Inhibitory GABAergic neurons in the cerebral cortex have been thought to only have short axons that form synapses on excitatory glutamatergic neurons in local circuits. In this episode I talk with Heidelberg University Professor about her stellar career punctuated by major discoveries concerning mechanisms of excitatory and inhibitory neurotransmission in the cerebral cortex. The conversation focuses on her recent discovery of inhibitory neurons with long axons that synapse upon excitatory or inhibitory neurons in different regions of the cerebral cortex. These long distance inhibitory pathways function to synchronize neural network activities of different brain regions and may also play important roles in learning and memory and task execution. Dysfunction of GABAergic interneurons is increasingly recognized to occur early in Alzheimer's disease and other neurological disorders with important implications for the development of novel treatments.

LINKS

Monyer laboratory: https://www.dkfz.de/en/clinical-neurobiology

Review article on cortical inhibitory projection neurons:

file:///Users/markmattson/Downloads/s41583-020-0344-9.pdf

Relevant original research articles:

https://pmc.ncbi.nlm.nih.gov/articles/PMC11233578/pdf/41467_2024_Article_50055.pdf

https://www.cell.com/neuron/fulltext/S0896-6273(15)01035-1?_returnURL=https%3A%2F%2Flinkinghub.elsevier.com%2Fretrieve%2Fpii%2FS0896627315010351%3Fshowall%3Dtrue

https://www.cell.com/cell-reports/fulltext/S2211-1247(21)00115-7?_returnURL=https%3A%2F%2Flinkinghub.elsevier.com%2Fretrieve%2Fpii%2FS2211124721001157%3Fshowall%3Dtrue

The interactions between the immune and nervous systems in chronic pain are complex and occur at multiple points in the pain pathways from the sernsory neurons to the spinal cord and into the brain. In this episode I talk with University of Texas MD Anderson Cancer Center Neuroimmunologist Peter Grace about his research career and his discoveries concerning the roles of glial cells and lymphocytes in chronic pain. In chronic pain B lymphocytes produce antibodies against normal proteins. These autoreactive antibodies drive pain by acting on receptors on neurons and glial cells. Blocking the interaction between the autoantibodies and neural cells can alleviate pain in animal models thus revealing a new target for drug development.

LINKS

Grace laboratory:

https://www.mdanderson.org/research/departments-labs-institutes/labs/grace-laboratory.html

Related publications:

https://pmc.ncbi.nlm.nih.gov/articles/PMC8108590/pdf/painreports-6-e905.pdf

https://pmc.ncbi.nlm.nih.gov/articles/PMC11479571/pdf/nihms-2025884.pdf

https://pmc.ncbi.nlm.nih.gov/articles/PMC11903150/pdf/nihms-2053971.pdf

https://pmc.ncbi.nlm.nih.gov/articles/PMC12445798/pdf/nihms-2111181.pdf

Harvard University Professor Paola Arlotta has made major contributions to understanding how the diversity of cell types in the brain are established during development. Her lab identified molecular programs that shape cell-identity acquisition and reprogramming from on type to another. Her recent research on human brain organoids has demonstrated remarkable conservation of the timing and organization of the cellular architecture of the human brain. Recently her team showed that human brain organoids record the passage of time over many years. In this episode I talk with Paola about her career with a focus on her fascinating research on human brain organoids which is elucidating unique features of the human brain, is providing new insight into mechanisms of human brain disorders and potential novel treatments.

LINKS
Arlotta Laboratory:

https://www.hsci.harvard.edu/people/paola-arlotta-phd

Review article:

https://www.annualreviews.org/docserver/fulltext/genom/26/1/annurev-genom-111522-014009.pdf?expires=1793025978&id=id&accname=guest&checksum=011AEC12CD15297D1293F3CD3F4D26A2

Human brain organoid original research articles:

https://pmc.ncbi.nlm.nih.gov/articles/PMC13581598/pdf/41586_2026_Article_10877.pdf

https://pmc.ncbi.nlm.nih.gov/articles/PMC11338177/pdf/nihms-2010600.pdf

https://pmc.ncbi.nlm.nih.gov/articles/PMC9990683/pdf/nihms-1838109.pdf

University of Pennsylvania professor Amita Sehgal's laboratory has made major advances in understanding the molecular mechanisms that control circadian clocks and their roles in a range of fundamental biological processes including energy metabolism and sleep. In this episode Amita describes her discoveries with a focus on how cell rhythms drive behavior, brain health, and disease susceptibility throughout life.

LINKS

Sehgal laboratory: https://www.med.upenn.edu/sehgallab/

Review article:

https://pmc.ncbi.nlm.nih.gov/articles/PMC9197224/pdf/nihms-1814239.pdf

Original research articles mentioned in this podcast:

https://pmc.ncbi.nlm.nih.gov/articles/PMC12999507/pdf/41586_2025_Article_10050.pdf

https://pmc.ncbi.nlm.nih.gov/articles/PMC12337293/pdf/pnas.202427085.pdf

https://pmc.ncbi.nlm.nih.gov/articles/PMC11530234/pdf/elife-88322.pdf

This year the Nobel Prize in physiology or medicine was awarded to three scientists for optogenetics – a method for activating or inhibiting neurons with light. In this episode I talk with UC Berkeley scientist Miriam Morales about magnetogenetic technologies being developed to enable activation or inhibition of specific neurons in the brain with magnetic fields as a means of understanding how the brain works and restoring normal function in individuals with neurological disorders. Her research focuses on understanding how neuronal activity causally contributes to behavior. To address this question, she has developed approaches to remotely activate ion channels and control cellular activity. Her goal is to determine how the coordinated activity of neurons and glial cells shapes brain function.

LINKS

Hernandez Morales webpage:

https://miriamhmorales.com/

Magnetogenetics review article:

https://www-jneurosci-org.proxy1.library.jhu.edu/content/46/31/e0315252026

Original research articles

https://pmc.ncbi.nlm.nih.gov/articles/PMC8479696/pdf/main.pdf

https://pmc.ncbi.nlm.nih.gov/articles/PMC7204511/pdf/nihms-1574792.pdf

https://pmc.ncbi.nlm.nih.gov/articles/PMC13174281/

Growth hormone (GH) is produced by cells in the pituitary gland and released into the blood where it travels to the liver and therein stimulates the production of insulin-like growth factor 1 (IGF1). The release of GH which occurs in a pulsatile manner is controlled by neurons in the brain. The GH – IGF1 neuroendocrine system is critical for normal growth of the body during development. During his career, University of Oklahoma Professor Bill Sonntag's laboratory has established that IGF1 production declines during aging and that IGF1 acts on brain cells in ways that promote synaptic plasticity and learning and memory. In this episode I talk with Bill about IGF1's roles in neuroplasticity and brain aging, how IGF1 may affect neuronal network activity and enhance resistance of neurons to stress, and how this knowledge may applied to counteracting aging and bolstering brain function.

LINKS:

Sonntag's University of Oklahoma webpage: https://www.ouhealth.com/research-experts/william-e-sonntag-phd/

Review article on GH – IGF1 and the brain:

https://pmc.ncbi.nlm.nih.gov/articles/PMC4388761/pdf/nihms639724.pdf

Original research articles relevant to this podcast:

https://pubmed.ncbi.nlm.nih.gov/?term=sonntag+w+igf-1+brain&sort=date&size=200

Tumor necrosis factor (TNF) is a pro-inflammatory cytokine known for its detrimental effects on tissues in disease such as rheumatoid arthritis, Crohn's disease, and skin psoriasis. However, TNF has normal functions in the absence of inflammation. TNF is produced in low amounts by cells in the brain – particularly microglia and astrocytes – and neurons can respond to TNF in several ways. In this episode I talk with McGill University neuroscientist David Stellwagen about evidence that TNF plays important roles in regulating rapid synaptic adaptations to neural network activity. Such effects of TNF on synaptic plasticity may regulate adaptive changes in neural circuits and consequent changes in behaviors. We also talk about work in my lab showing that TNF can protect neurons against damage and degeneration under certain conditions.

LINKS

Stellwagen Laboratory: https://www.stellwagenlab.org/

Review article: https://www.nature.com/articles/s41380-026-03861-4

Original research articles:

https://www.nature.com/articles/nature04671

https://pmc.ncbi.nlm.nih.gov/articles/PMC9734040/pdf/41380_2022_Article_1737.pdf

https://pmc.ncbi.nlm.nih.gov/articles/PMC10993029/pdf/jneuro-44-e2278222024.pdf

https://pmc.ncbi.nlm.nih.gov/articles/PMC40978/pdf/pnas01498-0326.pdf

https://www.nature.com/articles/nm0796-788

https://onlinelibrary-wiley-com.proxy1.library.jhu.edu/doi/epdf/10.1002/%28SICI%291098-2396%28200002%2935%3A2%3C151%3A%3AAID-SYN8%3E3.0.CO%3B2-P