Optogenetics in the Era of Cerebral Organoids

Optogenetics refers to a combination of optical and genetic tools to control the activity of individual neurons and decode brain circuitry. Cerebral organoids derived from human pluripotent stem cells provide new opportunities for studying neurodevelopmental and neurodegenerative diseases in human-like tissue. The optogenetic technique and cerebral organoids can be combined to advance knowledge of the human brain and its related disorders and lead to more effective therapeutic approaches. The human brain has been deemed the most complex organ and has captivated neuroscientists for decades. Most studies of this organ have relied on reductionist model systems. Although all model systems are essentially wrong, cerebral organoids so far represent the closest recapitulation of human brain development and disease both in terms of cell diversity and organization. The optogenetic technique can be used in this context to study the functional neuroanatomy of the brain, to examine the neural circuits, and to determine the etiology of neurological disorders. In this opinion article, we suggest ways in which optogenetics can be combined with cerebral organoids to allow unprecedented precision and accuracy in studying normal and aberrant neurodevelopmental processes and, as well, neurodegenerative diseases. The human brain has been deemed the most complex organ and has captivated neuroscientists for decades. Most studies of this organ have relied on reductionist model systems. Although all model systems are essentially wrong, cerebral organoids so far represent the closest recapitulation of human brain development and disease both in terms of cell diversity and organization. The optogenetic technique can be used in this context to study the functional neuroanatomy of the brain, to examine the neural circuits, and to determine the etiology of neurological disorders. In this opinion article, we suggest ways in which optogenetics can be combined with cerebral organoids to allow unprecedented precision and accuracy in studying normal and aberrant neurodevelopmental processes and, as well, neurodegenerative diseases. a type of motor neuron disease. isoform of the APOE lipoprotein that is neutral with regards to Aβ accumulation in the brain. isoform of the APOE lipoprotein that is associated with increased Aβ accumulation in the brain. fusion of two or more region-specific organoids. a protein used by bacteria to pump protons out of the cell upon absorption of green light. a wide and thick nerve tract connecting the right and left hemisphere. a centrosomal protein involved in proper cell division. a protein used by algae to transport cations across the cell membrane upon absorption of blue light. cells in the ventricles of the brain that produce cerebrospinal fluid. a wide and thick nerve tract connecting the right and left hemisphere. a nerve tract that connects the midbrain to the spinal cord. the process by which the cerebral cortex is formed. an enzyme that catalyzes site-specific recombination between two DNA recognition sites. the dorsal portion of the forebrain consisting of the cerebrum. a technique in which an electric field is applied to increase cell permeability. a gradual process by which a normal brain becomes epileptic. the study of causes behind a disease. changes in the membrane potential that make the postsynaptic cell more likely to fire an action potential. encodes a basic fibroblast growth factor. encodes a transcription factor that acts as a transcriptional repressor. the main inhibitory neurotransmitter in the mature mammalian nervous system. a synapse that uses GABA as its neurotransmitter. a synapse that uses glutamate as its neurotransmitter. a protein used by bacteria to pump chloride into the cell upon absorption of yellow light. pluripotent stem cells derived from the human embryo. pluripotent stem cells generated from adult cells. a muscle spasm. a process by which the brain generates a seizure. isogenic cell lines have been genetically engineered from a parental cell line and only differ in the gene of interest. a disorder where parts or all of the brain appear smooth. encodes a cytoplasmic enzyme known as dardarin, variants of which are associated with an increased risk for Parkinson’s disease. encodes a neuron-specific RNA binding protein. a group of light-sensitive proteins that mediate ion flow across the cell membrane. a biological technique that uses light to control cells in living tissue. in vitro 3D structures that display important aspects of the anatomy and physiology of their in vivo counterparts and that develop from pluripotent or organ-specific stem cells through a self-organization process. entorhinal cortex input to the hippocampus. the largest neurogenic zone in the brain. in vitro 3D cell aggregates containing homogenous or heterogenous cells without self-organization. a protrusion on a dendrite that receives synaptic input from other cells. encodes a protein that is important in oxidative phosphorylation. fibers connecting the thalamus and cerebral cortex. electrical activity that is perceived as oscillations with a frequency of 4–8 Hz. the arrangement of parts or features of an organ. encodes a DNA exonuclease. a transient embryonic layer of tissue that that contains stem cells. a tissue graft from a donor of a different species.