Mind & Matter

Send us a textHow brains compute and learn, blending neuroscience with AI insights.Episode Summary: Dr. Marius Pachitariu discusses how the brain computes information across scales, from single neurons to complex networks, using mice to study visual learning. He explains the differences between supervised and unsupervised learning, the brain’s high-dimensional processing, and how it compares to artificial neural networks like large language models. The conversation also covers experimental techniques, such as calcium imaging, and the role of reward prediction errors in learning.About the guest: Marius Pachitariu, PhD is a group leader at the Janelia Research Campus, leading a lab focused on neuroscience with a blend of experimental and computational approaches.Discussion Points:The brain operates at multiple scales, with single neurons acting as computational units and networks creating complex, high-dimensional computations.Pachitariu’s lab uses advanced tools like calcium imaging to record from tens of thousands of neurons simultaneously in mice.Unsupervised learning allows mice to form visual memories of environments without rewards, speeding up task learning later.Brain activity during sleep or anesthesia is highly correlated, unlike the high-dimensional, less predictable patterns during wakefulness.The brain expands sensory input dimensionality (e.g., from retina to visual cortex) to simplify complex computations, a principle also seen in artificial neural networks.Reward prediction errors, driven by dopamine, signal when expectations are violated, aiding learning by updating internal models.Large language models rely on self-supervised learning, predicting next words, but lack the forward-modeling reasoning humans excel at.Related episode:M&M 44: Consciousness, Perception, Hallucinations, Selfhood, Neuroscience, Psychedelics & "Being You" | Anil Seth*Not medical advice.Support the showAll episodes, show notes, transcripts, and more at the M&M Substack Affiliates: KetoCitra—Ketone body BHB + potassium, calcium & magnesium, formulated with kidney health in mind. Use code MIND20 for 20% off any subscription (cancel anytime) Lumen device to optimize your metabolism for weight loss or athletic performance. Code MIND for 10% off Readwise: Organize and share what you read. 60 days FREE through link SiPhox Health—Affordable at-home blood testing. Key health markers, visualized & explained. Code TRIKOMES for a 20% discount. MASA Chips—delicious tortilla chips made from organic corn & grass-fed beef tallow. No seed oils or artificial ingredients. Code MIND for 20% off For all the ways you can support my efforts

Send us a textHow dietary fats and cannabinoids shape brain function and mental well-being.Episode Summary: Dr. Steven Laviolette discusses the role of lipids, particularly endocannabinoids and fatty acids, in brain signaling and mental health, discussing how dietary omega-3 and omega-6 imbalances, prenatal THC exposure, and fatty acid binding proteins (FABPs) impact mood, anxiety, and neuroinflammation, while highlighting potential dietary interventions to mitigate these effects.About the guest: Steven Laviolette, PhD is a professor at the University of Western Ontario, holding a PhD, and his lab focuses on the brain’s cannabinoid system and its role in mental health. He investigates how cannabinoids and fatty acids influence brain development and disorders like anxiety and schizophrenia.Discussion Points:The brain uses fats like endocannabinoids (e.g., anandamide, 2-AG) not just for structure but as signaling molecules to regulate emotional and cognitive processing.Prenatal THC exposure in rodents skews the omega-3/omega-6 balance toward pro-inflammatory omega-6, leading to cognitive and mood issues in offspring, but omega-3 supplementation can mitigate these effects.Fatty acid binding proteins (FABPs), especially FABP5, shuttle endocannabinoids like anandamide to degradation sites, and inhibiting FABP5 increases anandamide levels, reducing anxiety and depression without addictive side effects.FABP5 inhibitors show promise as safer alternatives to benzodiazepines.Both THC and CBD can induce problems during early development, challenging the notion that CBD is universally safe, especially during pregnancy.Dietary interventions, like omega-3 supplementation or antioxidants (e.g., L-theanine, N-acetylcysteine), may counteract the negative psychiatric effects of cannabinoid exposure, particularly during adolescence.The North American diet, high in omega-6, contributes to neuroinflammation and mental health issues, underscoring the need for nutritional neuroscience to address these imbalances.Related episode:M&M 165: PUFAs in Brain Health & Disease, Dietary Fats, Brain Lipids, Nutrition | Richard Bazinet*Not medical advice.Support the showAll episodes, show notes, transcripts, and more at the M&M Substack Affiliates: KetoCitra—Ketone body BHB + potassium, calcium & magnesium, formulated with kidney health in mind. Use code MIND20 for 20% off any subscription (cancel anytime) Lumen device to optimize your metabolism for weight loss or athletic performance. Code MIND for 10% off Readwise: Organize and share what you read. 60 days FREE through link SiPhox Health—Affordable at-home blood testing. Key health markers, visualized & explained. Code TRIKOMES for a 20% discount. MASA Chips—delicious tortilla chips made from organic corn & grass-fed beef tallow. No seed oils or artificial ingredients. Code MIND for 20% off For all the ways you can support my efforts

Brian Kerley, a family medicine-trained hospitalist known as the 'Seed Oil Disrespecter', dives into the health impacts of seed oils. He reveals their role in chronic diseases like heart disease, linking them to oxidative stress and lipid peroxidation. The discussion touches on the evolutionary mismatch between modern diets and traditional food patterns. Kerley also highlights challenges in studying long-term effects and explores the cultural implications of dietary choices, all while advocating for better patient education on nutrition.

Dr. David Healy, a seasoned psychiatrist and pharmacologist, dives into the contentious world of SSRIs and their significant side effects, including post-SSRI sexual dysfunction and vulnerabilities to suicidality. He critiques how pharmaceutical companies manipulate clinical trials and ghostwrite research, overshadowing patient experiences. Healy emphasizes the urgent need for individualized patient care and transparency in medical practices, raising concerns about the ethical implications of SSRIs and the power dynamics in healthcare.

Andrew Chadeayne, a chemist and patent lawyer, dives into the fascinating world of psychedelics. He explains the chemistry behind psilocybin and its psychoactive counterparts, debunking myths like 'lemon tekking.' Chadeayne discusses innovative drug development aimed at enhancing therapeutic benefits while minimizing hallucinogenic effects. He also explores the booming, unregulated market for products like kratom and synthetic psilocybin sold in vape shops, raising crucial questions about safety and regulation in this evolving industry.

Dr. Michael Wheeler, an Assistant Professor of Neurology at Harvard Medical School, delves into the fascinating interplay between the immune system and the brain. He discusses how the blood-brain barrier allows immune signals to influence brain function, particularly in cases of chronic stress and depression. Wheeler explores the therapeutic potential of psychedelics like psilocybin and MDMA, highlighting their role in reducing inflammation and reshaping neuroimmune interactions. The discussion unveils insights into how these substances may offer hope for treatment-resistant mood disorders.

Nikos Koundouros, a postdoctoral fellow at Weill Cornell Medicine, joins John Blenis, a prominent pharmacology professor, to unravel how omega-6 fatty acids like linoleic acid may drive triple-negative breast cancer by activating the mTOR pathway. They discuss the critical role of the FABP5 protein, uniquely enhancing cancer cell sensitivity to these fats. The conversation reveals alarming shifts in modern diets, emphasizing the need for tailored nutrition approaches based on genetic variations and cancer subtypes to improve health outcomes.

György Buzsáki, a renowned NYU professor, explores how the hippocampus transcends mere memory and spatial navigation functions to influence action planning and abstract thought. He discusses the impact of brain rhythms, particularly sharp wave ripples, which enhance communication and affect overall bodily health like glucose regulation. Delving into the interconnectedness of memory, sleep, and neural dynamics, Buzsáki challenges existing neuroscience paradigms while illuminating the evolutionary context shaping cognitive processes.

Send us a textThe biophysics of life, exploring how light & energy shape biology, with biophysicist Dr. Nirosha Murugan.Episode Summary: Dr. Murugan discusses the role of biophysics in biology, focusing on how light, particularly biophotons emitted by cells, influences processes like wound healing, neural activity, and cancer detection; how microtubules may act as biological fiber optics, the impact of modern light environments on health; her work inducing limb regeneration in frogs using silk hydrogels and growth factors; cancer as an energetic dysfunction; potential of non-invasive photonic diagnostics; the need for new tools to study these phenomena.About the guest: Nirosha Murugan, PhD is a biophysicist and assistant professor at Wilfrid Laurier University in Waterloo, Ontario. Her lab investigates the biophysics of life.Note: Podcast episodes are fully available to paid subscribers on the M&M Substack and everyone on YouTube. Partial versions are available elsewhere. Transcript and other information on Substack.Key Conversation Points:Cells emit biophotons, ultra-weak light tied to metabolism, which may carry information for processes like immune response and neural communication.Microtubules might function as biological fiber optics, potentially guiding light within cells for signaling purposes.Red and near-infrared light can accelerate wound healing and reduce inflammation, likely by modulating mitochondrial activity.Cancer cells emit distinct photonic signatures, which could enable non-invasive diagnostics by detecting light differences from healthy tissues.Modern light environments, unlike natural sunlight, may subtly affect health by altering biological responses to electromagnetic signals.Biological systems act as metamaterials, patterning energy flow in ways that constrain and shape molecular and behavioral outcomes.Related episode:M&M 221: Regenerative Energy & the Light Inside You | Jack Kruse*Not medical advice.Support the showAll episodes, show notes, transcripts, and more at the M&M Substack Affiliates: KetoCitra—Ketone body BHB + potassium, calcium & magnesium, formulated with kidney health in mind. Use code MIND20 for 20% off any subscription (cancel anytime) Lumen device to optimize your metabolism for weight loss or athletic performance. Code MIND for 10% off Readwise: Organize and share what you read. 60 days FREE through link SiPhox Health—Affordable at-home blood testing. Key health markers, visualized & explained. Code TRIKOMES for a 20% discount. MASA Chips—delicious tortilla chips made from organic corn & grass-fed beef tallow. No seed oils or artificial ingredients. Code MIND for 20% off For all the ways you can support my efforts

Send us a textShort Summary: Dr. Alex Kwan unpacks the latest neuroscience research on how psychedelics like ketamine & psilocybin reshape the brain.About the guest: Alex Kwan, PhD, is an associate professor of biomedical engineering at Cornell University. His lab employs advanced imaging to study how psychedelics and other drugs affect the mammalian brain.Note: Podcast episodes are fully available to paid subscribers on the M&M Substack and everyone on YouTube. Partial versions are available elsewhere. Transcript and other information on Substack.Episode Summary: Dr. Alex Kwan discusses how psychedelics like ketamine and psilocybin induce rapid neuroplastic changes in the brain, particularly in the prefrontal cortex, contrasting their effects with traditional antidepressants like SSRIs, and exploring their potential for treating depression and chronic pain through structural and functional brain alterations.Key Takeaways:Ketamine & psilocybin rapidly increase dendritic spine density in the prefrontal cortex, enhancing neural connections within days, unlike SSRIs, which take weeks.These drugs show sustained neuroplastic changes in mice, lasting weeks to months after a single dose, suggesting long-term brain rewiring.Serotonin 2A receptor is critical for psilocybin’s neuroplastic effects, as precise genetic knockouts in adult mice eliminate spine growth.Unlike ketamine, psilocybin activates the insula, a brain region linked to chronic pain processing, hinting at new therapeutic potential.Both drugs induce similar gene expression patterns in areas like the prefrontal cortex and amygdala, but differ in specific regions like the insula.Related episode:M&M #30: Psilocybin, Ketamine, Neuroplasticity & Imaging the Brain | Alex Kwan*Not medical advice.Support the showAll episodes, show notes, transcripts, and more at the M&M Substack Affiliates: KetoCitra—Ketone body BHB + potassium, calcium & magnesium, formulated with kidney health in mind. Use code MIND20 for 20% off any subscription (cancel anytime) Lumen device to optimize your metabolism for weight loss or athletic performance. Code MIND for 10% off Readwise: Organize and share what you read. 60 days FREE through link SiPhox Health—Affordable at-home blood testing. Key health markers, visualized & explained. Code TRIKOMES for a 20% discount. MASA Chips—delicious tortilla chips made from organic corn & grass-fed beef tallow. No seed oils or artificial ingredients. Code MIND for 20% off For all the ways you can support my efforts