How many neurons are sufficient for perception of cortical activity?

  1. Henry WP Dalgleish
  2. Lloyd E Russell
  3. Adam M Packer
  4. Arnd Roth
  5. Oliver M Gauld
  6. Francesca Greenstreet
  7. Emmett J Thompson
  8. Michael Häusser  Is a corresponding author
  1. Wolfson Institute for Biomedical Research, University College London, United Kingdom
4 figures and 1 additional file

Figures

Figure 1 with 6 supplements
Driving behaviour with two-photon optogenetics targeted to ensembles of neurons in L2/3 barrel cortex.

(a) Schematic of all-optical setup. Bottom left: Example of flexible ensemble photostimulation. Three 10 neuron groups in barrel cortex (red, green, blue circles joined by group centroids) were …

Figure 1—figure supplement 1
Indicator and opsin expression overlap analysis.

(a) Detection of indicator/opsin expression overlap. Suite2P followed by manual curation was used to detect functional GCaMP-expressing neurons from time-series data (top row) and Cellpose followed …

Figure 1—figure supplement 2
Spatial resolution of spiral-scanned two-photon optogenetic activation of Kv2.1-C1V1.

(a) Left: A cross-shaped grid of photostimulation targets was centred on a single target neuron and each photostimulation target was activated 10 times in random order (10 µm inter-target distance, …

Figure 1—figure supplement 3
1P training protocol.

(a) Typical training protocol to transition a naïve mouse to being able to detect two-photon stimulation via a series of one-photon priming phases. Note that exact duration of each component varied …

Figure 1—figure supplement 4
Example pre-training selection and mapping of 200 neurons in L2/3 barrel cortex.

(a) Kv21-C1V1-mScarlet expression from an example four-plane imaging volume with stimulation targets overlaid in pink. Neurons are chosen arbitrarily, with the only criteria being that neurons are …

Figure 1—figure supplement 5
Rapid transfer learning from 1P to 2P optogenetic stimuli.

(a – b) Response rates for different 1P and 2P stimulus types from the first session using 2P stimuli, quantified as proportion of trials where animal licked (a) and d-prime relative to catch trials …

Figure 1—figure supplement 6
Comparison of behavioural response to somatic and non-somatic C1V1.

(a) Animals detect stimulation of somatic and non-somatic C1V1 to similar extents. (b) Animals respond slightly quicker to stimulation of non-somatic C1V1. (c) Reaction times are similarly …

Figure 2 with 3 supplements
Animals detect the targeted activation of tens of neurons.

(a) Example imaging volumes from an experiment showing 200 (top), 50 (middle) and 5 (bottom) targeted C1V1-expressing neurons. (b) Example lick raster concatenating an animal’s two psychometric …

Figure 2—figure supplement 1
Quantification of neuronal responses.

(a) Example target zones. Left: section of a plane in a volumetric FOV showing Suite2P ROIs (coloured regions), Suite2P centroids (black dots), target co-ordinates (pink dots) and lateral extent of …

Figure 2—figure supplement 2
Reaction time standard deviation, but not mean, scales with the number of target neurons activated.

(a–b) Relationship between mean (a) and standard deviation (b) of reaction time and the number of activated target neurons.

Figure 2—figure supplement 3
Detection of small ensembles of neurons improves across days irrespective of whether the same neurons were targeted.

(a) FOV from training sessions across 3 consecutive days where we stimulated the same 30 neurons each day. (b) Average behavioural response rates for 100 neuron, 30 neuron and catch trial conditions …

Figure 3 with 3 supplements
Increasing target activation is matched by background network suppression.

(a) The proportion of neurons activated across all neurons (targets and background) increases as more target neurons are activated. Inset right: average activation across all trial types is …

Figure 3—figure supplement 1
Comparison of network activity on hits and misses for both threshold go trials and catch trials in an effort to quantify and account for lick responses.

(a) The proportion of background neurons activated when different numbers of target neurons are activated on hits/false alarms (green) and misses/correct rejects (grey) on stimulus trials (error …

Figure 3—figure supplement 2
Neuropil subtraction has a small effect on response amplitude but it is not the sole cause of negative going responses.

(a) Distribution of trial-wise responses on 50+ neuron stimulation trials calculated from raw (Raw; black) and neuropil subtracted (Sub; red) traces (N = 30,894 neurons, 1312 trials). A large …

Figure 3—figure supplement 3
Activation and suppression have different spatial profiles.

(a) Lateral and axial spatial profile of activation (left) and suppression (right) relative to nearest target site co-ordinate: for each neuron plot its distance to nearest target site co-ordinate …

Behaviour follows the activity of targeted ensembles despite matched suppression in the local network.

(a–c) Psychometric curve fits relating behavioural detection to the number of targets activated (a), the proportion of the background network activated (b) and the proportion of the background …

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