1, awake monkeys LFP Spread (Kajikawa and Schroeder, 2011) Vertical spread observable at ~18 mm Volume conduction explains the large spread LFP Spread (Linden et al., 2011) The spatial reach of the LFP is activity dependent Spatial reach of local field potential is 200–300 μm with uncorrelated synapses For correlated synaptic inputs the reach is set by spatial extent of correlations In vivo-like network model mimicking sensory column is in correlated regime Correlated Uncorrelate d Local Field Potential - Outline Contributors – Mainly Synaptic Activity – Contribution from spikes, oscillations, AHP Spatial Spread ~250 micro-mm for uncorrelated activity ncreases when activity is correlated Relationship with Spikes Spike-related transients can be observed in the LFP above ~50 Hz and its contribution increases with increasing frequency Local Field Potential - Outline Contributors – Mainly Synaptic Activity – Contribution from spikes, oscillations, AHP Spatial Spread – ~250 micro-mm for uncorrelated activity – Increases when activity is correlated Relationship with Spikes Spike-related transients can be observed in the LFP above ~50 Hz and its contribution increases with increasing frequency LFP during stimulus presentation Firing rate Gamma rhythm Evoked LFP LFP during stimulus presentation Firing rate Gamma rhythm Evoked LFP LFP during stimulus presentation Firing rate Gamma rhythm Evoked LFP Compare spiking with LFP power at different frequencies Compare spiking with LFP power at different frequencies Firing rate Compare spiking with LFP power at different frequencies Firing rate Compare spiking with LFP power at different frequencies Firing rate Compare spiking with LFP power at different frequencies Firing rate Ray and Maunsell, PLoS Bio, 2011 high-gamma (>80 Hz) power is correlated with firing rate Ray and Maunsell, PLoS Bio, 2011 high-gamma (>80 Hz) power is correlated with firing rate Ray and Maunsell, PLoS Bio, 2011 high-gamma (>80 Hz) power is correlated with firing rate Trial-by-trial correlation STA analysis during spontaneous activity STA analysis during spontaneous activity STA analysis during spontaneous activity STA analysis during spontaneous activity STA analysis during spontaneous activity high-gamma (>80 Hz) power is correlated with firing rate Local Field Potential - Outline Contributors – Mainly Synaptic Activity – Contribution from spikes, oscillations, AHP Spatial Spread – ~250 micro-mm for uncorrelated activity – Increases when activity is correlated Relationship with Spikes Spike-related transients can be observed in the LFP above ~50 Hz and its contribution increases with increasing frequency Local Field Potential - Outline Contributors – Mainly Synaptic Activity – Contribution from spikes, oscillations, AHP Spatial Spread – ~250 micro-mm for uncorrelated activity – Increases when activity is correlated Relationship with Spikes – Spike-related transients can be observed in the LFP above ~50 Hz and its contribution increases with increasing frequency Rhythms of the brain Oscillations at different frequencies are often observed in brain signals The oscillations are associated with various cognitive states Brain signals obey a “1/f” power law: low frequency oscillations have large amplitude alpha hi-gamma/sigma http://www.scholarpedia.org/w/images/b/ba/Thalcortx_oscillations.gif Alpha Rhythm (8-12 Hz) Discovered by German neurologist Hans Berger, most famous for his invention of the EEG (Berger, 1929). This alpha activity is centered in the occipital lobe, and is presumed to originate there, although there has been recent speculation that it instead has a thalamic origin. The amplitude of alpha-frequency band activity in the human electroencephalogram is suppressed by eye opening, visual stimuli and visual scanning, and by attentive processing. An ‘idling’ rhythm that characterizes an alert-but-still brain state Recent studies have shown that there might be other alpha oscillations at different parts of the brain, associated with different functions. Stimulus/attention suppresses alpha rhythm Attend-out Pre-stimulus Attend-in Stimulation Frequency Frequency Fries et al., 2008, J Neurosci Gamma Oscillations (30-80 Hz) Discovered by Wolf Singer and colleagues in 1989. Neural assemblies oscillate at gamma frequencies (3080 Hz), such that the spiking activity of the neurons are synchronized. Binding by synchrony hypothesis Auto-correlation Cross-correlation Engel et al., 1991, PNAS Attention increases Gamma power and synchronization in higher visual areas (V4) Fries et al., 2008, J Neurosci