Nonlinear Photonics for Neuroscience

Exploring the Brain with Light: The NPN Group at IBEC

The Nonlinear Photonics for Neuroscience (NPN) group at IBEC is dedicated to advancing our understanding of the brain through the development of cutting-edge microscopy techniques. Our work is guided by the belief that breakthroughs in neuroscience often stem from technological innovations, with photonic tools playing a leading role.

At the intersection of physics, engineering, and neuroscience, our research focuses on three core objectives:

1. Leveraging Nonlinear Optical Phenomena: We study effects like two-photon excited fluorescence and second harmonic generation and enhance them by precisely shaping ultrafast laser beams in both space and time.
   
2. Pioneering New Microscopy Techniques: Building on our optical expertise, we develop innovative imaging and photostimulation tools that could provide deeper insights into the role of neuronal circuits. 
   
3. Applications in Neuroscience: We partner with leading neuroscientists to apply our technologies to the study of neuronal circuits in small animal models, aiming to help deciphering brain functions.                                                                                                                                                                                                                                           
   
            

Shining Light on the Brain’s Mysteries

Neuronal circuits are the brain’s fundamental units, responsible for processing information from the world around us. They shape our perceptions, guide our actions, and define our identities. Understanding how neuronal circuits work is one of the greatest scientific challenges of our time, which requires extremely sophisticated tools to probe them.

In the past 15 years, the field of neurophotonics has revolutionized neuroscience by enabling us to visualize and manipulate brain activity with light. Fluorescent indicators allow us to see neurons “fire”, while optogenetic techniques give us the power to control neural activity using light. However, the ability to truly decipher the brain’s complex networks depends on the continued development of powerful microscopy techniques.

At the NPN group, we design build and apply state-of-the-art microscopy tools for neuroscience. Our mission is to provide the scientific community with the technologies needed to illuminate the brain’s mysteries.

Current Research directions

1. Spatial and Temporal Shaping of Ultrafast Lasers with Diffractive Optical Elements

A central aspect of our research is the precise shaping of laser beams in both space and time. For spatial shaping, we utilize spatial light modulators (SLMs) to dynamically adjust the distribution of excitation at the sample plane, allowing us to target specific cells more accurately (Ref. Accanto*, Molinier* et al., Optica, 2018). Temporal shaping is essential for optimizing nonlinear excitation and can be achieved actively, using pulse shapers based on SLMs (Accanto et al. Light: Science and Applications, 2014), or passively, by incorporating elements that introduce spatially varying delays to the laser beam (Ref. Lorca-Cámara et al., Biomedical Optics Express).

2. Miniaturized Two-Photon Fiberscope for Studying the Brain in Freely Moving Animals

To study animals engaged in natural behaviors, the field of neurophotonics has seen a surge in the development of portable two-photon (2P) microscopes, enabling the imaging of neuronal activity in freely moving mice. Our group has been at the forefront of this “miniaturized microscope revolution,” demonstrating the first flexible 2P fiberscope for optogenetic photostimulation (2P-FENDO, Ref. Accanto*, Blot*, Lorca-Cámara* et al., Neuron). We are currently focused on enhancing this technology’s capabilities and have several open positions for postdocs and PhD students.

3. Large Field-of-View Two-Photon Microscopy Using Off-the-Shelf Components

To understand how neuronal circuits process information, it’s crucial to simultaneously examine spatially separated but connected brain regions while maintaining single-neuron resolution—a major challenge in microscopy. Our recent research efforts aim to expand the accessible field of view of two-photon microscopes through simple and easily shareable solutions that can benefit the wider neuroscience community. We also have openings for postdoctoral researchers and PhD students in this area.

Equipment used

• Ultrafast infrared lases: The heartbeat of our experiments, these state-of-the-art lasers generate intense pulses for high-resolution imaging and photostimulation. Our team customizes optical setups to direct each pulse precisely in space and time, driving innovative research in microscopy and neurobiology.
• Spatial light modulators: These modulators enable us to fine-tune laser beams, guiding them to precise spatial locations or altering their temporal profiles. They are essential tools for customizing light to meet our experimental needs.
• Microscopes: We develop novel microscopy techniques to make brain study more accessible, versatile, and precise. Our goal is to provide the tools that help unravel the mysteries of the brain from every possible angle.

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