Derek van der Kooy (born 1952), Fellow of Royal Society of Canada, is professor in the department of medical genetics and microbiology at the University of Toronto. He received a master's degree in psychology at the University of British Columbia and a Ph.D. in anatomy from Erasmus University in 1978, as well as in the department of anatomy at the University of Toronto in 1980. Van der Kooy gained postdoctoral research experience at Cambridge University and at the Salk Institute in California. In 2021 van der Kooy was elected to the Academy of Science Royal Society of Canada.
In 1981, he became an assistant professor, was promoted to associate professor in 1986, and has served as professor in the department of anatomy and cell biology at the University of Toronto[1] from 1991 until 2002, when he became a professor in the department of medical genetics and microbiology.[2] His lab is the Neurobiology Research Group.[3]
His lab in the Terrence Donnelly Centre for Cellular and Biomolecular Research carries out various neuroscience and developmental biology research projects. In 1994 his paper on neural stem cells in the adult mammalian forebrain was published in the journal Neuron. This work first established that adult mammalian neural stem cells were located in the subependyma of the forebrain lateral ventricle, where two types of lineage related precursor cells, progenitor cells and stem cells, were shown to be present. Proliferation of these cell types were characterized in further experiments that were reported in articles in Development and the Journal of Neuroscience. Of note, van der Kooy's lab produced the first report of stem cells in the adult mammalian eye, published in 2000 in Science. Further work, which was published in the journal, Neuron, 2001, documented how embryonic stem cells were shown to differentiate directly to neural stem cells through a default mechanism. Van der Kooy's lab continues to investigate the nature of stem cells, embryonic and adult, the concept of immortal cells, and the differentiation of embryonic stem cells, capable of forming any tissue in the body, to neural stem cells.
A report published in Science by van der Kooy's research group demonstrated that BDNF, when infused into the ventral tegmental area (VTA), can induce an opiate-dependent-like reward state in animals in the absence of opiate administration.
Previous studies have demonstrated that the opiatereward is mediated by a dopamine-independent reward system in nondependent animals, and by a dopamine-dependent reward system in dependent animals. In the present study, infusions of BDNF into the VTA were able to shift opiate reward from a dopamine-independent system to a dopamine-dependent system. This switch is mediated through a specific change in GABA-A receptors in the VTA from inhibitory to excitatory signaling in response to increased BDNF.
This work suggests that BDNF may play a critical role in mediating the shift to a drug-dependent motivational state, a crucial step in the pathogenesis of drug addiction.
Based on his experiments with human cadaveric pancreata, van der Kooy holds theorizes that there exists an adult stem cell in the pancreas.[4]
A neurotransmitter is a signaling molecule secreted by a neuron to affect another cell across a synapse. The cell receiving the signal, or target cell, may be another neuron, but could also be a gland or muscle cell.
Dopamine is a neuromodulatory molecule that plays several important roles in cells. It is an organic chemical of the catecholamine and phenethylamine families. Dopamine constitutes about 80% of the catecholamine content in the brain. It is an amine synthesized by removing a carboxyl group from a molecule of its precursor chemical, L-DOPA, which is synthesized in the brain and kidneys. Dopamine is also synthesized in plants and most animals. In the brain, dopamine functions as a neurotransmitter—a chemical released by neurons to send signals to other nerve cells. Neurotransmitters are synthesized in specific regions of the brain, but affect many regions systemically. The brain includes several distinct dopamine pathways, one of which plays a major role in the motivational component of reward-motivated behavior. The anticipation of most types of rewards increases the level of dopamine in the brain, and many addictive drugs increase dopamine release or block its reuptake into neurons following release. Other brain dopamine pathways are involved in motor control and in controlling the release of various hormones. These pathways and cell groups form a dopamine system which is neuromodulatory.
The mesolimbic pathway, sometimes referred to as the reward pathway, is a dopaminergic pathway in the brain. The pathway connects the ventral tegmental area in the midbrain to the ventral striatum of the basal ganglia in the forebrain. The ventral striatum includes the nucleus accumbens and the olfactory tubercle.
The nucleus accumbens is a region in the basal forebrain rostral to the preoptic area of the hypothalamus. The nucleus accumbens and the olfactory tubercle collectively form the ventral striatum. The ventral striatum and dorsal striatum collectively form the striatum, which is the main component of the basal ganglia. The dopaminergic neurons of the mesolimbic pathway project onto the GABAergic medium spiny neurons of the nucleus accumbens and olfactory tubercle. Each cerebral hemisphere has its own nucleus accumbens, which can be divided into two structures: the nucleus accumbens core and the nucleus accumbens shell. These substructures have different morphology and functions.
Brain-derived neurotrophic factor (BDNF), or abrineurin, is a protein that, in humans, is encoded by the BDNF gene. BDNF is a member of the neurotrophin family of growth factors, which are related to the canonical nerve growth factor (NGF), a family which also includes NT-3 and NT-4/NT-5. Neurotrophic factors are found in the brain and the periphery. BDNF was first isolated from a pig brain in 1982 by Yves-Alain Barde and Hans Thoenen.
The ventral tegmental area (VTA), also known as the ventral tegmental area of Tsai, or simply ventral tegmentum, is a group of neurons located close to the midline on the floor of the midbrain. The VTA is the origin of the dopaminergic cell bodies of the mesocorticolimbic dopamine system and other dopamine pathways; it is widely implicated in the drug and natural reward circuitry of the brain. The VTA plays an important role in a number of processes, including reward cognition and orgasm, among others, as well as several psychiatric disorders. Neurons in the VTA project to numerous areas of the brain, ranging from the prefrontal cortex to the caudal brainstem and several regions in between.
Samuel Weiss is a Canadian neurobiologist.
The olfactory tubercle (OT), also known as the tuberculum olfactorium, is a multi-sensory processing center that is contained within the olfactory cortex and ventral striatum and plays a role in reward cognition. The OT has also been shown to play a role in locomotor and attentional behaviors, particularly in relation to social and sensory responsiveness, and it may be necessary for behavioral flexibility. The OT is interconnected with numerous brain regions, especially the sensory, arousal, and reward centers, thus making it a potentially critical interface between processing of sensory information and the subsequent behavioral responses.
The reward system is a group of neural structures responsible for incentive salience, associative learning, and positively-valenced emotions, particularly ones involving pleasure as a core component. Reward is the attractive and motivational property of a stimulus that induces appetitive behavior, also known as approach behavior, and consummatory behavior. A rewarding stimulus has been described as "any stimulus, object, event, activity, or situation that has the potential to make us approach and consume it is by definition a reward". In operant conditioning, rewarding stimuli function as positive reinforcers; however, the converse statement also holds true: positive reinforcers are rewarding.
SRY -box 2, also known as SOX2, is a transcription factor that is essential for maintaining self-renewal, or pluripotency, of undifferentiated embryonic stem cells. Sox2 has a critical role in maintenance of embryonic and neural stem cells.
Neurogenins are a family of bHLH transcription factors involved in specifying neuronal differentiation. It is one of many gene families related to the atonal gene in Drosophila. Other positive regulators of neuronal differentiation also expressed during early neural development include NeuroD and ASCL1.
Addiction is a state characterized by compulsive engagement in rewarding stimuli, despite adverse consequences. The process of developing an addiction occurs through instrumental learning, which is otherwise known as operant conditioning.
Epigenetic regulation of neurogenesis is the role that epigenetics plays in the regulation of neurogenesis.
Lorenz Studer is a Swiss biologist. He is the founder and director of the Center for Stem Cell Biology at Memorial-Sloan Kettering Cancer Center in New York City. He is a developmental biologist and neuroscientist who is pioneering the generation of midbrain dopamine neurons for transplantation and clinical applications. His expertise in cell engineering spans a wide range of cells/tissues within the nervous system geared toward disease modeling and exploring cell replacement therapy. Currently, he is a member of the Developmental Biology Program and Department of Neurosurgery at Memorial Sloan-Kettering Cancer Center and a Professor of Neuroscience at Weill Cornell Medical College in New York City, NY.
Samantha Yammine is a Canadian neuroscientist and science communicator. She completed her PhD in 2019 at the University of Toronto.
Çağhan Kızıl is a Turkish/German neuroscientist and geneticist, and Associate Professor of Neurological Sciences at the Taub Institute for Research on Alzheimer's Disease and the Aging Brain at the Columbia University Vagelos College of Physicians and Surgeons Columbia University Irving Medical Center.
Ream Al-Hasani is a British neuroscientist and pharmacologist as well as an assistant professor of anesthesiology at Washington University in St. Louis. Al-Hasani studies the endogenous opioid system to understand how to target it therapeutically to treat addiction, affective disorders, and chronic pain.
Camilla Bellone is an Italian neuroscientist and assistant professor in the Department of Basic Neuroscience at the University of Geneva, in Switzerland. Bellone's laboratory explores the molecular mechanisms and neural circuits underlying social behavior and probes how defects at the molecular and circuit level give rise to psychiatric disease states such as Autism Spectrum Disorders.
Ilana B. Witten is an American neuroscientist and professor of psychology and neuroscience at Princeton University. Witten studies the mesolimbic pathway, with a focus on the striatal neural circuit mechanisms driving reward learning and decision making.
Lauren Orefice is an American neuroscientist and assistant professor in the Department of Molecular Biology at Massachusetts General Hospital and in the Department of Genetics at Harvard Medical School. Orefice has made innovative discoveries about the role of peripheral nerves and sensory hypersensitivity in the development of Autism-like behaviors. Her research now focuses on exploring the basic biology of somatosensory neural circuits for both touch and gastrointestinal function in order to shed light on how peripheral sensation impacts brain development and susceptibility to diseases like Autism Spectrum Disorders.
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