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Behavioral state-dependent effects of electrical stimulation on neuronal activity

Periodic Reporting for period 1 - ELECTRONEUROSTIM (Behavioral state-dependent effects of electrical stimulation on neuronal activity)

Periodo di rendicontazione: 2023-01-01 al 2024-12-31

Electrical brain stimulation is a technique with a large potential to study brain activity and treat a variety of pathological conditions. Despite its wide use, many open questions remain about the underlying mechanisms. For instance, it is not fully clear how electrical stimulation affects the activity of neuronal populations in-vivo and whether behavioral states modulate such effects. Here we aimed to fill this knowledge gap developing and using cutting edge tools to stimulate the mouse brain as well as state-of-the-art imaging techniques to monitor neuronal activity and gain a deep understanding on how electricity alters brain function. Furthermore, computational models were developed to understand the basic mechanisms of interaction between electricity and neurons. Insights from this work will likely shed light on the realm of possible effects of electrical stimulation, and on how brain activity could be shaped to achieve specific behavioral outcomes. Ultimately, this knowledge may lead to the rational design of stimulation protocols that could be applied in humans, ideally non-invasively, to restore brain functions.
1) I designed, developed and tested electrodes made of conductive polymers. These electrodes are extremely thin and transparent and therefore compatible with imaging techniques.

2) I tested the electrodes in-vivo in anesthetized mice and quantified the electric field that is generated inside the brain combining the experimental data with a finite-element model of stimulation that I developed. I showed that these electrodes can be used to generate electric fields whose values cover a large range of the electric fields that are generated in human applications.

3) I developed a pipeline to simulate the effects of low-amplitude electrical stimulation on realistic neuron models of various neuron types. I found that the effects of the stimulation on neuronal activity largely varies across and within distinct neuron types.
My early results show that the electrodes made of conductive polymers are highly suited to study the effects of electrical stimulation on neuronal activity. In particular they have appropriate charge capabilities and their transparency make them compatible with imaging techniques. The inkjet printing procedure is relatively inexpensive and therefore this type of electrodes have potential to become a new tool to modulate and study brain function.
The computational modeling work goes beyond state-of-the-art because it incorporates data from datasets comprising hundreds of neurons and therefore has the potential to provide direct insights on how electrical stimulation affects different neuron types as well as inform future models of electrical stimulation.