All-optical dynamic clamp system
This project is supported by NeurotechEU fellowship.
Question:
If neurons, that are not connected in real-life, are made to be connected, how does it influence the network dynamics?​
I started a project to develop an "all-optical dynamic clamp" system as a tool that will ultimately allow us to address the question above.​ Once successful, an experimenter will be able to select neurons under a microscope to connect by artificial synapses in an "all-optical" setting (Figure left below).
It will allows us, for example, to make synaptic connections between cultured neurons derived from human iPSCs of healthy and diseased to investigate potential approaches to rescue pathological neural activities. (Figure right above)
What is an "all-optical" setting and what is an "all-optical dynamic clamp? As shown below left, in the all-optical setting, the conventional electric recording and stimulation techniques are replaced by optical recording and stimulation techniques. By implementing the dynamic clamp system to it, a closed-loop system can be made: (artificial) synaptic connections between neurons can be made just as in the conventional electrical dynamic clamp system but in an all-optical setting as shown below right. With the rapid progresses in bioengineering to develop design molecules for optical recording and stimulations, optics applied to neuroscience, and computer technologies, it will be possible in the future to deal with a population of neurons at once.
Ultimately, the system configuration will look like the one shown below left with the voltage indicator (Archon1) and the optogenetic agent (ChETA) inserted to target neurons, and the optical neural activities are captured by Micromanager (MM). The signals from MM are pipelined to the dynamic clamp (DC) system where neural stimulation are made. The synaptic output of DC is given to a light source to illuminate the neurons carrying ChETA with the time course of the synaptic event.
In collaboration with Imran Avci's laboratory at Vrij Universiteit Amsterdam (Imran Avci and Hamed Nikbakht), Thomas Nowotny (University of Sussex), Felix Kern (University of Tokyo), my intern student, Bas Drost, and I have been working on the system and we made significant progress in the last half year. The closed loop is now complete.
With the configuration shown below left, the results are demonstrated. For the demonstration purpose, a piece of tissue paper is placed in the recording champer under a microscope. As shown on the right, by mimicking action potentials with a brief LED illumination, the signals are captured by MM, which are passed on to DC where an optical synapse 1 is connected to a model neuron (Hodgkin & Huxley model, HH), which fires action potentials in response, that triggered optical synapse 2 that drove the LED signals that are. captured byMM again.
movie clips for the demonstration
monosynaptic configuration
dysynaptic configuration (subthreshold)
dysynaptic configuration (suprathreshold)