Brain Ponderings podcast with Mark Mattson

One of the most remarkable feats of biological ‘wizardry’ in the animal kingdom is the ability of some cephalopods (octopuses, squids, and cuttlefish) to rapidly change the color, patterning, and texture of their skin so as to blend in with their background. They accomplish these feats through the linking of neural circuits in the visual system and brain to muscle cells that control the dispersion of pigment in specialized skin cells called chromatophores. But the details of the neural circuitry and the computational processes that control the camouflaging process remain largely unknown. In this episode Columbia University neuroscientist Tessa Mont...

During vigorous exercise lactic acid (lactate) levels increase in the blood and during fasting and extended exercise the levels of the ketone BHB (b-hydroxybutyrate) increase. In this episode I talk with Stanford University professor Jonathan Long about his recent discovery that lactate and BHB in the blood are bound to the amino acid phenylalanine and that they (Lac-Phe and BHB-Phe) have beneficial effects on metabolic and brain health. Lac-Phe levels increase markedly in response to exercise in mice, humans, and race horses. Peripheral administration of Lac-Phe in suppresses food intake and reverses diet-induced obesity and insulin resistance in mice.  G...

White matter consists of bundles of long axons that convey information between neural circuits between different brain regions within and between brain hemispheres. These long axons are wrapped with many layers of lipid-rich membranes of oligodendrocytes (a type of glial cell) and it is this ‘insulation’ that enables rapid propagation of signals over long distances.  The axons in white matter consume high amounts of energy and their energy demand increases during extended physical exercise. In this episode Professor Carlos Matute talks about his interesting journey to become a neuroscientist and his fascinating discoveries concerning the function and dysfunction of oligo...

Michael Kreutz is Head of the Neuroplasticity Research Group at the Leibniz Institute for Neurobiology in Magdeburg Germany. Using powerful high resolution microscopy and molecular biology tools his laboratory has shown that autophagy occurs within synapses. Synaptic autophagy is stimulated by neural network activity and is critical for their maintenance and for learning and memory. Moreover, evidence suggests that conventional autophagy and exocytic autophagy prevent the abnormal accumulation of pathogenic proteins (Tau, TDP43, etc.) in neurodegenerative disorders. Pharmacological and lifestyle interventions that bolster synaptic autophagy may promote brain health and disease resistance. 

LINKS

Kreutz Laboratory: ht...

Belief in supernatural agents and other religious myths arose as a means of ‘explaining’ the unknown and as a tool for social cohesion and hierarchical control of civilizations. Their religiosity is major feature of a ‘believers’ self identity as well as their group identity. Compelling evidence from multiple types of studies have revealed the neurobiological foundations of beliefs in imaginary deities, an afterlife, and other religious myths. In this episode neuropsychologist Jordan Grafman talks about his research and related research showing that neural circuits in the prefrontal cortex convey religious beliefs much as they convey other beliefs (political, economic, etc.). P...

Neurological disorders involve aberrant neural network activity. New technologies are needed for establishing at a fine spatial and temporal resolution the nature of the altered network activity – and for restoring activity to or towards a healthy state. Professor Sri Sarma is an electrical engineer and neuroscientist who is at the forefront of this research field. Her research combines learning theory and control systems with neuroscience to develop novel approaches for understanding normal brain function and then developing brain – computer – electrophysiology feedback control systems to improve performance in health and disease.  Her research and technology development is advancing personalized treatments for epi...

Compelling evidence shows that consumption of high fructose corn syrup in soft drinks and ultraprocessed foods has contributed to the increases in obesity, diabetes, fatty liver disease, and dementia that has occurred during the past 50 years. Professor Richard Johnson’s research has been at the forefront of establishing how fructose adversely affects cellular energetics and function, and what happens to various organ systems with chronic consumption of fructose. Interestingly, cells can convert to glucose to fructose under certain conditions suggesting a roles for endogenously produced fructose in adverse effects of high glucose intake on health. Animal studies have shown th...

Major progress has recently been made in understanding the aging process at the molecular, cellular, and organ system levels. This knowledge is now being applied in preventative and interventional health care. Moreover, because of the severe burden of age-related diseases on societies governments are increasingly developing strategies to extend health span throughout their populations. In this episode Professor Brian Kennedy at the National University of Singapore provides a broad perspective on the field of aging research and its translation into actionable countermeasures. He talks about emerging research on ‘metabolic aging clocks’ and their applications to personalized  anti-aging strategies. His exper...

Remarkable progress has been made towards understanding of the molecular control of neurotransmitter release from presynaptic axon terminals and the responses of the postsynaptic neuron by neurotransmitters. We know that synaptic activity is required for learning and memory but the structural basis of a memory (an engram) remains unknown. Anton Maximov has made major contributions to understanding the molecular control of synaptic plasticity associated with learning and memory.  Here he talks about his research career journey which began in St. Petersburg Russia followed by postdoc training in Dallas Texas and then to the Scripps Research Institute where he is c...

The outer membrane of cells is comprised of a lipid bilayer consisting of phospholipids, cholesterol, arachidonic acid, omega-3 fatty acids, and others. Embedded in the membrane are various proteins that play roles critical to the survival and function of the cell. Examples of membrane proteins of particular importance for neurons are: ion channels and ion ‘pumps which control neuron excitability; glucose and ketone transporters which are critical for energy metabolism, and receptors for a myriad of neurotransmitters, neurotrophic factors, and other inter-cellular signaling molecules. In this episode chemistry Professor Allan Butterfield talks about research showing a pivotal role for fr...

A fascinating feature of interactions between two people is that neural network activity patterns in their brain can become synchronized. In this episode Francesco Papaleo talks about research studies in which activities of neuronal networks are recorded simultaneously in interacting humans or mice.  His work has recently focused on the role of interbrain synchronization in the prefrontal cortex in emotion recognition and empathy. He summarizes this research and its implications as follows:  

Interacting brains operate as an integrated system, with neural dynamics coevolving over time. Neuronal synchronization across brains has been observed in a range of species, in...

Neural networks in the brain are active 24/7 and so require a continuous supply of nutrients via the cerebral blood vessels. As we age the cerebral vascular system can become compromised resulting in damage to neurons and a consequent impairment of cognition. Cerebrovascular dementia is a major cause of morbidity and mortality in the elderly but can also occur in younger people as a consequence of genetic mutations. In this episode professor Thiruma Arumugam of LaTrobe University talk about the causes and consequences of cerebral small vessel disease. The good news is that there are several different measures people can...

William Brady deploys behavioral experiments, big data analytics, and natural language processing to elucidate how human psychology interacts with social media technology to affect morality, emotions, and decision-making.  Until very recently in their evolution any one human interacted with no more than a few dozen others during their lifetime. Moreover, those interactions were face-to-face. By its very nature social media is often subjecting our brains to situations for which they are not evolved to deal with properly. Politicians, large corporations, and ‘influencers’ with agendas are taking advantage of several features of social media to benefit themselves and their in-group (polit...

In this episode I provide an overview of the evidence that certain chemicals produced by plants and fungi are beneficial for brain function and health. I focus on the fact that the function of these phytochemicals or mycochemicals in the plants or mushrooms is to defend them from being consumed by insects and other animals.  We and other animals evolved mechanisms to tolerate the noxious chemicals.  We avoid too much of them because they have a bitter taste, and our cells respond to the chemicals by activating adaptive stress responses (antioxidant enzymes, protein chaperones, neurotrophic factors, etc). By these ho...

The vast majority of research on the cellular and molecular mechanisms of the storage and retrieval of memories has focused on the excitatory glutamatergic neurons that convey signals into and throughout the brain. However, recent research has revealed the importance of widespread oscillations in neural network activity (particularly gamma and theta frequencies) in cognition. In this episode Professor Dietmar Schmitz talks about features of short- and long-range neural connectivity and their roles in cognition with a focus on inhibitory GABAergic interneurons. Different subtypes of GABAergic neurons have different molecular signatures, shapes, electrophysiological properties, and connectivity patterns. These different GABAergic...

Research has shown that excessive dietary protein intake and high amounts of branch-chain amino acids (BCAA) in particular can accelerate aging and exacerbate chronic diseases of aging. In this episode University of Wisconsin Assoc. Professor Dudley Lamming talks about the cellular amino acid sensing mTOR pathway and its influences on aging and disease processes. The Lamming laboratory is making major contributions to establishing how amino acid intake affects cells and organ systems in health and disease. This research has important implications for optimizing health throughout the lifespan.  

LINKS

Lamming lab webpage: 

https://lamminglab.me...

Dopamine is best known as a neurotransmitter involved in the experiencing of pleasure and reward, and for its role in addiction to drugs, gambling, food, etc.  But dopamine is also very important in the brain’s ability to evaluate computational tradeoffs (cost versus benefit) and make decisions.  In this episode Roshan Cools a Professor of cognitive neuropsychiatry at Radbout University in the Netherlands talks about how dopamine normally controls the neuronal circuits in the striatum and prefrontal cortex that regulate motivation and cognitive control. By combining PET imaging to measure relative dopamine release with various cognitive control tasks and admi...

In this episode I talk with Professor Maryanne Garry at the University of Waikato New Zealand about several interrelated realms of human cognition that are fundamental to changes in the behaviors of individuals and social groups as influenced by electronic media and artificial intelligence.  Dr. Garry has devoted her career to understanding how memories of one’s past experiences can be distorted, how false information can become engrained in one’s system of beliefs. She talks about individual and collective memories, and the brain’s source monitoring systems and how they are influenced by group identity, repetition of information (whether...

It had long been thought that the brain was ‘immunologically privileged’ (physically separated from the immune system).  However, this dogma was overturned by a series of discoveries including those made by Professor Michal Schwartz at the Weizmann Institute. In this episode I talk with Michal about the different types of immune cells that are located in ‘immunological niches’ of the brain (choroid plexus, perivascular space, meninges..) and how these cells play critical roles in maintaining normal brain health and function (neurogenesis, synaptic plasticity, learning and memory). In addition, Michal tells us how the immune system is vital for healing and prote...

Throughout our waking hours neural networks in our brains are processing incoming information, particularly sights and sounds, integrating those inputs with stored information, making decisions, and executing responses. Staying on task requires that we attend to the details of the task while filtering out ‘noise’.  In this episode I talk with Diego Mendoza-Halliday at the University of Pittsburgh about visual working memory – what it is, what neuronal circuits are involved, and how it works. His experiments involve recording of neuronal activity in prefrontal cortex and other brain regions while individuals are performing visual working memory tasks. His findings have reveale...

Professor Thomas Hartung has made a major impact in biomedical research by developing and promoting alternatives to animal research. His efforts are leading to more ethical and efficient approaches to basic and applied research in the fields of environmental toxicology, drug development, and neuroscience. In this episode I talk with Thomas about two major flourishing technologies – brain organoids and artificial intelligence – and  how they are being rapidly incorporated into both basic and translational research.  He provides an historical perspective on the overzealous and unnecessary use of lab animals for toxicology and drug development and then delves into emerging research on ‘or...

Someday it may be possible to restore neuronal networks that have been lost or damaged by brain injury or in neurodegenerative disorders such as Alzheimer’s and Parkinson’s diseases. There are as many astrocytes in the human brain as there are neurons and the astrocytes generally do not die in brain injuries and neurodegenerative disorders. Professor Magdalena Götz has shown that astrocytes can be converted directly into neurons using molecular biology technologies to manipulate a few transcription factors that switch cell fate.  These new neurons grow and form synapses with each other and can integrate into functional neuron...

The Euclidean geometry that we learned in our primary education concerns man-made shapes such as rectangles, triangles, and perfect circles. However the shapes of molecules, cells, and organ systems (and their dynamic changes over time) are more complex. Some biological structures exhibit fractal geometry which is defined as “shapes and patterns that appear similar at different scales” (recursive iteration). Examples of biological structures exhibiting fractal geometry include the branches and roots of trees, blood vessels, lung airways, and the dendritic arbors of neurons. In this episode I talk with Antonio Di leva a neurosurgeon and neuroscientist at Macquarie University Scho...

Polyamines are small organic molecules that are acquired in the diet and can also be synthesized in cells. Spermidine is a polyamine that is increasingly recognized as playing important roles in counteracting aging. Foods with high amounts of spermidine include whole grains, broccoli, and natto (fermented soybeans). Professor Stephan Sigrist at the Free University of Berlin who is widely known for his fundamental contributions to understanding how specific proteins and their interactions control the rapid release and reuptake of neurotransmitters at the presynaptic active zone.  In this episode I talk with Stephan about his recent fascinating discoveries that have r...

In the moment most people can readily distinguish between information that is coming into the brain from their senses and what information their brain is generating. However, when recalling information stored in the brain’s neuronal networks the ability to distinguish between what was real and what was imagined becomes more problematic.  How does the brain keep track of what we actually experienced in the past and what we imagined happened?  In this episode Jon Simons who is Professor of Cognitive Neuroscience at the University of Cambridge talks about his research that is elucidating the neurobiological basis of reality moni...

In this episode Emory University and Chinese Academy of Sciences Professor Keqiang Ye talks about his fascinating and ground-breaking trail of discoveries that have revealed previously unknown mechanism responsible for the production and accumulation of damaging fragments of the APP and Tau proteins in Alzheimer’s disease (AD) and the alpha-synuclein protein in Parkinson’s disease (PD). He discovered an enzyme called AEP that cleaves Tau and alpha-synuclein into self-aggregating toxic fragments.  Eliminating or disabling AEP can prevent the disease process and preserve brain function in mouse models of AD and PD.  More recently, in a series of studies his la...

Among high income countries the United States spends the most on health care and yet has the lowest life expectancy. A high percentage of Americans suffer with chronic diseases including obesity, diabetes, cardiovascular disease, mental disorders, and Alzheimer’s or Parkinson’s diseases. There are several reasons why people living in the wealthiest country have poor health all attributable to unrestrained capitalism. In this episode I talk about issues with pharmaceutical industry that contribute to the overall poor quality of health and health care in America with a focus on drugs for neurological disorders.  Drug prices in the US are m...

In this episode I talk with Professor Jason Shepherd about his discoveries concerning a fascinating protein called Arc.  In response to synaptic activity Arc levels rapidly increase in postsynaptic dendrites as a result of local translation of the Arc mRNA in the dendrites. Arc plays a critical role in long-term memory although it is not necessary for learning. But perhaps the most interesting twist in the Arc story comes from the Shepherd labs discovery that Arc can self-assemble into highly ordered structures that are essentially identical to the capsids that form the coat of viruses. I talk with Jason a...

Among high income countries the United States spends the most on health care and yet has the lowest life expectancy. A high percentage of Americans suffer with chronic diseases including obesity, diabetes, cardiovascular disease, mental disorders, and Alzheimer’s or Parkinson’s diseases. There are several reasons why people living in the wealthiest country have poor health all attributable to unrestrained capitalism.  In this episode I talk about how large-scale monoculture crops used to produce addictive ultraprocessed sugars such as high fructose corn syrup adversely affect health including brain health. The widespread availability of such obesogenic high-calorie ultraprocessed foods at lo...

Humans have the amazing ability to instantly recognize the faces of hundreds or even thousands of people they have previously met or seen in pictures or movies. Studies of people with brain injuries that render them incapable of recognizing faces and recordings of neuronal activity in people during face recognition have shown that networks in the occipital and temporal lobes adjacent to the visual cortex mediate facial recognition.  Professor Bruno Rossion is at the forefront of research that is revealing the neurophysiological underpinnings of face recognition. By recording and stimulating neurons in the face recognition circuits of numerous research p...

In this final episode of the Bioenergetics and Brain Health series I talk about changes that occur in brain cells during normal aging, and in Alzheimer’s disease, Parkinson’s disease, and stroke with emphasis on alterations upstream and downstream of cellular energy metabolism. The episode concludes with examples of therapeutic interventions that target those age- and disease-related alterations. 

LINKS:

Hallmarks of Brain Aging

https://pmc.ncbi.nlm.nih.gov/articles/PMC6039826/pdf/nihms979409.pdf

Brain Energy Rescue:

https://pmc.ncbi.nlm.nih.gov/articles/PMC7948516/pdf/nihms-1624328.pdf

In this third podcast in the Bioenergetics and Brain Health series I talk about how intermittent exercise and fasting affect brain function, neuroplasticity, and resilience. Research has shown that both of these bioenergetic challenges can enhance learning and memory, improve mood, counteract aging, and protect neurons against injury and disease. I provide an overview of evidence that over periods of weeks and months cycling between challenge (exercise and fasting) and recovery (resting, eating, sleeping) periods stimulates the formation of new synaptic connections between neurons, increases neurogenesis, and bolsters neuronal stress resistance.  These adaptations of brain cells to bioenergetic challenges a...

This is the second in a series of presentations on the interrelationships between energy metabolism, brain function and resilience, and disease processes. In this episode I describe how mitochondria are moved about within axons and dendrites, how mitochondria divide, fuse with each other, and are eliminated when they become dysfunctional.  Importantly, mitochondria influence and respond to activity in neuronal networks in ways that optimize energy efficiency and promote the formation and maintenance of synapses between neurons. I also introduce the next presentation which will focus on how physical exercise and intermittent fasting affect brain function, plasticity, and resilience.

More than 40 percent of the human genome consists of retrotransposons which are DNA sequences related to retroviruses that can jump within the genome and have the ability to replicate although most are dormant.  In this episode Professor Josh Dubnau at the University of Stony Brook talks about endogenous retroviruses and retrotransposons and recent evidence that some of them are activated in neurons during brain aging and may play roles in the pathogenesis of ALS, frontotemporal dementia, and Alzheimer’s disease. Using the powerful molecular genetic tools in Drosophila models the Dubnau and his team have shown that activated retrotransposons can...

This is the fist in a short series of presentations on the interrelationships between energy metabolism, brain function and resilience, and disease processes. Overindulgent sedentary lifestyles are increasingly common with adverse consequences for trajectories of brain health in current and future generations. In this series I review findings from studies of humans and animals that are elucidating the cellular and molecular mechanisms by which energy intake and exercise affect structural and functional neuroplasticity. This topic is considered from a bioenergetic perspective with emphases on brain evolution, developmental neurobiology, adult neuroplasticity and disorders of mood and cognition.

Every day we communicate with and influence others via language, decision-making, and actions. The complexities of human social interactions and language begs the question of how the brain processes the relevant incoming information and then generates responses so rapidly and effortlessly. Neurosurgeon Ziv Williams and his team at Harvard Medical School have made major advances in answering these questions.  By recording the activities of hundreds of individual neurons in the brains of non-human primates in game-theory paradigms of social cooperation and conflict he has identified neurons in the prefrontal cortex that encode social agent identity. Moreover, by recording from n...

One in seven people experience migraine headaches while others suffer with even more debilitating cluster headaches. The causes of these headaches are not fully understood and current treatments provide only partial relief.  In this episode pharmacologist Antoinette van den Brink and neurologist Rolf Fronczek describe the clinical features of these headaches, the current understanding of their causes, and hormonal and environmental factors that can trigger the headaches. Drugs that inhibit the peptide CGRP and electrical stimulation of the occipital nerve are among treatments shown to be effective in reducing headache intensity or duration.

LINKS

University w...

Consciousness is one’s awareness of electrochemically conveyed information coming into the brain from the environment via sensory pathways or generated within the brain’s neuronal networks (i.e., thoughts). In popular culture ‘consciousness’ is often portrayed as a mysterious concept or process. However, research that examines the effects of anesthetics, sleep, brain injuries, and psychedelics on neuronal network activity using fMRI, EEG and other technologies is revealing the circuits and activity patterns that enable consciousness. In this episode University of Cambridge Professor Andrea Luppi talks about his research on the neurochemical and neural network level underpinnings of consciousness. His inte...

In this episode Richard Lu – a professor of pediatrics at the University of Cincinnati Chldren’s Hospital talks about a type of stem cell in the brain called oligodendrocyte progenitor cells (OPC). OPC normally differentiate into the oligodendrocytes that wrap around the axons of neurons providing insulation that greatly speeds up the propagation of electrical impulses. These cells also provide nutrients to neurons and produce proteins that promote the survival of the neurons.  But OPC can and unfortunately do become transformed into cancer cells.  Dr. Lu talks about the normal roles of OPC in brain development and how they can fo...

Arizona State University Professors Visar Berisha and Julie Liss have combined their expertise in engineering and speech communication to develop and apply novel automated speech analysis technology to the field of neurological disorders. Because of the complexity of human speech and the brain circuits involved speech analysis can provide a window into multiple domains of brain function.  In this episode they talk about their research and how speech analysis can be used as a tool for cross sectional and longitudinal studies of people with or a risk for brain dysfunction. Their published findings range from studies of NFL football p...