How can neurones be controlled with light?

What is optogenetics?

It is a technique that uses light-sensitive proteins called opsins to control the activity of selected neurones right “on time”. 

How are mammalian cells made light-sensitive? What steps does the process involve? 

Making mammalian cells light-sensitive involves introducing genetic instructions that let selected neurones produce opsins. One common way to deliver these instructions is by using specially engineered, non-disease-causing viral vectors that carry the genetic material into target cells. 

Once produced, opsins sit in the cell membrane and, when light shines, they open a small pore that lets specific ions cross the membrane. This movement modifies the electrical activity of the neurone, allowing researchers to activate or inactivate specific neurones on demand.

And where do the opsins used in optogenetics come from?

They come from different organisms, and scientists have adapted them to control cell activity with light.

The most commonly used are microbial opsins, which originate from microorganisms such as archaea, bacteria, and algae. These proteins naturally help organisms respond to light. Scientists have adapted them for optogenetics because some can directly control ion movement across a cell membrane when illuminated. Different opsins respond to different wavelengths of light, ranging from blue to red, allowing researchers to select the type of light that best suited their experiment. 

The opsins that have been recognised by the 2026 Nobel Prize are channelrhodopsins, found in an algae known as Chlamydomonas.

The second type of opsin is found in animals, typically in the photoreceptor cells of the retina. Unlike many microbial opsins, visual opsins activate a chain of biochemical reactions through G proteins when they absorb light. These reactions ultimately change the electrical activity of retinal cells, enabling the perception of light. 

What do you consider the most significant discovery or breakthrough made possible by optogenetics, and why?

It is difficult to choose just one achievement because optogenetics has opened new possibilities in neuroscience, vision restoration, and the study of other biological systems. However, I believe that one of the field’s most significant achievements is allowing scientists to investigate how specific groups of neurones contribute to behaviour and neurological disorders with remarkable precision.

This is particularly important when thinking about mental health conditions such as depression. Depression can profoundly affect a person’s ability to carry out everyday activities, maintain relationships, and function at work. Although effective treatments exist, some people do not respond well to current therapies. Optogenetics allows researchers to investigate the neural circuits involved in mood and behaviour, helping them better understand these complex conditions and explore potential future treatments.

Imagine being able to precisely influence the activity of a specific neural circuit involved in a depressive state, almost as if adjusting a switch. This is an exciting scientific possibility, but we are not yet able to switch on and off depressive episodes in humans. 

What future applications of optogenetics in medicine are you particularly looking forward to?

I am particularly excited about less invasive ways of controlling neuronal activity.

Currently, many optogenetic experiments rely on the implantation of tiny optical fibres to deliver light to target neurones. My research explores an alternative approach: developing light nanotransducers based on upconversion nanoparticles. These nanomaterials convert near-infrared light, which penetrates deeper and scatters less in biological tissue, to visible light that can activate opsins.

The idea is to use near-infrared light to excite nanoparticles near target cells, allowing them to emit the specific colour needed to activate opsins. In the long term, this approach could help reduce the need for implanted optical fibres in certain applications, although important technical challenges remain.

In our photonics laboratory at the AGH University of Krakow, we are working to improve the efficiency and reproducibility of these nanoparticles and ensure reliable optical properties. Next, we will coat them with biocompatible materials and evaluate their safety using cell-based experiments. We would then investigate whether the nanoparticles produce sufficient light to activate the selected opsins in cells.

This is a step-by-step process and considerable research remains before such an approach could be used in patients. Nevertheless, I find it exciting because it brings together materials science, photonics, and neuroscience to explore new ways of interacting with living cells using light. Ultimately, I hope this research contributes to less invasive approaches to neuronal modulation and, potentially, future medical applications.

What is the main objective of your NCN-funded project, “Glass@Nanocrystal Hybrid Core–Shell Platform for Simultaneous Imaging and Thermometry”?

The project aims to develop hybrid nanoplatforms that combine two complementary functions: imaging and microscopic temperature sensing. 

We are developing structures that combine a glass core with a crystalline nanocrystal shell and incorporate lanthanide ions with specific optical properties. The glass core supports imaging, while the crystalline shell enables optical temperature measurements by analysing nanoparticle-emitted light. 

By integrating both functions into a single platform, we aim to obtain spatial information while simultaneously measuring the local temperature. 

Why are high-resolution imaging and temperature measurement inside tissues important? What potential applications do these techniques have?

High-resolution imaging allows researchers to observe biological structures on a small scale, while temperature monitoring provides complementary information about the local physiological environment. Even small temperature variations may reflect changes in biological processes, such as inflammation or altered cellular metabolism, but these changes must be interpreted in their physiological context.

This is particularly relevant in cancer research, where the detection of early changes in small or developing lesions remains a major challenge. Conventional imaging techniques have different spatial resolutions and detection limits, and very small abnormalities (smaller than mm) may be difficult to identify depending on the method used. However, a 1 °C temperature change in physiological tissue can signal such disruptions. 

By combining high-resolution imaging with sensitive optical thermometry in a single nanoplatform, we aim to provide complementary information about tissue structure and local temperature. In the long term, this approach could support research into early disease detection and the monitoring of biological processes, potentially enabling more sensitive diagnostic tools.

Could this project contribute to the development of optogenetics? If so, in what way?

Yes. It could lead to the development of new ways to deliver light to opsins.

Lanthanide-based nanomaterials are particularly interesting because they can emit light at different wavelengths. For example, upconversion nanoparticles can convert near-infrared light into visible light, potentially activating nearby opsins. This could offer an alternative to implanted optical fibres for delivering light directly to target cells.

Our project focuses on developing hybrid nanoplatforms for imaging and optical temperature sensing, but the optical properties of these materials could also be employed as light nanotransducers. At the same time, researchers are developing and investigating opsins that respond to longer wavelengths, including red light. If researchers can combine suitable opsins with efficient nanotransducers, they may be able to explore alternative approaches to light delivery, including systems based on NIR-to-NIR conversion.

Did the experience you gained during the workshop with Professor Deisseroth or the discussions held there influence the direction of research at AGH University in any way?

Definitely. The workshop in Professor Karl Deisseroth’s laboratory at Stanford University significantly influenced how I approach my research at AGH University.

During the workshop, I gained hands-on experience with opsin injection and optical fibre implantation, and I observed how light stimulation can trigger a specific response in a living animal. This experience helped me better understand the practical aspects of optogenetics beyond what scientific publications alone can teach.

It also made me reconsider the challenges involved in developing light nanotransducers. When reading about the optical power required to activate opsins, it can be difficult to fully appreciate the practical implications. Observing the experiments firsthand helped me recognise how important it is to develop nanomaterials with sufficient emission efficiency to produce the desired biological response. I also gained a better understanding of the importance of stimulation parameters, including wavelength, light intensity, pulse duration, and frequency.

Furthermore, discussions with Professor Deisseroth provided valuable guidance on selecting suitable opsins for our research. This helped us better consider the compatibility between the light emission of our nanomaterials and the light sensitivity of the proteins we aim to activate.

What do you consider to be the most significant achievement of the AGH University team in the field of optogenetics?

I think it is important to distinguish between the achievements of the international optogenetics community and the contributions that our team at AGH University is working toward.

Some of the most exciting advances worldwide include the use of optogenetics to restore limited visual responses in people with certain forms of retinal degeneration. Researchers are also exploring light-based approaches to improve the precision of cochlear stimulation, with the aim of providing more selective auditory stimulation in the future.

At AGH University, our research focuses on the materials science challenges that could help advance optogenetics. We are exploring how lanthanide-based nanomaterials can be developed as light nanotransducers, potentially offering alternative ways to deliver the wavelengths needed to activate opsins. This is an important step toward investigating whether optical stimulation could become less invasive and more practical in certain biological applications.

Looking ahead, I believe one of the most remarkable achievements would be developing approaches that not only manage symptoms but eventually restore lost biological functions. This is particularly relevant for neurological disorders that affect movement, memory, or mood. Although much more research is needed before such applications become clinical realities, optogenetics offers a powerful way to investigate how specific neural circuits contribute to these functions.

What are your research goals and what are you going to work on in the near future?

I would like to focus on functionalising our photoluminescent nanoparticles with different biocompatible polymers to improve their stability and compatibility with biological environments. We will then evaluate their potential cytotoxic effects using different cell lines to assess their suitability for biological applications.

After characterising their biocompatibility, we will introduce suggested opsins into cultured cells and test whether our nanoparticles emit enough light to trigger the desired cellular response.

Which of your research projects are you most proud of? Could you explain what it entails to a layperson?

It must be the research I conducted on the stimulation of hippocampal neurones using magnetic hyperthermia during my first postdoctoral work. This project was particularly meaningful to me because I was involved in the entire process, from developing the magnetic nanoparticles to learning to extract and culture neurones and investigate their responses to magnetic stimulation. I could compare the cells’ responses with and without stimulation and observe how the materials we developed influenced a living biological system.

For me, seeing this interaction was fascinating. We often think of nanomaterials as extremely small structures with specific physical or chemical properties, but this project showed me how these properties can be used to influence biological processes.

The experience also made me think about the limitations of the technique, particularly the challenge of controlling temperature and avoiding excessive heating that could damage cells. Since my background is in photoluminescent materials, I began exploring how light-emitting nanoparticles could help us monitor temperature at a microscopic scale. My long-term ambition is to combine temperature nanosensors with magnetic nanoparticles to better understand and monitor the heat generated during magnetic stimulation, potentially helping researchers control it more precisely.

This project helped shape my current research interests by showing me how materials science, photonics, and neuroscience can come together to address biological challenges.