Methods to Construct Biological Neural Circuits

Recent biotechnological innovations make feasible the new paradigm of creating biological neural circuits de novo. With advances in protein, cell and tissue engineering techniques, as well as cellular reprogramming methods, we are entering an era where the construction of neural circuits can open completely new ways for studying nervous systems and for treating nervous system disorders. I explore here three technologies, namely cellular engraftment, neuronal reprogramming and transsynaptic molecule engineering, and delineate how they are being used in a variety of basic research and translational medicine contexts. In basic neuroscience, neural circuit construction methods are enabling ways to study causality in neural development (e.g. neural precursor differentiation and migration) and circuit function (e.g. excitation/inhibition balance, neural population dynamics). In translational neuroscience, they are providing opportunities for the targeted correction of circuit malfunction in brain disorders, both psychiatric (e.g. schizophrenia) and neurological (e.g. Parkinson’s, Huntington’s and Alzheimer’s disease, as well as epilepsy). I discuss the challenges that these methods currently face, such as targeting specificity and cell survival, and outline future paths and opportunities to realize the full potential of technologies for creating new biological neural circuits.