Astrocytes are known to play important roles in brain energy metabolism and the regulation of neuronal network activities. A single astrocyte has a highly elaborate and expansive morphology which enables it to interact with many thousands of neurons and synapses. Moreover, astrocytes are connected to adjacent astrocytes via gap junctions and evidence suggests that these astrocyte networks may mediate long range communications within and between brain regions. In this episode I talk with University of Montreal neuroscientist Ciaran Murphy-Royal about the rapidly expanding knowledge concerning astrocyte functions in regulating brain functions and responses to environmental conditions with a focus on stress responses. Ciaran's laboratory recently showed that astrocyte activity influences anxiety states and that selective manipulations of astrocyte activity can increase or decrease fear and anxiety. We also talk about how astrocytes may mediate chronic stress-induced memory impairment.

LINKS

Murphy-Royal laboratory:

https://www.murphyroyallab.org/

Amygdala astrocytes control anxiety states:

https://www.cell.com/neuron/fulltext/S0896-6273(26)00163-7?_returnURL=https%3A%2F%2Flinkinghub.elsevier.com%2Fretrieve%2Fpii%2FS0896627326001637%3Fshowall%3Dtrue

Male – female differences in astrocyte-mediated stress responses:

https://pmc.ncbi.nlm.nih.gov/articles/PMC12246237/pdf/41467_2025_Article_61643.pdf

Early life stress, astrocyte dysfunction, and fear generalization:

https://pmc.ncbi.nlm.nih.gov/articles/PMC11798576/pdf/elife-99988.pdf

The disease process in Alzheimer's disease involves local inflammatory processes wherein microglia are activated and produce pro-inflammatory cytokines. Accumulations of amyloid beta-peptide promote neuroinflammation by causing oxidative stress and damage to neurons and the microglia react to that damage. In this episode I talk with John Fryer about mechanisms of neuroinflammation and new immunotherapy approaches targeting amyloid in Alzheimer's disease including the use of 'nanobodies' which are small single-domain antibodies produced in camels and adapted for research and therapeutic purposes. John was previously an investigator at the Mayo Clinic and is now Director of the Center for Accelerated Nanotherapeutics in Phoenix. Note that one's risk for Alzheimer's disease is reduced by regular exercise, heart-healthy diets, and keeping intellectually and socially engaged throughout life.

LINKS

Fryer webpage at Tgen:

Articles

https://pmc.ncbi.nlm.nih.gov/articles/PMC5565413/pdf/pnas.201701137.pdf

https://pmc.ncbi.nlm.nih.gov/articles/PMC13148177/pdf/nihms-2168146.pdf

https://alz-journals.onlinelibrary.wiley.com/doi/epdf/10.1002/trc2.70269

https://pmc.ncbi.nlm.nih.gov/articles/PMC13329261/pdf/ALZ-22-e71639.pdf

https://pmc.ncbi.nlm.nih.gov/articles/PMC6122978/pdf/JEM_20180653.pdf

While it has long been known that activity in neural networks in sleep differs from activity during waking hours. EEG recordings have revealed patterns of activity oscillations associated with deep (non-REM) sleep and rapid eye movement (REM) sleep. However, it remains unclear how transitions from wake to sleep and from sleep to wake are controlled. One hypothesis is that there are sleep-inducing substances that accumulate during waking hours and then reach a certain tipping point that causes sleep. However, such a sleep substance has not been identified. Genes regulating the cellular circadian clock are implicated but operate on too slow a time scale to explain wake – sleep and wake – sleep transitions. University of Tokyo professor Hiroki Ueda has accumulated evidence for a different mechanism of sleep regulation in which calcium functions as a master regulator by virtue of its effects on phosphorylation of ion channels that regulate neuronal excitability. In this episode I talk with Hiro about his elegant experiments that use cutting-edge technologies to manipulate calcium-regulated kinases (CaMKII alpha and beta) in forebrain neurons while quantifying sleep and wakefulness by continuous monitoring of breathing patterns. Hiro also talks about the development in his laboratory of next generation single-cell genetics and whole-brain single cell imaging technologies and their broad applications in neuroscience research.

LINKS Review articles https://www.sciencedirect.com/science... https://pmc.ncbi.nlm.nih.gov/articles...

Whole brain single-cell atlas of neural activity https://www.science.org/doi/10.1126/s...

Competition between kinases and phosphatases in sleep-wake cycles https://www.nature.com/articles/s4158...