Discussion: meetings/2025-09-09

[jeromelecoq]

Where to discuss the presentation from Sophie and Maxwell.

[jeromelecoq]

I thought it would be helpful to explain in more depth why I think this stimulus could be valuable to our work. I think there were a few questions from Sophie today. Perhaps I should have better explained this at the onset.

Our goal with this predictive processing study is to measure how neurons are making predictions across different contexts. In particular, we postulate that when sensory context is changed, the mechanisms leveraged by individual neurons to make predictions of future stimuli fundamentally changes. Our review of the literature has highlighted disagreement across studies in how inhibitory neurons or different neuronal pathways are recruited (among others mechanisms).

Fundamentally, we think it is due to difference in stimuli design. It is unfortunate but predictive processing has been tested with so many different tweaks in the stimuli that it is difficult to reconcile those difference to build proper models. We think the cortex has many tools in its toolkit to make predictions: Sensory-motor stimuli are leveraging input from motor cortex coming in superficial layers while quick repeats of a grating can trigger prediction solely based on local recurrent information, perhaps even at the level of single cells, within dendrites.

We aim to help consolidate the difference in the literature by collecting a dataset that span 4 different sensory context in the same mouse. and 3 recording modalities (2p, Neuropixels and Slap2) across different mice.

Our design leverages drifting grating heavily so it is important to this work that we have good baseline system identification (as Kaspar mentioned) across those stimuli. We see the visual cortex as leveraging those baseline system responses to make predictions. So much is known about neurons in the visual system in the mice: It is important we know which neurons have the same receptive fields.

Receptive fields also are a key QC metrics to know our recordings are working well, so we typically have a 10min Gabor receptive field block added to all of our sessions. It would be sad to do so much work to later realize that the neurons we are recording are not receiving inputs from our stimulus screen.

This is where our interest in your stimuli came about : Quick baseline system identification. In the rest of our sessions, we present repeated stimuli that pushes the system to adapt and learn using those baseline responses.

[jeromelecoq]

Does the rig geometry come into play in your generation? All of our stimuli are warped to flatten spatial frequencies. So I assume we need to adjust based on the distance to the eye and band of spatial frequencies presented ?

[mwshinn]

We aren't currently adjusting for this, but the zebra noise video could be adjusted after it is generated. Since the analysis is performed on the raw frames of the video, perhaps this would mean adjusting the video that is displayed but not the one that is analysed with the neural data. (@skriabineSop thoughts?)

[jeromelecoq]

1/ our warping is applied by bonsai after so it does not need to be in video generation
2/ How does the distance to screen influence the zebra movie you play?

[mwshinn]

Current parameters were tuned for rigs that have a 10 cm distance to the screen.

[skriabineSop]

So basically the only thing that the distance to screen distance would influence is the number of pixel on screen corresponding to a visual degree. And how many degrees of the visual field your screen covers. If you have a picture of your setup to share with us it would maybe help giving you advice on which parameters to use?

[Sarruedi]

I think there may have been some confusion about the potential reason for using the zebra noise stimulus. My view is that it could provide a very efficient way to parameterize the large stimulus space quickly. Our actual paradigm would then still make use of a much narrower stimulus set, based on drifting gratings at particular orientations as planned.

Personally, I like the idea of the zebra stimulus as a way to access neurons that may have different tuning preferences than those we typically capture with the standard RF mapping protocols. This would allow us to test whether the properties of cells we typically would not even register also change as a function of the experience we subject the animals to. It could be especially useful to use the zebra stimulus for a broad characterization at the very beginning of an experiment, and potentially again at the end of the session, as we have done in the SLAP2 design.

[Sarruedi]

I think it’s a very good approach. Checking early and late repeats is a clever way to build confidence in the stability of the units. We just may have to be careful in interpreting it under the Openscope paradigms, where tuning itself may potentially shift as a function of experiencing a bias in the presented stimuli

[maierav]

The spike sorting /stability concern is a good point.

Would it be possible to release the full bandwidth data for the Neuropixels?

There are still improvements on KiloSort popping up, and I would be happy to give them a try:
https://pubmed.ncbi.nlm.nih.gov/40791465/

This may also allow us to experiment with PhysMap/WaveMap:
https://pubmed.ncbi.nlm.nih.gov/37220000/
https://pubmed.ncbi.nlm.nih.gov/40766549/

[jeromelecoq]

After sleeping on it, one thing comes to mind is related to one point that @maierav raised. The current implementation of Zebra has the contrast to a maximum value. It is mostly black and white. When you change the contrast, it has been shown that different inhibitory populations kicks in. See: https://elifesciences.org/articles/55130
So I would think it could make sense to iterate Zebra to remove the binary aspect and construct zebra with varying contrast bases. The stimulus might need to be longer but it will allow to recruit across a wider range of cell classes.

[jeromelecoq]

That being said, It is possible that the responses are so reliable "because" the contrast is so high.

[jeromelecoq]

But that comes at the cost of NO activation of some inhibitory sub-populations.

[severine2305]

Hi @skriabineSop, great talk yesterday! Tell me if I missed it but did you ever compared directly the tuning properties of each cell obtained with the zebra stimulus vs the properties you obtain with drifting gratings and sparse noise? thank you.