Live-cell Analysis for Neuroscientists

The last few decades have witnessed a remarkable development in the field of neuroscience. For example, in-depth sequencing and epidemiological work have produced startling discoveries about the genetic basis of neurological diseases. High-resolution techniques also resolved several learning and memory signaling pathways, both at the cellular and molecular level. However, identifying truly effective new treatments for patients appears to be a challenge, and most of the functions of the human brain and nervous system remain a mystery.

There are several fundamental challenges. First, the nervous system is extremely complex: there are >100 billion interconnected neurons in the average human brain and many other supporting cells. These cells are highly plastic and are constantly changing with development, maturity, and the almost inevitable decline of age and disease. Second, it is extremely difficult to access ethically healthy and diseased human neural tissue for ethical consensus research. Small biopsy samples can be obtained but are rarely sufficient for in-depth in vitro analyzes and functional studies. Of all cells, neurons are extremely sensitive to damage or environmental changes (eg hypoxia), adding even more technical complexity. Ultimately, animal models have yielded questionable translation values ​​in many cases, especially for psychiatric and neurodegenerative disorders, highlighting only the obvious differences between lower and higher-order species.

Recent advances in stem cell technologies provide an exciting alternative pathway where researchers can use human-induced pluripotent stem cells (iPSCs) to create differentiated neurons and supporting cells (eg, astrocytes, microglia). Although this approach is still in its infancy, the potential exists to build fully humanized and patient-specific advanced cellular models for neuroscience. To fulfill this promise, much work is needed to optimize reprogramming and differentiation methods and to construct and validate cellular biological assays representative of native (pathogenic) human physiology. Phenotypic measurements reporting long-term functional results and plastic changes will be very helpful in this regard.

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