Brain Ponderings podcast with Dr. Mark Mattson

Psychologist Richard Petty has been investigating the determinants of people's attitudes, and the situational and individual difference factors responsible for changes in beliefs, attitudes and behaviors. In this episode I talk with Professor Petty about the factors contributing to the recent spike in anti-science attitudes with a focus on identity politics and internet information bubbles. We also discuss how confidence in science can be increased. LINKS: Professor Petty's wepage: https://richardepetty.com/home/ PNAS article "Why are people antiscience, and what can we do about it?" https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9335320/pdf/pnas.202120755.pdf Article: "The neuroscience of persuasion": https://www.tandfonline.com/doi/epdf/10.1080/17470919.2016.1273851?needAccess=true&role=button

The neural cells in the retina of the eye capture and processes two-dimensional images of our world and send impulses via the optic nerve to the visual cortex where perception of the images occurs. Jeremy Nathans of Johns Hopkins University identified the genes encoding the light-sensitive proteins (opsins) in rod and cone photoreceptors and the molecular basis of color vision. He has made major contributions to understanding how the retina normally develops and functions, and he has elucidated the causes of several diseases of the eye including macular degeneration, retinitis pigmentosa, and Norrie disease. Here he talks about retinal phototransduction, evolution of the eye, and 'Wnt' and 'Frizzled' proteins that control the growth of blood vessels in the retina. Professor Nathan's research is revealing new approaches for therapies for genetic and age-related diseases of the eye. LINKS: Professor Nathan webpage: https://neuroscience.jhu.edu/research/faculty/61 Evolution and physiology of human color vision: https://www.cell.com/action/showPdf?pii=S0896-6273%2800%2980845-4 Frizzled in development and disease: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5103317/pdf/nihms826696.pdf Signaling pathways in neurovascular development: https://www-annualreviews-org.proxy1.library.jhu.edu/doi/pdf/10.1146/annurev-neuro-111020-102127 Gene therapy for diseases of the retina: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5983345/pdf/jci-128-120429.pdf

Among the more than 8 million species of animals one kills upwards of 600,000 people every year, most of which are children. By transferring an infectious agent into a human's blood female Anopheles gambiae mosquitos cause malaria. Here Chris Potter at Johns Hopkins University talks about his research that is revealing how the nervous system of mosquitos senses the presence of a human and decides whether or not to bite. His research is advancing understanding of the cellular and molecular organization and function of the mosquito brain, and is contributing to the development of new effective and safe insect repellents. He also talks about the promise and potential unintended consequences of genetic engineering technologies, such as gene drives, aimed at eliminating mosquito populations. LINKS Professor Potter's Labpage: https://potterlab.johnshopkins.edu/ Review article: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8256107/pdf/bjab021.pdf Olfactory centers in the mosquito brain: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5063964/pdf/ncomms13010.pdf Insect repellents: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6832857/pdf/nihms-1539869.pdf Gene drives: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8344398/pdf/41576_2021_Article_386.pdf Impact of climate change on mosquito-borne disease: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9334478/pdf/40121_2022_Article_647.pdf

The structure of neuronal networks is remarkably complex and dynamic. Professor Shelley Halpain has been at the forefront of research aimed at understanding how the brain's "neuroarchitecture" is established during development and changes in response to synaptic activity (neuroplasticity). Here she talks about the 'cytoskeleton' of neurons which consists of dynamic protein polymers of actin (microfilaments) and tubulin (microtubules), and how the polymerization state of these cytoskeletal proteins is controlled by the excitatory neurotransmitter glutamate and the calcium ion (Ca2+). Working with her students and collaborators Professor Halpain has elucidated roles for proteins that control actin or tubulin polymerization in the formation and adaptive modification of neuronal circuits. Such structural modifications play fundamental roles in the enduring changes in neuronal circuits involved in learning and memory. Interestingly, one of these proteins (INF2) mediates a process called 'actinification' which functions as an adaptive stress response that can prevent the death of neurons in conditions such as stroke and epileptic seizures. LINKS: Professor Halpain's Labpage: https://biology.ucsd.edu/research/faculty/shalpain Review article on Neuron Navigators: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9877351/pdf/fnmol-15-1099554.pdf Actinification and neuroprotection: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9558009/pdf/41467_2022_Article_33268.pdf Navigator control of growth cone internalization of neurotrophin receptors: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9561856/pdf/mbc-33-ar64.pdf Regulation of actin microfilaments by glutamate: https://www.jneurosci.org/content/jneuro/18/23/9835.full.pdf

Not only are obesity, insulin resistance, and chronic stress bad for peripheral organ systems but they can also wreak havoc on neuronal networks in the brain. Here Professor Larry Reagan talks about research showing that insulin acts directly on neurons in the brain and thereby plays important roles in synaptic plasticity and learning and memory. Neurons become unresponsive to insulin in obesity and diabetes and this neuronal insulin resistance may contribute to neuronal circuit dysfunction and damage in Alzheimer's disease. Elevated levels of the adrenal stress hormone cortisol also contributes to the adverse effects of insulin resistance and diabetes on the brain. Regular exercise, healthy dietary and sleep habits, and avoidance of chronic stress can prevent and reverse insulin resistance and excessive production of cortisol. LINKS: Professor Reagan's lab page: https://sc.edu/study/colleges_schools/medicine/about_the_school/faculty-staff/reagan_larry.php Review articles on brain insulin and leptin resistance: file:///Users/markmattson/Downloads/nrn4019%20(1).pdf https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8642294/pdf/nihms-1756570.pdf https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5988909/pdf/nihms927597.pdf Original research articles: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4613975/pdf/db150596.pdf https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8252121/pdf/main.pdf https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3774048/pdf/nihms285696.pdf

Marten Scheffer is a Dutch mathematician and ecologist who has made major contributions to modeling of complex systems. While he is best known for his work on catastrophic shifts in ecosystems and climate, he has more recently been applying dynamical systems theory to major brain-based problems of individual brains (e.g., belief traps and mental illness) and societies (e.g., inequality and fragility of democracies). Here I talk with Marten about features of dynamical systems – tipping points, basins of attraction, resilience…) and how systems modeling can be used to understand, evaluate, and intervene in detrimental ways of thinking and interacting with others. Links: Catastrophic shifts in ecosystems: file:///Users/markmattson/Downloads/35098000.pdf Early warning signals: file:///Users/markmattson/Downloads/nature08227%20(1).pdf Belief traps: file:///Users/markmattson/Downloads/pnas.2203149119%20(1).pdf Cognitive distortions: file:///Users/markmattson/Downloads/pnas.2102061118.pdf Shifts in rationality in language: file:///Users/markmattson/Downloads/pnas.2107848118.pdf

Despite many advances in neuroscience the fundamental question of how brains make computations is as yet unanswered. Progress has been hindered by the inabilities to monitor activities of large numbers of neurons during natural behaviors and to determine the structures and synaptic connections of all neurons involved in circuits mediating computations. Recent progress towards overcoming these hurdles has come from studies of Zebrafish in Professor Rainer Friedrich's laboratory at the Friedrich Miescher Institute in Basel Switzerland. Here Rainer talks about Zebrafish brain development, structure, and function. and how technological advances in genetics, brain imaging, dense reconstruction of neuronal connectivity, and virtual reality are being used to elucidate fundamental mechanisms by which neuronal circuits make computations. Links: Rainer Friedrich's lab page: https://www.fmi.ch/research-groups/groupleader.html?group=119 Virtual reality: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7100911/pdf/EMS85577.pdf Review article on Zebrafish behaviors: https://www-annualreviews-org.proxy1.library.jhu.edu/doi/pdf/10.1146/annurev-neuro-071714-033857 Odor coding: https://www.cell.com/action/showPdf?pii=S0960-9822%2817%2931452-5 Synaptic balance: https://www.cell.com/action/showPdf?pii=S0896-6273%2818%2930786-4 Dense circuit reconstruction: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5100684/pdf/sdata2016100.pdf

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