Individual variability in synaptic gene expression and synapse density in induced pluripotent stem cell–derived neurons predicted macro-scale alterations in gray matter volume and gamma-band activity in patients with Schizophrenia.
SIRS2026.
This genetic association study tests whether genetically driven variability in excitatory neurons’ transcriptome and synapse density in patient-derived neurons in vitro explain individual changes in cortical morphology, electrophysiology, and cognitive impairments in vivo.
Why are some people unable to hear from birth, even though their inner ear appears intact? One possible cause lies in the so-called OTOF gene. It plays a central role in transmitting sound signals from the hair cells to the auditory nerve. Without this function, acoustic information does not reach the brain.
Researchers from the German Primate Center—Leibniz Institute for Primate Research, the University Medical Center Göttingen, and the Max Planck Institute for Multidisciplinary Sciences have now, for the first time, generated marmosets in which this gene has been knocked out precisely. The animals are healthy and develop normally, but are deaf from birth. This provides the first primate model that realistically replicates key characteristics of human deafness. The results are published in Nature Communications.
Hearing loss is one of the most common congenital sensory disorders in humans. A major cause is a defect in the OTOF gene. This gene ensures that the protein otoferlin is produced in the inner ear. This protein is necessary for sound signals to travel from the hair cells to the auditory nerve. Without it, the ear still functions externally, but the signals do not reach the brain.
This debate took place in Marist College on Friday September 8th 2023. It was one of the public components of a conference on the topic of panpsychism organised by Andrei Buckareff and Philip Goff, as part of the Templeton funded project ‘Panpsychism and Pan(en)theism: Philosophy of Religion meets Philosophy of Mind.’ https://sites.google.com/view/panpsyc…
Filmed and edited by Jay Shapiro.
Tiny hair cells located in the inner ear help us hear and maintain balance. On top of each hair cell is a hair bundle, a sensory organelle that converts mechanical input from sound or movement into electrical output, which is then passed on to the brain. Previous research has shown that hair bundles aren’t simply passive entities. They actively oscillate to amplify weak audio signals or to tune into specific frequencies. Biologists have also observed bundles oscillating in the absence of stimuli. Models have tried to capture this bundle behavior, but the connection between active oscillation and the audio response has not been made clear. A new thermodynamic model of energy flow within hair bundles suggests that they work like tiny machines [1]. Depending on the stimulus, the bundles either extract power from incoming sound waves or inject power into them—corresponding, respectively, to sensing or amplifying a stimulus.
In the inner ear, an active process called cochlear amplification helps humans (and other mammals) hear the faintest of sounds. When a faint whisper enters the ear, for example, the outer rows of hair cells respond to the weak signal by moving in a way that amplifies the sound waves for the inner hair cells, which are the ones that send a message to the brain. Molecular motors propel the movement or twisting of hair bundles required for these functions.
Previous work has explored how much energy a hair cell consumes to drive bundle oscillations, but the resulting models have typically assumed that bundles are moving spontaneously—that is, in the absence of external stimuli. Roman Belousov from the European Molecular Biology Laboratory in Germany and his colleagues have developed a stochastic thermodynamic model that includes an energy input from sound waves. “Instead of just looking at how a hair bundle moves on its own, we wanted to add what happens when it interacts with sound,” Belousov says.
The brain? It has a flexible social perception. In interactions with people from different ethnic groups, it tends to respond more inclusively when a shared national identity is made salient. A study, by the University of Trento, Italy, and Nanyang Technological University, Singapore (NTU Singapore), published in Proceedings of the National Academy of Sciences, sheds light on the underlying neural mechanisms.
The findings help to better understand the relationship between ethnic and national identity and have implications for improving intergroup relations in multicultural societies.
The study shows that the brain’s representation of social boundaries can rapidly reorganize in response to context. The research team suggests that this neural flexibility underlies the human ability to navigate complex social environments characterized by multiple and interconnected group identities.
That hasn’t stopped some from exploring the idea as part of a secretive effort to realize an alternative to anti-aging tech that sounds like it was ripped straight out of a dystopian science fiction novel. A billionaire-backed stealth startup, called R3 Bio, recently announced that it was raising money to develop non-sentient monkey “organ sacks,” as Wired reported last week, an eyebrow-raising alternative to animal testing. Such structures would contain all typical organs excluding the brain, ultimately serving as a source for donor organs and tissues.
But according to a sprawling followup investigation by MIT Technology Review, R3 Bio’s founders secretly have a far more ambitious goal in mind: creating entire “brainless clones” of the human body that aging or ill individuals could one day transplant their brain into. One advantage of not developing the brain in the donor bodies, albeit a ghoulish one: such a brain-free clone would neatly circumvent certain moral conundrums over the concept.
Still, to call the idea ethically fraught would be a vast understatement. Despite an insider likening a pitch they heard from R3’s founder, John Schloendorn, to a “close encounter of the third kind” with “Dr. Strangelove” in an interview with Tech Review, the company has since distanced itself from the idea of brainless human clones.
New in eNeuro from Periandri et al: Systematically comparing brain markers affected by brief versus long-term exposure to alcohol in mice unveils shared and different mechanisms that may inform alcohol use disorder treatment development.
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Epigenetic and transcriptional mechanisms are key contributors to alcohol use disorder (AUD). However, a better understanding of the specific genes, transcripts, and chromatin marks affected is necessary to inform novel pharmacotherapies. Here, we systematically investigate the genome-wide epigenetic and transcriptomic effects of ethanol across key brain regions relevant to AUD and assess how these outcomes differ between acute and chronic exposure in male C57BL/6J mice. We show that alcohol-derived acetate contributes to histone acetylation in the brain in response to acute or chronic exposure, with a broader and more robust effect following repeated exposure. Further, we find that chromatin and transcriptomic changes elicited by acute or chronic ethanol exposure are predominantly specific to brain region, and observe more robust dysregulation of gene and transcript expression following acute exposure. We show that ethanol-induced transcriptional changes are paradigm-dependent in some brain regions, most strikingly in the ventral hippocampus. Overall, our results systematically illuminate and compare key epigenetic and transcriptomic outcomes linked to acute and chronic ethanol exposure, which will guide the development of future therapeutic interventions.
Significance Statement This is the first study to systematically investigate epigenetic and transcriptomic changes following acute or chronic exposure to alcohol, focusing on key regions previously linked to substance use disorders. We show the molecular impact of alcohol varies among brain regions and in part depends on the extent of alcohol exposure. Our results provide unprecedented detail on how alcohol affects transcriptional regulation in the brain, which in turn will inform the development of needed novel therapeutic interventions for alcohol use disorder.