Brain Ponderings podcast with Mark Mattson

Olfaction, the most primitive of our senses, enables our brains to perceive thousands of different airborne chemicals. But it is not known how the outside olfactory world is coded in neuronal networks in the brain nor how those codes are evaluated in ways that result in behavioral responses to specific odors. Professor Bob Datta’s laboratory at Harvard is developing and using cutting-edge technologies to answer these questions. Here he talks about the different types of neurons and their spatial and function organization in the olfactory system, and how emerging 3D imaging and unsupervised machine learning technologies are enabling quantitative analysis of spontaneous and odor-evoked behaviors of animals in natural environments.   Links:  Datta Lab webpage: http://datta.hms.harvard.edu/ Review article: https://www-annualreviews-org.proxy1.library.jhu.edu/doi/pdf/10.1146/annurev-neuro-102119-103452 Recent publications from the Datta Lab: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9892006/pdf/41586_2022_Article_5611.pdf https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8758202/pdf/nihms-1757925.pdf https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7606807/pdf/nihms-1619406.pdf

In 2011 and 2014 Tony Wyss-Coray and his lab members published high-profile papers in which they used a procedure called parabiosis and blood transfusions to show that blood plasma from young animals can rejuvenate the brains of old mice and vice-versa. Moreover, they found that young plasma restores cognitive function in a mouse model of Alzheimer’s disease. Since then many other labs have confirmed this remarkable phenomena and Wyss-Coray and others have been working to identify the ‘rejuvenating factor’ or factors in young plasma. A recent preliminary clinical trial in which patients with Alzheimer’s were infused with plasma from young people generated promising results.  Here I talk with Tony about this exciting area of research.   Links:  Professor Wyss-Coray lab page: http://web.stanford.edu/group/twclab/cgi-bin/ Key publications: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3170097/pdf/nihms313001.pdf https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4224436/pdf/nihms632757.pdf https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5586222/pdf/nihms901457.pdf https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9387403/pdf/nihms-1827565.pdf

The environment and experiences of caregivers can affect the development of social skills in the infants they care for in ways that can result in enduring changes in behavior patterns. In this episode neuroscientist Maya Opendak at Johns Hopkins University talks about her research using experimental models of deprivation and adversity which is shedding light on the brain circuits altered by deprivation and maternal stress and the cellular and molecular mechanisms underlying those alterations.  Such fundamental information will be required to fully understand and therefore work towards optimization of the early life environments of infants and their caregivers.   Links: Dr. Opendak’s lab webpage: https://www.opendaklab.com/  Review article on animal models of early life adversity: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9385963/pdf/fnbeh-16-918862.pdf  Nature Communications 2020 – Adverse caregiving in infancy blunts neural processing of the mother: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7048726/pdf/41467_2020_Article_14801.pdf  Nature 2021 – rodents can acquire maternal behavior by social transmission. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8387235/pdf/41586_2021_Article_3814.pdf  Neuron 2021 – Bidirectional control of infant rat social behavior via dopaminergic innervation of the basolateral amygdala: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8988217/pdf/nihms-1745418.pdf

Professor Cynthia Moss has been studying the neurobiology of bat echolocation for more than three decades. Psychologist Daniel Kish became blind during the first year of his life and learned use echolocation to guide himself as he walks or rides a bike. Daniel is the founder of World Access For Blind and has devoted his life to enabling people with blindness excel in all aspects of life. In this episode Dr. Moss and Daniel talk about all things echolocation from bats hunting insects to people living in our communities.     Links to information on Professor Moss’s research: https://pbs.jhu.edu/directory/cynthia-moss/ https://www.youtube.com/watch?v=ay37PSIukwA https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9306857/pdf/HIPO-32-298.pdf https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7682551/ https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5896882/pdf/elife-29053.pdf https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6115611/pdf/fncel-12-00270.pdf   Links to information on Daniel Kish and his work:   https://visioneers.org/daniel-kish/ https://www.youtube.com/watch?v=uH0aihGWB8U https://waftb.net/ https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5578488/pdf/pcbi.1005670.pdf

Jean Lud Cadet is a neurologist and neuroscientist at the National Institute on Drug Abuse whose research is revealing why some people become addicted to methamphetamine while others do not, and how methamphetamine can damage and kill neurons resulting in long-lasting or even permanent impairments of learning and memory. His recent findings suggest that methamphetamine can cause enduring alterations in gene expression in neurons by mechanisms involving epigenetic mechanisms.  This research is providing insight into new approaches for identifying people at high risk for addiction and treating those who are already addicted.   Links:  Jean Lud Cadet webpage: https://irp.nida.nih.gov/staff-members/jean-lud-cadet/ Jean Lud Cadet on Wikepedia: https://en.wikipedia.org/wiki/Jean_Lud_Cadet METH epigenetics: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8535492/pdf/genes-12-01614.pdf METH addiction and potassium channels: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7865894/pdf/ijms-22-01249.pdf

Approximately 30% of people who are infected with COVID will experience long-lasting symptoms of impaired brain function including reduced ability to concentrate, impaired memory, confusion, depression and chronic fatigue.  These problems often last for many months beyond the time at which the SARS-CoV2 virus is no longer detectable in their nasal passages or blood. In this podcast Professor Daniel Martins-de-Souza talks about research from his laboratory and those of his collaborators published in the Proceedings of the National Academy of Sciences which provides evidence that SARS-CoV2 enters the brain where it infects astrocytes, a type of glial cell that normally plays important roles in brain energy metabolism, the regulation of cerebral blood flow, and the production and removal of several neurotransmitters. Their research reveals several approaches for the prevention and treatment of “neuroCOVID” including those that may prevent entry of the virus into astrocytes and those that may protect neurons against adverse effects of astrocyte infection.   Links Professor Martins-de-Souza’s research gate: https://www.researchgate.net/profile/Daniel-Martins-De-Souza-2 PNAS article: Morphological, cellular, and molecular basis of brain infection in COVID-19 patients. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9436354/pdf/pnas.202200960.pdf Review article on Long NeuroCOVID: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9537254/pdf/main.pdf

Harvard neuroscientist Michael Ferguson’s research is revealing the brain’s neuronal networks that mediate religious experiences and spirituality.  In this podcast he talks about his findings from functional brain imaging studies of devout Mormons and of people who exhibited profound changes in religiosity after having a brain injury resulting from surgery or accident.  I talk with him about the implications of his findings for brain evolution, psychiatric disorders, and new approaches for improving the health and welfare of individuals and societies.   Links: Dr. Ferguson lecture: https://www.youtube.com/watch?v=gmnYBEmB2i0&t=1662s   Relevant publications: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8714871/pdf/nihms-1735983.pdf https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5478470/pdf/nihms864583.pdf https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2660736/pdf/zpq4876.pdf  https://www-annualreviews-org.proxy1.library.jhu.edu/doi/pdf/10.1146/annurev-psych-120710-100334 Robert Sapolsky Lecture on Evolution and Religion: https://www.youtube.com/watch?v=4WwAQqWUkpI

Most of us have a clear sense of morality. We can distinguish behaviors that are right or appropriate from those that are wrong or inappropriate. We feel empathy for people in distress and feel guilt and remorse when our actions hurt others. However, research in psychiatry and psychology has shown approximately 1 in every 100 adults exhibit pathological immoral behaviors – a.k.a. “Psychopathy”.  Behavioral features of a psychopath include: superficial charm, grandiose sense of self-worth, pathological lying, being manipulative, lack of remorse or guilt, callousness/lack of empathy, failure to accept responsibility for their actions, impulsivity, irresponsibility, and criminal versatility. A person with psychopathy is much more likely to commit violent crimes than others. Indeed, approximately 30% of people incarcerated for murder are psychopaths.   Dr. James Blair is a neuroscientist who has been working to elucidate how the brains psychopaths might differ from brain of people without this problem. In particular he has been studying children with conduct disorder (CD) and callous unemotional traits because these children are at increased risk for psychopathy. Such children also often exhibit symptoms of ADHD. Here Dr. Blair talks about studies in which functional MRI was used to examine neuronal network activity in different brain regions of children with or without these behavioral problems. It turns out that the brain’s fear center – the amygdala – fails to respond normally when the children are shown images of the faces of people in distress. Moreover, there are abnormalities in the prefrontal cortex of children with conduct disorder which may help explain their failure to control their aggressive behaviors.  The good news is that most children with ADHD and CD benefit greatly from the  appropriate therapies.   Links: Lecture by Dr. Blair: https://www.youtube.com/watch?v=rORJxl1cPyM  Review articles on psychopathy and conduct disorder: file:///Users/markmattson/Downloads/s41572-021-00282-1.pdf file:///Users/markmattson/Downloads/s41572-021-00282-1.pdf

Approximately one in every fifty children is affected by autism spectrum disorder (ASD) and will require extra help from parents, teachers, and health professionals to reach their full potential.  Professor Matthew State, a psychiatrist and geneticist at the University of California San Francisco has made major contributions to the current understanding of the factors that determine whether or not a child will have an ASD. Here he talks about  the neurobiology of autism with a focus on research showing that genetics plays a major role in most instances of autism with gene mutations apparently occurring de novo in the genomes of the mother’s egg or the father’s sperm. These genetic aberrancies result in accelerated growth of brain cells and formation of synapses during brain development resulting in alterations in the activities of neuronal networks in brain regions involved in regulating social interactions and communication.  As the research on ASD progresses new approaches for treatment are emerging.  Links: Professor State’s UCSF webpage: https://profiles.ucsf.edu/matthew.state Lecture by Professor State: https://profiles.ucsf.edu/matthew.state  Review articles on autism: file:///Users/markmattson/Downloads/s41583-022-00576-7%20(2).pdf https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8163016/pdf/nihms-1704166.pdf https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6779523/pdf/nihms-1537205.pdf

Language pervades our lives. The ability to speak has allowed our species to pass knowledge between generations, articulate complex ideas, and build societies. How did brains evolve to enable this remarkable means of communication? Professor Erich Jarvis at Rockefeller University is using cutting edge technologies in neuroscience and genetics to provide answers to this question. In this podcast he talks about the neuronal circuits and genes involved in vocal learning in songbirds, and how they are related to the neurobiology of language in humans.   Lecture by Dr. Jarvis: https://www.youtube.com/watch?v=EAAr95eqd2c   Review articles: Evolution of vocal learning and spoken language. https://www-science-org.proxy1.library.jhu.edu/doi/epdf/10.1126/science.aax0287 The neural processing of human spoken language https://www-science-org.proxy1.library.jhu.edu/doi/epdf/10.1126/science.aax0288