Reconstruction of Sparse Circuits Using Multi-neuronal Excitation (RESCUME)

TL;DR

This paper introduces a compressive sensing-based method for efficiently reconstructing sparse neural circuits by stimulating multiple neurons simultaneously and recording post-synaptic responses, significantly reducing experimental time.

Contribution

The authors propose a novel multineuronal stimulation and decoding approach that improves efficiency in reconstructing neural connectivity compared to traditional methods.

Findings

Simulation results show significant time savings over brute force methods.

The approach is robust under realistic noise and non-linear conditions.

Parallel monitoring of multiple neurons enables comprehensive circuit mapping.

Abstract

One of the central problems in neuroscience is reconstructing synaptic connectivity in neural circuits. Synapses onto a neuron can be probed by sequentially stimulating potentially pre-synaptic neurons while monitoring the membrane voltage of the post-synaptic neuron. Reconstructing a large neural circuit using such a "brute force" approach is rather time-consuming and inefficient because the connectivity in neural circuits is sparse. Instead, we propose to measure a post-synaptic neuron's voltage while stimulating sequentially random subsets of multiple potentially pre-synaptic neurons. To reconstruct these synaptic connections from the recorded voltage we apply a decoding algorithm recently developed for compressive sensing. Compared to the brute force approach, our method promises significant time savings that grow with the size of the circuit. We use computer simulations to find optimal stimulation parameters and explore the feasibility of our reconstruction method under realistic experimental conditions including noise and non-linear synaptic integration. Multineuronal stimulation allows reconstructing synaptic connectivity just from the spiking activity of post-synaptic neurons, even when sub-threshold voltage is unavailable. By using calcium indicators, voltage-sensitive dyes, or multi-electrode arrays one could monitor activity of multiple postsynaptic neurons simultaneously, thus mapping their synaptic inputs in parallel, potentially reconstructing a complete neural circuit.