Stimulus-specificity of surround-induced responses in primary visual cortex

Reviewer #1 (Public Review):

Summary:

The authors report a study on how stimulation of receptive-field surround of V1 and LGN neurons affects their firing rates. Specifically, they examine stimuli in which a grey patch covers the classical RF of the cell and a stimulus appears in the surround. Using a number of different stimulus paradigms they find a long latency response in V1 (but not the LGN) which does not depend strongly on the characteristics of the surround grating (drifting vs static, continuous vs discontinuous, predictable grating vs unpredictable pink noise). They find that population responses to simple achromatic stimuli have a different structure that does not distinguish so clearly between the grey patch and other conditions and the latency of the response was similar regardless of whether the center or surround was stimulated by the achromatic surface. Taken together they propose that the surround-response is related to the representation of the grey surface itself. They relate their findings to previous studies that have put forward the concept of an 'inverse RF' based on strong responses to small grey patches on a full-screen grating. They also discuss their results in the context of studies that suggest that surround responses are related to predictions of the RF content or figure-ground segregation.

Strengths:

I find the study to be an interesting extension of the work on surround stimulation and the addition of the LGN data is useful showing that the surround-induced responses are not present in the feed-forward path. The conclusions appear solid, being based on large numbers of neurons obtained through Neuropixels recordings. The use of many different stimulus combinations provides a rich view of the nature of the surround-induced responses.

Weaknesses:

The statistics are pooled across animals, which is less appropriate for hierarchical data. There is no histological confirmation of placement of the electrode in the LGN and there is no analysis of eye or face movements which may have contributed to the surround-induced responses. There are also some missing statistics and methods details which make interpretation more difficult.

Reviewer #2 (Public Review):

Cuevas et al. investigate the stimulus selectivity of surround-induced responses in the mouse primary visual cortex (V1). While classical experiments in non-human primates and cats have generally demonstrated that stimuli in the surround receptive field (RF) of V1 neurons only modulate activity to stimuli presented in the center RF, without eliciting responses when presented in isolation, recent studies in mouse V1 have indicated the presence of purely surround-induced responses. These have been linked to prediction error signals. In this study, the authors build on these previous findings by systematically examining the stimulus selectivity of surround-induced responses.

Using neuropixels recordings in V1 and the dorsal lateral geniculate nucleus (dLGN) of head-fixed, awake mice, the authors presented various stimulus types (gratings, noise, surfaces) to the center and surround, as well as to the surround only, while also varying the size of the stimuli. Their results confirm the existence of surround-induced responses in mouse V1 neurons, demonstrating that these responses do not require spatial or temporal coherence across the surround, as would be expected if they were linked to prediction error signals. Instead, they suggest that surround-induced responses primarily reflect the representation of the achromatic surface itself.

The literature on center-surround effects in V1 is extensive and sometimes confusing, likely due to the use of different species, stimulus configurations, contrast levels, and stimulus sizes across different studies. It is plausible that surround modulation serves multiple functions depending on these parameters. Within this context, the study by Cuevas et al. makes a significant contribution by exploring the relationship between surround-induced responses in mouse V1 and stimulus statistics. The research is meticulously conducted and incorporates a wide range of experimental stimulus conditions, providing valuable new insights regarding center-surround interactions.

However, the current manuscript presents challenges in readability for both non-experts and experts. Some conclusions are difficult to follow or not clearly justified.

I recommend the following improvements to enhance clarity and comprehension:

(1) Clearly state the hypotheses being tested at the beginning of the manuscript.

(2) Always specify the species used in referenced studies to avoid confusion (esp. Introduction and Discussion).

(3) Briefly summarize the main findings at the beginning of each section to provide context.

(4) Clearly define important terms such as "surface stimulus" and "early vs. late stimulus period" to ensure understanding.

(5) Provide a rationale for each result section, explaining the significance of the findings.

(6) Offer a detailed explanation of why the results do not support the prediction error signal hypothesis but instead suggest an encoding of the achromatic surface.

These adjustments will help make the manuscript more accessible and its conclusions more compelling.

Reviewer #3 (Public Review):

Summary:

This paper explores the phenomenon whereby some V1 neurons can respond to stimuli presented far outside their receptive field. It introduces three possible explanations for this phenomenon and it presents experiments that it argues favor the third explanation, based on figure/ground segregation.

Strengths:

I found it useful to see that there are three possible interpretations of this finding (prediction error, interpolation, and figure/ground). I also found it useful to see a comparison with LGN responses and to see that the effect there is not only absent but actually the opposite: stimuli presented far outside the receptive field suppress rather than drive the neurons. Other experiments presented here may also be of interest to the field.

Weaknesses:

The paper is not particularly clear. I came out of it rather confused as to which hypotheses were still standing and which hypotheses were ruled out. There are numerous ways to make it clearer.