Brain Ponderings podcast with Mark Mattson

Professors Steve Roper and Nirupa Chaudhari at the University of Miami School of Medicine are pioneers in research on taste buds and the neurobiology of taste. The sense of taste evolved in ways that maximized the consumption of high energy foods while minimizing the consumption of potentially toxic chemicals in plants. Foods contain chemicals that interact with certain receptor proteins on the surface of electrically excitable cells in the taste buds of the tongue. Three different taste receptors have been identified and the ways in which they excite taste cells are known. Acting on a single type of receptor or multiple receptors tastes are categorized as bitter, sweet, sour, salty and umami. By mechanisms that remain to be established, information coming into the brain’s sensory cortex from taste receptors is combined with information from olfactory receptors in the nose to generate the perception of flavors. Remarkably, researchers have discovered that the receptors for bitter and sweet tasting chemicals are located not only in taste bud cells but also in cells throughout the body and brain. Links: Roper Lab webpage: https://umiamihealth.org/sylvester-comprehensive-cancer-center/research/labs/roper-lab Chaudhari Lab webpage: https://med.miami.edu/en/labs/chaudhari-lab Review articles on the neurobiology of taste: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5958546/pdf/nihms942554.pdf https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6462759/pdf/bjz013.pdf https://journals.physiology.org/doi/epdf/10.1152/physrev.00012.2022 Neuroscience text book: https://www.amazon.com/Neuroscience-Dale-Purves/dp/1605353809

Links: Lecture by Professor Herbison: https://www.youtube.com/watch?v=8ooMDuS6MDk Review articles:. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4785901/pdf/rstb20150115.pdf https://onlinelibrary-wiley-com.proxy1.library.jhu.edu/doi/pdf/10.1111/jne.13024 Recent original research articles. https://www.cell.com/action/showPdf?pii=S2211-1247%2822%2901813-7 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9718805/pdf/41467_2022_Article_35243.pdf

Amyotrophic lateral sclerosis (ALS) is the most common type of motoneuron disease and is characterized by progressive weakness and wasting of muscles. Most people with ALS will die within 3 years of the onset of symptoms. Professor Kevin Talbot of Oxford University has devoted his career to advancing an understanding of what goes wrong in ALS with the goal of discovering how it might be prevented and treated. Here I talk with Dr. Talbot about ALS including its epidemiology, genetic and environmental risk factors, cellular and molecular neurobiology, and emerging treatments. Links: Review articles: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9768794/pdf/41573_2022_Article_612.pdf https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8047135/pdf/fncel-15-653688.pdf Clinical Trials: https://clinicaltrials.gov/ct2/results?cond=als&term=&cntry=&state=&city=&dist= Lecture on ALS: https://www.youtube.com/watch?v=r-Ys6Obd814

Approximately one in every 4 Americans suffer from insufficient sleep which not only results in daytime tiredness and suboptimal brain function and an increased risk for depression, cognitive impairment, and Alzheimer’s disease.  In this episode Professor Ted Abel, Director of the Iowa Neurosciences Institute, talks about the adverse effects of sleep deprivation on neuronal circuits in the hippocampus that play critical roles in the formation, retention and recall of memories. Research in Dr. Abel’s laboratory has elucidated the molecular and cellular mechanisms of memory, how sleep deprivation alters those mechanisms, and how the effects of sleep deprivation can be mitigated.   Review articles on sleep, memory, and sleep deprivation: https://www.cell.com/action/showPdf?pii=S0960-9822%2813%2900848-8 https://www-clinicalkey-com.proxy1.library.jhu.edu/service/content/pdf/watermarked/1-s2.0-S0959438816301945.pdf?locale=en_US&searchIndex= https://www-clinicalkey-com.proxy1.library.jhu.edu/service/content/pdf/watermarked/1-s2.0-S0959438816301726.pdf?locale=en_US&searchIndex=   Pondering the Dynamic Sleeping Brain with Antoine Adamantidis: https://www.youtube.com/watch?v=XkaEBJwRhUo&t=298s

Klaus Miczek was born in Germany during World War II and grew up in Berlin where carnage from bombings were seen every day. Perhaps because of this profound example of the violence of the human species he became a neuroscientist whose research was aimed at understanding the neurobiology of aggression and violence with a goal of developing ways to reduce violent behaviors. Dr. Miczek is an endowed Professor of psychology, psychiatry, pharmacology and neuroscience at Tufts University. In this episode he describes what is currently known about the neuronal circuits and neurotransmitters involved in aggressive behaviors by providing a historical perspective on this fascinating yet understudied area of research.   Links:   Review articles: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3864145/pdf/nihms480918.pdf https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3380604/ Lecture on the neurobiology of aggression: https://www.youtube.com/watch?v=EtVfoIkVSu8

Multiple sclerosis (MS) is the most common autoimmune neurological disorder currently afflicting more than 1 million Americans. The disease begins early in life and typically manifests as intermittent periods of remission and relapse. Symptoms of MS - numbness, weakness, and vision problems – result  from loss of insulation of the axons of nerve cells in the brain and spinal cord. In this episode Dr. Amit Bar-Or a physician scientist at the University of Pennsylvania School of Medicine talks about the abnormalities in the immune and nervous systems that occur in MS and how research has led to very effective treatments for the vast majority of people with MS. Rapid advances in the treatment of MS is a major success story in the field of neurology. Links: National Multiple Sclerosis Society: https://www.nationalmssociety.org/ Review article on MS treatment: file:///Users/markmattson/Downloads/s41582-022-00675-0%20(2).pdf

Professor Ann Mckee has spent untold hours looking at the brains of former NFL players under the microscope.  She has found that nearly all of them exhibit abnormalities characterized by the presence of multiple islands of degenerating neurons surrounding small blood vessels. The affected neurons contain an abnormal (hyperphosphorylated) form of the protein Tau. The severity of the brain pathology is correlated with how long the individual played football and so the cumulative number of hits to the head they experience. CTE pathology occurs prominently in the prefrontal cortex a brain region that is important for control of emotions, working memory, and decision-making. Prior to their death these players exhibit behavioral abnormalities including outbursts of anger, confusion, poor decision-making, and depression. Dr. Mckee talks about her efforts to: understand how the disease develops, how it might be diagnosed early in the disease process, and potential ways of reducing risk for and treating this devastating brain disease.   Links: Boston University CTE Center: https://www.bu.edu/cte/about/leadership/ann-mckee-md/ PBS Frontline documentary ‘League of Denial’: https://www.youtube.com/results?search_query=league+of+denial CTE Diagnosis: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8166432/pdf/NEUROLOGY2020137927.pdf CTE in NFL players: file:///Users/markmattson/Downloads/jama_mez_2017_oi_170072%20(1).pdf CTE neuropathology: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5028120/pdf/nihms810306.pdf

Neuronal networks in the prefrontal cortex mediate our thoughts and control our actions and emotions.  Professor Amy Arnsten of Yale University talks about the research that has established the normal functions of prefrontal cortex neuronal circuits and how dysregulation of those neuronal circuits can result in depression, schizophrenia or Alzheimer’s disease.  The conversation revolves around a particular type of neuron with unique properties that are critical for working memory and reflective thought.   Links to videos on Yale Med School Youtube channel: https://www.youtube.com/watch?v=DEtnoiKGDwI&t=155s https://www.youtube.com/watch?v=TsQUeNuvIDY https://www.youtube.com/watch?v=wa3dWrszpEQ&t=22s     Links to some of professor Ansten’s reviews: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7983919/ https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7567669/   https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8203737/ https://pubmed.ncbi.nlm.nih.gov/23040817/ https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2907136/   Links to papers on Patricia Goldman-Rakic: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3767966/ https://doi.org/10.1016/S0896-6273(03)00685-8

In contrast to the dormancy of the body during sleep, neuronal networks in the brain exhibit complex patterns of activity that are important for the consolidation of memories of specific events experienced in the preceding day(s).  In this podcast I talk with professor Antoine Adamantidis at the University of Bern in Switzerland whose laboratory is revealing the nature of the activities of individual neurons and neuronal networks during sleep – wake cycles.  Using cutting-edge “optogenetic” technology his research has established the critical roles of neuron located in the hypothalamus and other brain regions in the control of sleep states and in the consolidation of memories. This research is leading to new approaches for improving sleep quality in ways that enhance daytime cognitive function, reduce the risk of psychiatric and age-related brain disorders, and improve recovery from a stroke or traumatic brain injury. Recent publications of Professor Adamantidis: Sleep and eating behavior: https://www-clinicalkey-com.proxy1.library.jhu.edu/service/content/pdf/watermarked/1-s2.0-S0166223621001831.pdf?locale=en_US&searchIndex= Narcolepsy: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7215265/pdf/zsz296.pdf Decoupling of cell body and dendrites during REM sleep: https://www-science-org.proxy1.library.jhu.edu/doi/epdf/10.1126/science.abk2734 Review articles on sleep: https://www-annualreviews-org.proxy1.library.jhu.edu/doi/pdf/10.1146/annurev-psych-010419-050815 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4286245/pdf/nihms648813.pdf

Dr. Victor Navarro at Harvard Medical School talks about the control of reproduction by neurons in the hypothalamus that produce a small protein called ‘kisspeptin’.  It turns out that kisspeptin neurons play critical roles in the regulation of the onset of puberty, the production of eggs and sperm, ovulation, and menopause. Energy (calorie) intake can have profound effects on reproduction. For example, severe caloric restriction during early life retards the onset of puberty and inhibits estrous cycles in adult females. On the other hand childhood obesity accelerates onset of puberty, and adult obesity can cause sexual dysfunction and infertility.  Dr. Navarro talks about the influence of energy balance on kisspeptin neurons and reproduction, and the potential of kisspeptin-based therapies for reproductive disorders. Links: Review articles: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8852368/pdf/nihms-1778788.pdf https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7159845/pdf/nihms-1569705.pdf   Talk on kisspeptin and sexual behaviors: https://www.youtube.com/watch?v=e5updgoSLGE