Brain Ponderings podcast with Dr. Mark Mattson

In this episode I talk with Weill Cornell Medicine professor Tim Ryan about the local regulation of energy metabolism in synapses.   Tim and his colleagues use high resolution imaging of fluorescent probes that enable measurements of ATP and calcium in presynaptic terminals and postsynaptic dendrites of neurons in which energy substrates are manipulated. His lab has made several novel findings tha...

In Alzheimer's disease and other 'Tauopathies' the Tau protein (which normally controls the polymerization of microtubules) becomes hyperphosphorylated and self-aggregates into insoluble fibrils called 'neurofibrillary tangles' within neurons. Excessive phosphorylation of Tau by a kinase called GSK3 is implicated in neurofibrillary tangle formation and neuron death in Alzheimer's disease. The Span...

Ultraprocessed foods that contain high amounts of simple sugars (particularly high-fructose corn syrup), saturated fats, salt, and various chemicals that enhance taste and color. In this episode I talk with University of Michigan psychology professor Ashley Gearhardt about research showing that ultraprocessed foods are addictive and a major cause of poor metabolic health and chronic diseases in th...

In this episode – a role reversal. Mark is interviewed by Justin Lathia a professor at the Cleveland Clinic and former graduate student in Mark's lab. The podcast provides a whirlwind tour of Mark's early life and research career – from graduate and postdoc training in Iowa and Colorado, to research in his laboratories at the University of Kentucky and the National Institute on Aging. Justin also...

The combined efforts of neurologists, geneticists, molecular biologists, and electrophysiologists have identified genes in which rare mutations cause either extreme pain sensitivity or complete lack of pain sensation. The extreme pain syndromes include primary erythromelalgia and small fiber neuropathies that result painful extremities triggered pressure, touch, and heat. Three of these genes enco...

Optimal health depends critically on maintenance of an evolutionarily ancient circadian clock that ticks within all cells of the body and brain. Discovery of the genes that encode the core proteins of the molecular clock have revealed how the clock works and, importantly, how the clock influences health and resilience. Joseph Takahashi discovered the gene for CLOCK which is one of four proteins th...

In this episode I talk with MIT neuroscientist Ev Fedorenko about the neural networks that process language in the human brain, the relationships between the processing of language and thought, evolutionary perspectives on thinking versus communicating, and artificial intelligence systems as tools for advancing understanding of the neurobiology of language. To understand the neural networks of lan...

Vision loss is a major cause of disability throughout the world. While there are effective treatments for cataracts and for preventing glaucoma, there are numerous genetic disorders that cause degeneration of cells in the retina for which no treatments currently exist. Inherited retinal diseases can be caused by recessive (loss-of function) or dominant (gain-of-function) mutations in genes express...

It is well-established that neurons have a high energy (ATP) demand and that mitochondrial impairment can render neurons vulnerable to degeneration. However, surprisingly little is known about the involvement of mitochondria in the activation and plasticity of individual synapses. In this episode Vidhya Rangaraju, head of the Neuroenergetics Laboratory at the Max Planck Florida Institute for Neuro...

How does the brain rapidly integrate information coming our different senses with stored information, and their saliences, so as to make decisions and respond (or not)?   In this episode I talk with UCLA Professor Lucina Uddin who investigates the relationships between connectivity of different brain regions and cognition with an emphasis on brain development and disorders thereof. In this episode...

The amyloid precursor protein (APP) is a transmembrane protein and the source of the amyloid beta-peptide that accumulates in plaques in the brain in Alzheimer's disease. However, the normal function(s) of APP are uncertain. In this episode I talk with Bassem Hassan, a developmental neurobiologist and molecular biologist at the Paris Brain Institute who has made major contributions that advance an...

There are about 100 billion neurons and 100 trillion synaptic connections between them in the human brain. The activity of those neural networks is controlled by only a handful of major neurotransmitters and all neurons respond to the excitatory transmitter glutamate and the inhibitory neurotransmitter GABA. This poses a major problem for using drugs that block or activate neurotransmitter recepto...

Distributed throughout the brain are oligodendrocyte precursor cells (OPCs) capable of proliferating and differentiating into the oligodendrocytes that wrap around axons (myelination) thereby greatly increasing signal propagation in neural networks. OPCs are essential for axon myelination during brain development, can enhance myelination in response to neural network activity, and can remyelinate...

How do neural networks in the cerebral cortex transform incoming sensory information to generate perceptions of the world and elicit behavioral responses?   This question is being tackled in the laboratory UC Berkeley Professor Hillel Adesnik whose research program is aimed at understanding exactly how microcircuits in the cerebral cortex process sensory information to generate perceptions and dri...

Lipids (phospholipids, cholesterol, sphingolipids, ceramides, triglycerides, fatty acids, and others) play vital roles as the major building blocks of cell membranes and in energy metabolism, and cell signaling. University of Alberta cell biologist Maria Ioannou is using cutting-edge cell imaging and biochemistry technologies to elucidate how lipids are moved within and between cells, and how thos...

Interoception is a term used to describe the processes by which the brain detects, interprets, and responds adaptively to signals (pain, hunger, fatigue, etc.) coming from various organs in the body. In this episode University of Pennsylvania neuroscientist Nick Betley talks about recent research that has revealed key roles for relatively small numbers of neurons in the hypothalamus in interocepti...

Normally activity in the brain's neural networks is tightly regulated by the interplay between neuronal excitation by the neurotransmitter glutamate and inhibition by GABA. An epileptic seizure is a dramatic example of what can happen when an abrupt excitatory imbalance occurs. However, excitatory imbalances also occur during aging and contribute to the dysfunction and degeneration of neurons in A...

Stanford Professor Liqun Luo's laboratory investigates the mechanisms by which neural circuits in the brain are assembled during development and how this neuroarchitecture enables their functions throughout life. During the past 30 years his work has provided technical advances that enabled the establishment of roles for specific proteins in the formation of synaptic connections between individual...

The rapid psychedelic effects of the mushroom chemical psilocybin and its long-lasting mood-elevating effects are remarkable. While psilocybin and other psychedelics activate the serotonin 5HT2A receptor the nature of the functional and structural changes responsible for the dramatic effects of psychedelics on perception, mood, and cognition are unknown. In this episode Cornell University Professo...

Here I describe evidence that brain aging can be slowed by lifestyle choices that include exercise, moderation in energy intake, and consumption of plant-based diets.   LINKS https://pmc.ncbi.nlm.nih.gov/articles/PMC5913738/pdf/nihms958771.pdf https://www.cell.com/action/showPdf?pii=S1550-4131%2823%2900473-4

In this episode I talk with Case Western Reserve University Professor Andrew Pieper about how it might be possible to restore neuroplasticity and cognition in Alzheimer's disease. The conversation focuses on a recently published study from his laboratory which shows that a chemical called P7C3-A20 that restores energy balance in brain cells can reverse brain pathology and restore cognitive functio...

In this lecture I describe how changes occurring in the brain during normal aging set contribute to the pathogenesis of Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, and frontotemporal dementia.   Cellular and molecular hallmarks of aging predispose brain cells to neurodegenerative orders with environmental and genetic factors determining if and when the disease manifest...

During the past decade several new technological advances have enabled the identification of ensembles of neurons that encode a specific memory trace (engram cells) and for controlling the activity of engram cells so that recall or inhibition of a memory is controlled by the experimenter. The technologies include fluorescence 'tagging' of engram cells and optogenetic activation or inhibition of th...

Recent discoveries show that some neurodegenerative disorders occur because of abnormalities in the processing of RNA in the cell nucleus and/or its export from the nucleus. Johns Hopkins University Associate Professor Shuying Sun is at the forefront of research that is establishing the molecular mechanisms responsible for RNA dysregulation in amyotrophic lateral sclerosis (ALS) and frontotemporal...

NOTE: This lecture with slides presented can be found on the Brain Ponderings YouTube Channel. This episode begins by highlighting recent evidence showing adverse effects on the brain of excessive activation of the mTOR pathway as a consequence of dietary branched chain amino acid consumption. Then I describe evidence that Beyond the age of 40 years brain aging results in progressive decrements in...