Fig. 4: Emergence and dysfunction of β-events.
A Potential mechanism of narrow-band beta LFP information flow. Beta LFP is modulated by deep layer cortical activity via feedback while gamma dominates in superficial layer via feedforward inputs. B Example response of beta/gamma LFP power during voluntary running in monomeric versus αSyn PFF animals. C Filtered beta LFP across velocity triggered trials. Blue traces correspond to putative bursts of beta transients with compiled waveforms of β-events (n = 11 trials). D Examples of peristimulus beta band activity across two trials. Asterisks mark detected β-event waveforms. E Exemplar β-event spectrogram. F β-event amplitude and duration in representative recording of one monomer mouse (n = 992 events). G, H Z-scored β-event amplitude compared to monomeric control animals (indicated by gray box) across depth and pathological timeline for cortical seeded mice (G) FsupMon*PFF (5, 20) = 8.78, p = 3.15 × 10−7, FdeepMon*PFF (5, 20) = 13.11, p = 8.76 × 10−11 and striatal seeded mice (H) FsupMon*PFF (5, 18) = 6.78, p = 0.0002, FdeepMon*PFF (5, 18) = 7.04, p = 0.0002 (*p < 0.01, **p < 0.001, ***p < 0.0001, two-way unbalanced ANOVA with Bonferroni correction); Cortically seeded: 1242 ± 302 β-events per animal per timepoint. n = 22 cortically injected mice in total. Cortical monomer n = 4 mice (2 mice at 2 wpi and 2 mice at 12 wpi), Cortical PFF mice n = 18 mice (3, 4, 4, 3, 4 animals across each 2-week time point, i.e. every 2 weeks starting at week 2 and ending at week 12, respectively). Striatally seeded: 1312 ± 401 β-events per animal per timepoint. n = 20 striatally injected mice in total, Striatal monomer n = 4 mice (2 mice at 2 wpi and 2 mice at 12 wpi), Striatal PFF mice n = 16 mice (3, 3, 3, 3, 4 PFF animals across each 2-week time point, i.e. every 2 weeks starting at week 2 and ending at week 12, respectively), wpi weeks post-injection, data shown as median with first and third quartiles. I Histogram distribution of β-event duration and number of events per trial across weeks for cortical (top) and striatal (bottom) seeded mice. Dashed line indicates significance in distribution compared to shuffled surrogates. Distribution of beta power and duration show high variability of β-event behavior. J Schematic of proposed emerging changes in narrow-band beta LFP dynamics. Aberrant deep layer beta dynamics may drive superficial beta dynamics via feedback (left). Normalized amplitude of β-event profiles for two example mice of cortically seeded (top) and striatally seeded (bottom) with corresponding depth. K Experimental schematic of dual LFP-Intracellular recordings (right). Intracellular recording from putative L5 and L2/3 pyramidal neurons in primary motor cortex (top trace). Wideband filtered LFP (4–40 Hz) (bottom trace). L LFP beta spectrogram and spiking response of L5 and L2/3 pyramidal neuron. Detected β-events is noted by white asterisk. M Vm and extracellular β-event -triggered coherence for L2/3 and L5 pyramidal neurons. (n = 10 neurons, 7 L5 neurons, 3 L2/3 neurons, p = 0.00045, ***p < 0.0005, one-sided Kruskal-Wallis, data shown on box plots with 25th, median and 75th percentiles and with whiskers indicating min and max values). N Extracellular β-event triggered subthreshold response of L5 and L2/3. Average β-event waveform (dash line), average subthreshold response from L5 pyramidal neurons (blue trace), n = 7 neurons, and subthreshold response to layer 2/3 neurons (black trace, n = 3 neurons). O β-event triggered AP bursting probability from L5 and L2/3 pyramidal neurons (N = 2406 β-events across 243 trials, p = 5.5 × 10−45, Kruskal-Wallis). P Intracellular-frequency response during bursting of L5 pyramidal neuron.
