Mapping cortical mesoscopic networks of single spiking cortical or sub-cortical neurons

  1. Dongsheng Xiao
  2. Matthieu P Vanni
  3. Catalin C Mitelut
  4. Allen W Chan
  5. Jeffrey M LeDue
  6. Yicheng Xie
  7. Andrew CN Chen
  8. Nicholas V Swindale
  9. Timothy H Murphy  Is a corresponding author
  1. Kinsmen Laboratory of Neurological Research, Canada
  2. Beijing Institute for Brain Disorders, Capital Medical University, China
  3. Djavad Mowafaghian Centre for Brain Health, University of British Columbia, Canada
  4. University of British Columbia, Canada
13 figures, 5 videos and 1 table

Figures

Figure 1 with 2 supplements
Experimental setup and multichannel electrode recordings and spike classification.

(A) Set-up for simultaneous wide-field calcium imaging and single unit recording using a glass pipette or laminar silicon probe. (Bi) Top view of wide-field transcranial window and (ii) cortical …

https://doi.org/10.7554/eLife.19976.002
Figure 1—figure supplement 1
Spectral distribution of the spontaneous activity.

Average Fourier Transform (±SEM) of the resting state activity of green GCaMP6 fluorescence (black curve, n = 20) and green 532 nm reflectance (gray curve, n = 11) within barrel cortex of awake Ai93 …

https://doi.org/10.7554/eLife.19976.003
Figure 1—figure supplement 2
Deconvolution analysis of GCaMP data.

(A) Top: raw calcium image and time course of calcium dynamics in region of interest (ROI). Bottom: deconvolved calcium image and time course of deconvolved calcium dynamics ROI. (B) Top: …

https://doi.org/10.7554/eLife.19976.004
Sensitivity and specificity of STMs.

(A) Simultaneous calcium and spiking activity recording in GCaMP6f mouse and STM yielded from single unit recorded in barrel cortex. (B) Simultaneous GFP fluorescence and spiking activity recording …

https://doi.org/10.7554/eLife.19976.005
Figure 3 with 2 supplements
Topographic properties of cortical and thalamic STM.

(A) Electrode track for each recording (Blue channel: DAPI, yellow: DiI). (B) STM and overlay contours of neurons recorded in barrel cortex in the same animal. Each color represents one STM contour. …

https://doi.org/10.7554/eLife.19976.006
Figure 3—figure supplement 1
STMs were computed at different depths of the electrode using single cell spikes, Multi-Unit-Activity (MUA) and local field potential (LFP) amplitude.

Single unit STMs were computed (see Materials and methods) for up to three representative cells at each depth. MUA STMs at each electrode were computed using all spiking activity over a threshold (>4…

https://doi.org/10.7554/eLife.19976.007
Figure 3—figure supplement 2
Thalamic STMs: Spike vs LFP.

STMs were computed at different depths of the electrode using single cell spikes, Multi-Unit-Activity (MUA) and LFP amplitude (See Figure 3—figure supplement 1). In contrast to cortical STMs, single …

https://doi.org/10.7554/eLife.19976.008
STM compared with seed pixel correlation maps (SPM).

(A) Cortical STM (left) and the best fitting SPM (right) according to correlation coefficient (cc) values for different electrode placements (text to the left of panel). Similarity was calculated by …

https://doi.org/10.7554/eLife.19976.010
Examples of STMs and projection maps.

(A) Example of STMs from neurons recorded in BCS1, VPM, VPL, HPF and CP. (B) Example of projection maps (2D surface and 3D) reconstructed from Allen Brain Atlas with injection sites (Oh et al., 2014)…

https://doi.org/10.7554/eLife.19976.011
Figure 6 with 6 supplements
Montages of cortical and thalamic spatio-temporal dynamics.

(A) Top: right hemisphere barrel cortex neuron spiking time montage stereotyped dynamics in left hemisphere barrel cortex region-of-interest (ROI). The maximally activated pixel in the ROI (red …

https://doi.org/10.7554/eLife.19976.012
Figure 6—figure supplement 1
Single-cell STM and STMTDs are similar across spiking modes.

(Ai, Bi) Cortical cell spiking modes determined by grouping the distribution of each spike’s inter-spike-interval between previous (x-axis) and following (y-axis) spike. The four quadrants indicate …

https://doi.org/10.7554/eLife.19976.013
Figure 6—figure supplement 2
Cortical cell STM and STMTDs are similar across spiking modes.

Left: Spatio-temporal motifs for the three cortical cells presented in Figure 6 considering contributions of all spikes from each cell (top motif) versus just the bursting condition for each cell …

https://doi.org/10.7554/eLife.19976.014
Figure 6—figure supplement 3
Thalamic cell STM and STMTDs are similar across spiking modes.

Left: Spatio-temporal motifs for the three of the four cortical cells presented in Figure 6 considering contributions of all spikes from each cell (top motif) vs. just the bursting condition for …

https://doi.org/10.7554/eLife.19976.015
Figure 6—figure supplement 4
Single spike motifs sub-grouping reveals similar STMs across sub-networks.

(A) Five examples of STMs generated from a single spike from a cell reveal substantial variability and high activation (ΔF/F0 >10% for some spikes). (B) Distribution of all single spike STMs (3779 …

https://doi.org/10.7554/eLife.19976.016
Figure 6—figure supplement 5
Additional examples of single cells STM stability in other mice and for larger partition sizes.

(A) Two examples of single cortical cell STMs recovered from sub-networks: (i) four spike-triggered sub-network STMs; (ii) spontaneous sub-network STMs; (iii) difference between cell-triggered and …

https://doi.org/10.7554/eLife.19976.017
Figure 6—figure supplement 6
Spike-triggered variance map.

(A) Spatiotemporal dynamic of spike-triggered average map of a cortical neuron. The time window is from −3s to 3s. (B) Spatiotemporal dynamic of spike-triggered variance map of the same neuron. The …

https://doi.org/10.7554/eLife.19976.018
Figure 7 with 1 supplement
Classification of STMTD patterns.

(A) Example of two STMTDs from pixels within L-BCS1 (left barrel cortex) from a single mouse recording (both cortical and subcortical neurons STMTD pixel locations shown). Each recorded cell STMTD …

https://doi.org/10.7554/eLife.19976.019
Figure 7—source data 1

Data files for PCA distribution clusters.

This zip archive contains all original STMTDs (*traces.txt files) from cortical cells (220) and subcortical cells (208) used in generating Figure 7B. The STMTDs are interpolated to 100 Hz (i.e. 600 time points for each cell for a 6 s period). The archive also contains (3D) coordinates from PCA distributions of the traces (*scatter.txt files) which are displayed in Figure 7B. Both traces and PCA coordinates can be viewed independently.

https://doi.org/10.7554/eLife.19976.020
Figure 7—figure supplement 1
Limited contribution of blood artifacts on STA.

(A) Diagram of the experimental setup used to evaluate the contribution of blood volume to the GCaMP green fluorescence. Local blood volume was evaluated by measuring the change in short blue (447 …

https://doi.org/10.7554/eLife.19976.021
Figure 8 with 1 supplement
Spatiotemporal patterns of STMs.

(A) Top: Normalized STMTDs (as in Figure 7) from maximum pixels tracked in multiple ROIs (HLS1, FLS1, BCS1, RS, V1, M1, PTA and ACC, see Table 1) for 255 cortical cells. Each horizontal line …

https://doi.org/10.7554/eLife.19976.022
Figure 8—figure supplement 1
Limited contribution of body movement on STA.

(A) Image insets: pictures of the frame average and standard deviation showing the location of movement over one entire recording. Yellow box: region of interest used to quantify movement. Graph:

https://doi.org/10.7554/eLife.19976.023
Author response image 1
Temporal and spectral signatures of spontaneous and epileptic events measured from the local field potential (LFP).

(A) Top (black trace), 100s segment of LFP recording of spontaneous activity from superficial layer of cortex. Bottom, spectrogram (Morlet-wavelet scalograms) of the LFP trace. (B) Top (black …

https://doi.org/10.7554/eLife.19976.029
Author response image 2
Spike-triggered variance map.
https://doi.org/10.7554/eLife.19976.030
Author response image 3
Spike Triggered Covariance Analysis of BCS1 Neuron.

(A) Each calcium image was recorded each Δt = 33.33 ms (frame rate = 30 Hz), and the spikes recorded in BCS1 neuron were binned within the same interval. In this example, we recorded 15250 frames …

https://doi.org/10.7554/eLife.19976.031
Author response image 4
Spike Triggered Covariance Analysis of sub-cortical Neuron.

(A) a1. STA of this sub-cortical neuron shows unique spatiotemporal pattern. a2. Distribution of underlying calcium image matrix projected on STA of this sub-cortical neuron. a3. The input/output …

https://doi.org/10.7554/eLife.19976.032
Author response image 5
Running median and random spike normalization.

(A) STA from real spikes (1st line), random spikes (2nd line) and real spikes after running median filtering (3rd line). 4th and 5th lines are subtractions of STA by random spikes and running median …

https://doi.org/10.7554/eLife.19976.033

Videos

Video 1
Cortical neuron-triggered bilateral mesoscale calcium activity.

Left: dorsal cortex calcium dynamics triggered from a right hemisphere barrel cortex recorded cell. Right, time-course reflecting dynamics in the left hemisphere barrel cortex (green) alongside a …

https://doi.org/10.7554/eLife.19976.024
Video 2
Thalamic neuron #1 triggered bilateral mesoscale calcium activity.

As in Video 1 but from a right-hemisphere thalamic neuron. Region-of-interest (green) in the left hemisphere exhibits a transient pre-spiking depression followed by activation correlating with spike …

https://doi.org/10.7554/eLife.19976.025
Video 3
Thalamic neuron #2 triggered bilateral mesoscale calcium activity.

As in Video 2 but from another thalamic neuron revealing peak activation in a different region-of-interest.

https://doi.org/10.7554/eLife.19976.026
Video 4
Thalamic neuron #3 triggered bilateral mesoscale calcium activity.

As in Video 2. Depressed cortical calcium activity is present in the left hemisphere barrel cortex region-of-interest prior to spiking and persists for an additional 2 s.

https://doi.org/10.7554/eLife.19976.027
Video 5
Evaluation of whisker movement.

Left: Average of absolute gradient within the region of interest (yellow box in Figure 8—figure supplement 1) between the frames 3400 and 5000. Right: Corresponding image frames displayed at real …

https://doi.org/10.7554/eLife.19976.028

Tables

Table 1

Abbreviation used to define different cortical/sub-cortical areas.

https://doi.org/10.7554/eLife.19976.009

S1

Primary somatosensory area

S2

Supplemental or Secondary Somatosensory area

FL

Forelimb region of the Primary Somatosensory area (FLS1)

HL

Hindlimb region of the Primary Somatosensory area (HLS1)

BC

Barrel region of the Primary Somatosensory area (BCS1)

M1

Primary motor area

M2

Secondary motor area

MO

Mouth region of the Primary Somatosensory area

NO

Nose region of the Primary Somatosensory area

TR

Trunk region of the Primary Somatosensory area

UN

(Unassigned) region of the Primary Somatosensory area (S1)

AC

Anterior Cingulate area (ACC)

A

Anterior or Posterior Partial Association areas: PTLp or PTA

V1

Primary visual cortex

AL

AnteroLateral regions of the extrastriate visual areas

AM

AnteroMedial regions of the extrastriate visual areas

LM

LateralMedial regions of the extrastriate visual areas

PL

PosteroLateral regions of the extrastriate visual areas

LI

LateralIntermediate regions of the extrastriate visual areas

PM

PosteroMedial regions of the extrastriate visual areas

POR

Postrhinal regions of the extrastriate visual areas

RL

RostroLateral regions of the extrastriate visual areas

AU

Primary Auditory area

TEA

Temporal Association area

RS

Retrosplenial area

PTA

Parietal Association area

VPM

Ventral posteromedial nucleus of the thalamus

VPL

Ventral posterolateral nucleus of the thalamus

PO

Posterior complex of the thalamus

RT

Reticular nucleus of the thalamus

LGN

Lateral geniculate nucleus

CP

Caudoputamen

HPF

Hippocampal formation

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