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‎README.md‎

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[![Ruff](https://img.shields.io/endpoint?url=https://raw.githubusercontent.com/astral-sh/ruff/main/assets/badge/v2.json)](https://github.com/astral-sh/ruff)
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[![DOI](https://zenodo.org/badge/262130097.svg)](https://zenodo.org/doi/10.5281/zenodo.7036270)
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<h1>
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<p align="center">
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<img
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style="display: block;
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<img
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style="display: block;
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width: 50%;"
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src="https://user-images.githubusercontent.com/19983357/187561700-100b853a-d226-4039-a580-1d798b00f9e4.png"
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src="https://user-images.githubusercontent.com/19983357/187561700-100b853a-d226-4039-a580-1d798b00f9e4.png"
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alt="Cleo: the Closed-Loop, Electrophysiology, and Optophysiology experiment simulation testbed">
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</img>
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</p>
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</h1>
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Hello there!
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Cleo has the goal of bridging theory and experiment for mesoscale neuroscience, facilitating electrode recording, optogenetic stimulation, and closed-loop experiments (e.g., real-time input and output processing) with the [Brian 2](https://brian2.readthedocs.io/en/stable/) spiking neural network simulator.
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We hope users will find these components useful for prototyping experiments, innovating methods, and testing observations about a hypotheses *in silico*, incorporating into spiking neural network models laboratory techniques ranging from passive observation to complex model-based feedback control.
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Cleo also serves as an extensible, modular base for developing additional recording and stimulation modules for Brian simulations.
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This package was developed by [Kyle Johnsen](https://kjohnsen.org) and Nathan Cruzado under the direction of [Chris Rozell](https://siplab.gatech.edu) at Georgia Institute of Technology.
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See the preprint [here](https://www.biorxiv.org/content/10.1101/2023.01.27.525963).
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See the publication [here](https://www.jneurosci.org/content/46/1/e2239242025).
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<p align="center">
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<img
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style="display: block;
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<img
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width: 90%;"
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src="https://raw.githubusercontent.com/siplab-gt/cleo/master/docs/_static/cleo-overview-table.png"
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src="https://raw.githubusercontent.com/siplab-gt/cleo/master/docs/_static/cleo-overview-table.png"
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alt="Overview table of Cleo's closed-loop control, ephys, and ophys features">
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</img>
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</p>
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## <img align="bottom" src="https://user-images.githubusercontent.com/19983357/167456512-fb10619b-255e-4a53-8ed9-79ae954d3ff4.png" alt="🖥️" > Closed Loop processing
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Cleo allows for flexible I/O processing in real time, enabling the simulation of closed-loop experiments such as event-triggered or feedback control.
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The user can also add latency to the stimulation to study the effects of computation delays.
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## <img align="bottom" src="https://user-images.githubusercontent.com/19983357/167461111-b0a3746c-03fa-47b7-a9a9-7b651157044f.png" alt="🔌" > Electrode recording
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Cleo provides functions for configuring electrode arrays and placing them in arbitrary locations in the simulation.
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The user can then specify parameters for probabilistic spike detection or a spike-based LFP approximation developed by [Teleńczuk et al., 2020](https://www.sciencedirect.com/science/article/pii/S0165027020302946).
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## <img align="bottom" src="https://user-images.githubusercontent.com/19983357/187728089-62fae854-1d69-4e8f-a597-a25934ca3eaa.png" alt="⚡" > 1P/2P optogenetic stimulation
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By modeling light propagation and opsins, Cleo enables users to flexibly add photostimulation to their model.
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Both a four-state Markov state model of opsin kinetics is available, as well as a minimal proportional current option for compatibility with simple neuron models.
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Cleo also accounts for opsin action spectra to model the effects of multi-light/wavelength/opsin crosstalk and heterogeneous expression.
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The calcium indicator model of [Song et al., 2021](https://www.sciencedirect.com/science/article/pii/S0165027021001084) is implemented, with parameters included for GCaMP6 variants.
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## 🚀 Getting started
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Just use pip to install&mdash;the name on PyPI is `cleosim`:
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```bash
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pip install cleosim
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```
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Then head to the [overview section of the documentation](https://cleosim.readthedocs.io/latest/overview.html) for a more detailed discussion of motivation, structure, and basic usage.
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## 📚 Related resources
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Those using Cleo to simulate closed-loop control experiments may be interested in software developed for the execution of real-time, *in-vivo* experiments.
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Developed by members of [Chris Rozell](https://siplab.gatech.edu)'s and [Garrett Stanley](https://stanley.gatech.edu/)'s labs at Georgia Tech, the [CLOCTools repository](https://cloctools.github.io) can serve these users in two ways:
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The `ldsCtrlEst` library implements adaptive linear dynamical system-based control while the `hmm` library can generate and decode systems with discrete latent states and observations.
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<p align="center">
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<img
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style="display: block;
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<img
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width: 100%;"
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src="https://raw.githubusercontent.com/siplab-gt/cleo/master/docs/_static/cloctools_and_cleo.png"
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src="https://raw.githubusercontent.com/siplab-gt/cleo/master/docs/_static/cloctools_and_cleo.png"
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alt="CLOCTools and Cleo">
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</img>
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</p>
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### 📃 Publications
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[**Cleo: A testbed for bridging model and experiment by simulating closed-loop stimulation, electrode recording, and optophysiology**](https://www.biorxiv.org/content/10.1101/2023.01.27.525963)<br>
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K.A. Johnsen, N.A. Cruzado, Z.C. Menard, A.A. Willats, A.S. Charles, and C.J. Rozell. *bioRxiv*, 2023.
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[**CLOC Tools: A Library of Tools for Closed-Loop Neuroscience**](https://github.com/cloctools/tools-for-neuro-control-manuscript)<br>
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[**Bridging Model and Experiment in Systems Neuroscience with Cleo: The Closed-Loop, Electrophysiology, and Optophysiology Simulation Testbed**](https://www.jneurosci.org/content/46/1/e2239242025)<br>
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K.A. Johnsen, N.A. Cruzado, Z.C. Menard, A.A. Willats, A.S. Charles, J.E. Markowitz, and C.J. Rozell. *Journal of Neuroscience*, 2026.
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<!-- THESE AREN'T PUBLICLY VIEWABLE -->
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<!-- [**CLOC Tools: A Library of Tools for Closed-Loop Neuroscience**](https://github.com/cloctools/tools-for-neuro-control-manuscript)<br>
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A.A. Willats, M.F. Bolus, K.A. Johnsen, G.B. Stanley, and C.J. Rozell. *In prep*, 2023.
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[**State-Aware Control of Switching Neural Dynamics**](https://github.com/awillats/state-aware-control)<br>
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A.A. Willats, M.F. Bolus, C.J. Whitmire, G.B. Stanley, and C.J. Rozell. *In prep*, 2023.
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A.A. Willats, M.F. Bolus, C.J. Whitmire, G.B. Stanley, and C.J. Rozell. *In prep*, 2023. -->
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[**Closed-Loop Identifiability in Neural Circuits**](https://github.com/awillats/clinc)<br>
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A. Willats, M. O'Shaughnessy, and C. Rozell. *In prep*, 2023.

‎docs/showcase.md‎

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Here you can find links to code where Cleo has been used in research.
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- Cleo [preprint](https://www.biorxiv.org/content/10.1101/2023.01.27.525963)
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- [Seizure recording and SWR evocation experiments in a hippocampus model](https://github.com/siplab-gt/cleo-hpc-experiments)
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- [Bidirectional in-vitro "optoclamp" of firing rate](https://github.com/siplab-gt/cleo/blob/master/notebooks/newman15_validation.ipynb)
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- [All-optical control of individual neurons with off-target effects](https://github.com/siplab-gt/cleo/blob/master/notebooks/all_optical_fig.ipynb)
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- [Closed-loop rejection of a traveling wave in rodent S1](https://github.com/siplab-gt/cleo-traveling-wave-rejection)
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- [Firing rate clamp to disrupt mouse V1 plasticity](https://github.com/siplab-gt/cleo-v1-plasticity-expt)
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- Cleo [publication](https://www.jneurosci.org/content/46/1/e2239242025)
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- [Seizure recording and SWR evocation experiments in a hippocampus model](https://github.com/siplab-gt/cleo-hpc-experiments)
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- [Bidirectional in-vitro "optoclamp" of firing rate](https://github.com/siplab-gt/cleo/blob/master/notebooks/newman15_validation.ipynb)
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- [All-optical control of individual neurons with off-target effects](https://github.com/siplab-gt/cleo/blob/master/notebooks/all_optical_fig.ipynb)
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- [Closed-loop rejection of a traveling wave in rodent S1](https://github.com/siplab-gt/cleo-traveling-wave-rejection)
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- [Firing rate clamp to disrupt mouse V1 plasticity](https://github.com/siplab-gt/cleo-v1-plasticity-expt)

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