Toggle light / dark theme

Scientists unravel neural networks that guide guilt and shame-driven behaviors

Feelings of guilt and shame can lead us to behave in a variety of different ways, including trying to make amends or save face, cooperating more with others or avoiding people altogether. Now, researchers have shed light on how the two emotions emerge from cognitive processes and in turn guide how we respond to them.

Their study is published in eLife. The editors say it provides compelling behavioral, computational and neural evidence to explain the cognitive link between emotions and compensatory actions. They add that the findings have broad theoretical and practical implications across a range of disciplines concerned with human behavior, including psychology, neuroscience, public policy and psychiatry.

Hidden cellular layers in the brain’s memory center

Using a powerful RNA labeling method called RNAscope with high-resolution microscopy imaging, the team captured clear snapshots of single-molecule gene expression to identify CA1 cell types inside mouse brain tissue. Within 58.065 CA1 pyramidal cells, they visualized more than 330,000 RNA molecules—the genetic messages that show when and where genes are turned on. By tracing these activity patterns, the researchers created a detailed map showing the borders between different types of nerve cells across the CA1 region of the hippocampus.

The results showed that the CA1 region consists of four continuous layers of nerve cells, each marked by a distinct set of active genes. In 3D, these layers form sheets that vary slightly in thickness and structure along the length of the hippocampus. This clear, layered pattern helps make sense of earlier studies that saw the region as a more gradual mix or mosaic of cell types.

“When we visualized gene RNA patterns at single-cell resolution, we could see clear stripes, like geological layers in rock, each representing a distinct neuron type,” said a co–first author of the paper. “It’s like lifting a veil on the brain’s internal architecture. These hidden layers may explain differences in how hippocampal circuits support learning and memory.”

The hippocampus is among the first regions affected in Alzheimer’s disease and is also implicated in epilepsy, depression, and other neurological conditions. By revealing the CA1’s layered structure, the study provides a roadmap to investigate which specific neuron types are most vulnerable in these disorders.

The new CA1 cell-type atlas, built using data from the Hippocampus Gene Expression Atlas (HGEA), is freely available to the global research community. The dataset includes interactive 3D visualizations accessible through the Schol-AR augmented-reality app, which allows scientists to explore hippocampal layers in unprecedented detail.


Researchers have identified a previously unknown pattern of organization in one of the brain’s most important areas for learning and memory. The study, published in Nature Communications, reveals that the CA1 region of a mouse’s hippocampus, a structure vital for memory formation, spatial navigation, and emotions, has four distinct layers of specialized cell types. This discovery changes our understanding of how information is processed in the brain and could explain why certain cells are more vulnerable in diseases like Alzheimer’s and epilepsy.

Anil Seth — What is Consciousness: Data or Information?

Sign up for a free Closer To Truth membership to receive exclusives like early access to new episodes: https://closertotruth.com/register/

To study consciousness comprehensively and rigorously, what kinds of data or information are relevant? Data/information for Materialism theories, which are subject to the scientific method, can be well defined. But what about non-Materialism theories?

This holiday, make a tax-deductible donation of any amount to help Closer To Truth continue making content like this: https://shorturl.at/OnyRq.

Anil Seth is Professor of Cognitive and Computational Neuroscience at the University of Sussex, where he is also Director of the Sussex Centre for Consciousness Science. Seth is also Co-Director of the Canadian Institute for Advanced Research (CIFAR) Program on Brain, Mind, and Consciousness. Seth’s mission is to advance the science of consciousness, and to use its insights for the benefit of society, technology, and medicine.

Closer To Truth, hosted by Robert Lawrence Kuhn and directed by Peter Getzels, presents the world’s greatest thinkers exploring humanity’s deepest questions. Discover fundamental issues of existence. Engage new and diverse ways of thinking. Appreciate intense debates. Share your own opinions. Seek your own answers.

Wooden Neurons: An Artistic Vision of the Brain

For Louis-Jan Pilaz, days spent with tools and wood began as simple home improvement projects. He soon found himself learning how to whittle scraps of wood. Then, as a neurobiologist, Pilaz noticed a striking parallel. “It made so much sense to use wood to render neurons…They look like trees, and they have this flow of energy that is just like in neurons.” Inspired, he began to shape wood into intricate neural forms, transforming casual whittling into science-inspired woodworking art.

When he first shared his artwork on X (then Twitter), the response was positive, and people expressed their interest in his work. Encouraged by his graduate student, Pilaz opened an Etsy shop in 2021 to sell his wood sculptures, and NeuroWoodworks was born.

Pilaz’s group at Sanford Research studies the development and dysfunction of the cerebral cortex and makes extensive use of microscopy, which fuels his research and serves as a source of inspiration for his wood art. “I’ve been obsessed with cell morphology since my PhD,” Pilaz said. “I experimented, just like I do in the lab, with the tools I have and tried to make [different cell] shapes.” He uses different types of wood, such as walnut and padauk, to create a variety of cell types and structures from Purkinje cells and radial glia to mitochondria.

ATP release deficiency through astrocytic connexin 43 in the dorsal hippocampus promotes depressive- and anxiety-like behaviors

New in JNeurosci from Wang et al: Impaired ATP release in the dorsal hippocampus of male mice may lead to depressive-and anxiety-like behavior. Connexin 43 may be a key molecular player in this mechanism.

▶️


Depression is a common psychiatric disorder, and increasing evidence implicates the dysregulation of extracellular ATP and hippocampal dysfunction in its pathophysiology. However, whether ATP release is involved in depression and mechanisms underlying this involvement remain unclear. Moreover, the basis for the comorbidity of depression and anxiety disorders remains unclear. In our study, we observed reduced connexin 43 (Cx43) and extracellular ATP levels in the dorsal hippocampus but not ventral hippocampus of susceptible adult male mice exposed to chronic social defeat stress. Conditional knockout of astrocytic Cx43 or its specific knockdown in dorsal hippocampal astrocytes led to depressive-and anxiety-like behaviors, whereas neuronal knockout of Cx43 had no effect on these behaviors. These deficits were accompanied by decreased extracellular ATP levels, while supplementation with exogenous ATPγS reversed these behavioral deficits. We further identified Cx43 as a critical regulator of ATP release and a modulator of astrocytic network connectivity and morphology. Notably, overexpression of Cx43 combined with the inhibition of ATP-degrading enzymes in the dorsal hippocampus restored ATP levels and ameliorated behavioral deficits. Taken together, our results demonstrate that deficiency of ATP release from dorsal hippocampal astrocytes leads to depressive-and anxiety-like behaviors, primarily through Cx43. These findings shed new light on the mechanisms by which ATP regulates depression and anxiety pathogenesis and the role of dorsal hippocampus in depression and anxiety, providing potential therapeutic targets for treating these comorbid disorders.

Significance statement This study provides the first direct evidence of a causal relationship between astrocytic Cx43 in the dorsal hippocampus and depressive-like behaviors. It highlights the crucial role of ATP release in the comorbidity of depression and anxiety. Astrocyte-specific knockout or knockdown of Cx43 in the dorsal hippocampus resulted in reduced extracellular ATP levels and emotional disturbances. Conversely, restoring Cx43 expression combined with inhibition of ATP degradation rescued both ATP levels and behavioral deficits in susceptible mice. These findings underscore the central role of astrocytic Cx43-mediated ATP release in the pathophysiology of depression and highlight promising therapeutic strategies for the treatment of comorbid depression and anxiety.

TNF-α signaling mediates the dopaminergic effects of methamphetamine by stimulating dopamine transporters and L-type Ca2+ channels

An inflammatory cytokine in the brain can drive the addictive properties of methamphetamine by triggering the release of dopamine, according to new preclinical work in Science Signaling.


Dopamine release that underlies methamphetamine addiction is driven by the cytokine TNF-α

Microgel-based antioxidant system advances biohybrid brain research

Researchers have unveiled a breakthrough technology that could transform the way scientists build and study lab-grown brain tissue models. The innovation, called Cellular RedOx Spreading Shield (CROSS), delivers long-lasting antioxidant protection to stem cells, enabling the reliable production of high-quality extracellular vesicles (EVs) that strengthen neuron-glia networks.

The study, published in the journal Advanced Functional Materials, was led by University of Illinois Urbana-Champaign chemical and biomolecular engineering professor Hyunjoon Kong and chemistry professor Hee Sun Han, and performed by Ryan Miller, currently a post-doctoral fellow at Georgia Tech.

Jonghwi Lee, in the chemical engineering department at Chung-Ang University in South Korea, and Young Jun Kim at the Korean Institute of Science and Technology–Europe, collaborated on the project.

/* */