Most discriminative stimuli for functional cell type clustering
Max F. Burg, Thomas Zenkel, Michaela Vystr\v{c}ilov\'a, Jonathan, Oesterle, Larissa H\"ofling, Konstantin F. Willeke, Jan Lause, Sarah, M\"uller, Paul G. Fahey, Zhiwei Ding, Kelli Restivo, Shashwat Sridhar, Tim, Gollisch, Philipp Berens, Andreas S. Tolias, Thomas Euler

TL;DR
This paper introduces an optimization-based clustering method using deep predictive models to identify functional neuron types through Most Discriminative Stimuli, enabling fast, unbiased, and interpretable classification across species and brain regions.
Contribution
It presents a novel approach combining stimulus optimization and clustering to discover functional neuron types without prior biases or extensive training.
Findings
Successfully recovers functional clusters in multiple species and brain areas.
Generates interpretable stimuli that distinguish neuron types.
Operates efficiently without large natural scene datasets.
Abstract
Identifying cell types and understanding their functional properties is crucial for unraveling the mechanisms underlying perception and cognition. In the retina, functional types can be identified by carefully selected stimuli, but this requires expert domain knowledge and biases the procedure towards previously known cell types. In the visual cortex, it is still unknown what functional types exist and how to identify them. Thus, for unbiased identification of the functional cell types in retina and visual cortex, new approaches are needed. Here we propose an optimization-based clustering approach using deep predictive models to obtain functional clusters of neurons using Most Discriminative Stimuli (MDS). Our approach alternates between stimulus optimization with cluster reassignment akin to an expectation-maximization algorithm. The algorithm recovers functional clusters in mouse…
Peer Reviews
Decision·ICLR 2024 poster
The paper is relatively easy to follow and well-structured. The method seems to be straightforward and intuitive. The authors provided multiple experiments to demonstrate the performance of the proposed framework.
My primary concern is how useful and interpretable the method will be for actual practice. The experiments essentially treated a carefully-examined existing publication as the ground truth to compare with. I assume in a lot of real scenarios, we might already have this kind of biological baselines. For cases where they are not available, the interpretability of the identified MDS might be important.
* MDS provides a time-efficient on-the-fly cell type assignment by using a concise stimulus. * MDS outperforms conventional approaches in identifying the correct cell type cluster, saving 20% of experimental time compared to traditional methods.
A potential weakness in the presented approach is that it assumes that the most informative stimuli for classifying cell types can be automatically chosen without requiring domain knowledge or expert input. While this is presented as an advantage, it may also be a limitation, as there could be cases where domain-specific insights are necessary for more accurate and nuanced cell type classification. Additionally, the success of the approach relies on the availability of a "digital twin" dataset,
Novelty and Importance: 1. The paper focus on a novel and important concept that finding inputs that maximize the difference of different functional cell types, which extend from single neuron MEI to group level. Evaluations: 1. The work has been comprehensively evaluated on multiple experiments across multiple animals to demonstrate the soundness of the proposed approach. Sensitivity analysis including different initialization, number of clusters are included. Writing: 1. The paper is well o
Method: 1. The clustering approach is based on the discreteness hypothesis of functional cell types, while ignoring the neurons might be close to the boundary or shows patterns that belongs to two functional cell types in different trials. Therefore, there might be limitation of separability. 2. It remains unclear how does the choice of neural networks or back-propagation algorithms affect the solutions. 3. Qualitatively, it is difficult to compare and interpret different MDS, and understand ho
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Taxonomy
TopicsNeural dynamics and brain function · Retinal Development and Disorders · Visual perception and processing mechanisms
