Brain Ponderings podcast with Mark Mattson

University of Cambridge Professor Trevor Robbins is a highly cited neuroscientist who has made major contributions to understanding how neuronal circuits and neurotransmitters control behaviors in health and brain disorders. In this episode I talk with Trevor about obsessive-compulsive disorder (OCD) an often debilitating mental disorder in which the affected person exhibits repetitive behaviors that interfere with their lives. He talks about studies in humans and animal models that point to problems in the communication of the frontal lobes (which function in cognitive control and decision-making) with the basal ganglia (which mediates habitual / automatic body movements).  We also talk about treatments for OCD which involve drugs that increase serotonin levels at synapses and, in severe OCD cases, deep brain stimulation or surgical excision of the cingulate cortex. LINKS Trevor Robbins webpage: https://www.neuroscience.cam.ac.uk/directory/profile.php?Trevor Trevor Robbins publications on PubMed: https://pubmed.ncbi.nlm.nih.gov/?term=robbins+tw&sort=date&size=200 Review article on OCD: https://www.cell.com/action/showPdf?pii=S0896-6273%2819%2930073-X Review article on cognitive control and executive function tests: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8617292/pdf/41386_2021_Article_1132.pdf Recent article on delayed development of PFC and mental disorders: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10202801/pdf/41591_2023_Article_2317.pdf

University of Cambridge Professor Trevor Robbins is a highly cited neuroscientist who has made major contributions to understanding how neuronal circuits and neurotransmitters control behaviors in health and brain disorders. In this episode I talk with Trevor about obsessive-compulsive disorder (OCD) an often debilitating mental disorder in which the affected person exhibits repetitive behaviors that interfere with their lives. He talks about studies in humans and animal models that point to problems in the communication of the frontal lobes (which function in cognitive control and decision-making) with the basal ganglia (which mediates habitual / automatic body movements).  We also talk about treatments for OCD which involve drugs that increase serotonin levels at synapses and, in severe OCD cases, deep brain stimulation or surgical excision of the cingulate cortex. LINKS Trevor Robbins webpage: https://www.neuroscience.cam.ac.uk/directory/profile.php?Trevor Trevor Robbins publications on PubMed: https://pubmed.ncbi.nlm.nih.gov/?term=robbins+tw&sort=date&size=200 Review article on OCD: https://www.cell.com/action/showPdf?pii=S0896-6273%2819%2930073-X Review article on cognitive control and executive function tests: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8617292/pdf/41386_2021_Article_1132.pdf Recent article on delayed development of PFC and mental disorders: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10202801/pdf/41591_2023_Article_2317.pdf

Imagine a world in which everyone got along and cared for the well-being of everyone else. In this episode I talk with Professor Rob Malenka of Stanford University about the neural circuits and neurochemicals involved in prosocial behaviors and empathy.  Malenka’s laboratory has used cutting-edge technologies to identify the brain regions and specific synapses that mediate prosocial behaviors and how MDMA enhances these behaviors.  He also talks about fascinating experiments which showed that neurons in a brain region called the anterior cingulate cortex mediate empathy-like behaviors in mice.  Malenka’s research is leading to new insights into how we interact with other people and how these interactions can be more rewarding and productive. We also talk about the neurobiology of addiction including the recent epidemic of food addiction and obesity.  LINKS Professor Malenka’s Stanford profile:  https://med.stanford.edu/profiles/robert-malenka Review article on the neurobiology of prosocial behavior: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8169714/pdf/nihms-1648144.pdf Oxytocin and reward: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6214365/pdf/nihms-989254.pdf Prosocial and rewarding properties of MDMA: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7123941/pdf/nihms-1565640.pdf Social transfer of pain and analgesia: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7952019/pdf/nihms-1672720.pdf Food addiction: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8035198/pdf/41467_2021_Article_22430.pdf

Every year humans consume approximately 10 million tons of crustaceans – crabs, lobsters, shrimp, and crayfish.  In order to grow these creatures must shed their hard exoskeleton in a remarkable process called molting.  Molting is controlled by a neuropeptide which is released into the blood and acts to suppress the production of a steroid molting hormone produced in the Y organ. In this episode Professor Don Mykles of Colorado State University talks about the remarkable process of molting and the cellular and molecular processes that control the production of the molting hormone and its actions on tissues in the body. Mykles’ laboratory discovered that the mTOR signaling pathway is of fundamental importance in the control of molting. This of considerable interest because mTOR is believed to play pivotal roles in neuroplasticity, aging, and developmental brain disorders in humans. LINKS: CSU Crab Lab webpage: https://mykleslab.biology.colostate.edu/researchers_mykles.html Review article on the neuroendocrine control of molting: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8256442/pdf/fendo-12-674711.pdf The ‘CrusTome’: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10320764/pdf/jkad098.pdf  

In this episode I talk with Dr. Ginger Campbell about the value for students, educators, and society of K-12 neuroscience education.  We also discuss potential approaches for and barriers to incorporating neuroscience into existing curricula.  Links: Article on neuroeducation for K-12 students: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4281050/pdf/june-13-8.pdf Article on neuroeducation for teachers: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8678470/pdf/fpsyg-12-752151.pdf Dr. Campbell’s Brain Science podcast: https://brainsciencepodcast.com/

Schizophrenia is an unusual brain disorder in that its dramatic symptom of psychosis (delusions and hallucinations) occurs seemingly spontaneously in young adults between the ages of 18 and 30. Alterations in dopaminergic, glutamatergic, and GABAergic neurons are implicated in schizophrenia and drugs that inhibit dopamine receptors are prescribed for patients. In this episode Professor Daniel Weinberger, Director of the Lieber Institute at Johns Hopkins University, talks about the importance of genetics, the environment of the developing fetus in the mother’s womb, and the placenta in determining whether or not a person develops schizophrenia. Collectively, the discoveries of Dr. Weinberger and others suggest that avoiding infections and maintaining a healthy lifestyle during pregnancy may reduce the risk of a child developing schizophrenia.   Links: Lieber Institute:  https://www.libd.org/ Review articles on schizophrenia: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7666011/pdf/nihms-1589556.pdf file:///Users/markmattson/Downloads/nrn.2017.125%20(1).pdf https://www-annualreviews-org.proxy1.library.jhu.edu/doi/pdf/10.1146/annurev-clinpsy-081219-103805 Schizophrenia risk genes: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10104472/pdf/sciadv.ade2812.pdf Placenta and schizophrenia: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10185564/pdf/41467_2023_Article_38140.pdf

Most people are familiar with the ultrasound imaging used to visualize in the body such as muscles and tendons, organs, and developing fetuses in the mother’s womb.  The sound/pressure waves generated by ultrasound are also used in physical therapy and the disruption of kidney stones. In this episode I talk with Professor Jurgen Götz at the University of Queensland about how ultrasound can affect neuronal network activity in the brain and can also be used to enhance the delivery into the brain of large molecules such as antibodies and neurotrophic factors.  Much of our discussion revolves around the potential use of ultrasound in Alzheimer’s disease.  LINKS: Professor Götz’ lab page: https://qbi.uq.edu.au/profile/1513/j%C3%BCrgen-goetz Review article on ultrasound: https://www-sciencedirect-com.proxy1.library.jhu.edu/science/article/pii/S0896627323001228 Preclinical studies of ultrasound therapy for memory enhancement and Alzheimer’s disease: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9221310/ https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8760044/pdf/41380_2021_Article_1129.pdf https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5405237/

In this episode I preview the book SCULPTOR AND DESTROYER’S coverage of the involvement of glutamate as a ‘destroyer’ of neuronal circuits and people’s lives in epilepsy, stroke, Alzheimer’s disease, Parkinson’s disease, depression, schizophrenia and other neurological disorders. I also talk about the central roles of the neurotransmitter glutamate in the actions of drugs of abuse, psychedelics, and of drugs used to treat neurological disorders. This episode also describes a chapter that considers how people can influence their glutamatergic systems in ways that optimize brain performance and protect against neurological disorders. Links to SCULPTOR AND DESTROYER: https://mitpress.mit.edu/9780262048187/sculptor-and-destroyer/ https://www.amazon.com/Sculptor-Destroyer-Glutamatethe-Important-Neurotransmitter/dp/0262048183?source=ps-sl-shoppingads-lpcontext&ref_=fplfs&psc=1&smid=ATVPDKIKX0DER

The long anticipated book SCULPTOR AND DESTROYER – Tales of Glutamate – the Brain’s Most Important Neurotransmitter written by myself, published by the MIT Press, and distributed by Penguin Random House will soon be released (August, 2023) and available at all major book outlets.  The book can be preordered before its release. In this episode I describe the roles of  ‘sculptor’ glutamate in evolution, brain development, learning and memory, and energy allocation and metabolism.  In the subsequent episode I preview the book’s coverage of the involvement of glutamate as a ‘destroyer’ of neuronal circuits and people’s lives in epilepsy, stroke, Alzheimer’s disease, Parkinson’s disease, depression, schizophrenia and other neurological disorders. I also talk about the central roles of the neurotransmitter glutamate in the actions of drugs of abuse, and of drugs used to treat neurological disorders. The second episode also includes a chapter that considers how people can influence their glutamatergic systems in ways that optimize brain performance and protect against neurological disorders. Links to SCULPTOR AND DESTROYER: https://mitpress.mit.edu/9780262048187/sculptor-and-destroyer/ https://www.amazon.com/Sculptor-Destroyer-Glutamatethe-Important-Neurotransmitter/dp/0262048183?source=ps-sl-shoppingads-lpcontext&ref_=fplfs&psc=1&smid=ATVPDKIKX0DER

Obesity and diabetes adversely affect learning and memory and increase the risk of dementia.  Professor Alexis Stranahan at the Medical College of Georgia has shown that visceral (abdominal) fat adversely affects the function and plasticity of neural circuits in the hippocampus whereas subcutaneous fat has beneficial effects on these circuits. Using mouse models of diet-induced or genetic obesity and transplantation of visceral or subcutaneous fat her laboratory found that obesity causes immune cells that accumulate in visceral fat to produce the pro-inflammatory cytokine IL-1beta. The IL-1beta then acts on microglial cells in the brain in ways that impair cognition. On the other hand subcutaneous fat has beneficial effects on cognition.  Exercise can counteract the adverse effects of visceral fat and enhance the beneficial effects of subcutaneous fat.  In this episode Professor Stranahan talks about this research and its implications for enhancing brain health..  LINKS: Stranahan Lab webpage: https://www.augusta.edu/mcg/dnrm/faculty/stranahan.php Review article: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8958382/pdf/nihms-1783794.pdf  Visceral fat and IL1-beta: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3921429/pdf/zns2618.pdf https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7108893/pdf/jci-130-126078.pdf Beige fat and cognition: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8324783/pdf/41467_2021_Article_24540.pdf Blood – brain barrier breakdown: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5363667/pdf/10.1177_0271678X16642233.pdf