The precise regulation of Ca²⁺ signals plays a crucial role in the physiological functions of neurons. Here, we investigated the rapid effect of glucocorticoids on Ca²⁺ signals in cultured hippocampal neurons from both female and male rats. In cultured hippocampal neurons, glucocorticoids inhibited the spontaneous somatic Ca²⁺ spikes generated by Kv2.1-organized Ca²⁺ microdomains. Furthermore, glucocorticoids rapidly reduced the cell surface expressions of Kv2.1 and Ca_V1.2 channels in hippocampal neurons. In HEK293 cells transfected with Kv2.1 alone, glucocorticoids significantly reduced the surface expression of Kv2.1 with little effect on K⁺ currents. In HEK293 cells transfected with Ca_V1.2 alone, glucocorticoids inhibited Ca_V1.2 currents but had no effect on the cell surface expression of Ca_V1.2. Notably, in the presence of wild-type Kv2.1, glucocorticoids caused a decrease in the surface expression of Ca_V1.2 channels in HEK293 cells. However, this effect was not observed in the presence of nonclustering Kv2.1S586A mutant channels. Live-cell imaging showed that glucocorticoids rapidly decreased Kv2.1 clusters on the plasma membrane. Correspondingly, Western blot results indicated a significant increase in the cytoplasmic level of Kv2.1, suggesting the endocytosis of Kv2.1 clusters. Glucocorticoids rapidly decreased the intracellular cAMP concentration and the phosphorylation level of PKA in hippocampal neurons. The PKA inhibitor H89 mimicked the effect of glucocorticoids on Kv2.1, while the PKA agonist forskolin abrogated the effect. In conclusion, glucocorticoids rapidly suppress Ca_V1.2-mediated Ca²⁺ signals in hippocampal neurons by promoting the endocytosis of Kv2.1 channel clusters through reducing PKA activity.

Impaired inhibitory synapse development is suggested to drive neuronal hyperactivity in autism spectrum disorders (ASD) and epilepsy. We propose a novel mechanism by which astrocytes control the development of parvalbumin (PV)-specific inhibitory synapses in the hippocampus, implicating ephrin-B/EphB signaling. Here, we utilize genetic approaches to assess functional and structural connectivity between PV and pyramidal cells (PCs) through whole-cell patch–clamp electrophysiology, optogenetics, immunohistochemical analysis, and behaviors in male and female mice. While inhibitory synapse development is adversely affected by PV-specific expression of EphB2, a strong candidate ASD risk gene, astrocytic ephrin-B1 facilitates PV->PC connectivity through a mechanism involving EphB signaling in PV boutons. In contrast, the loss of astrocytic ephrin-B1 reduces PV->PC connectivity and inhibition, resulting in increased seizure susceptibility and an ASD-like phenotype. Our findings underscore the crucial role of astrocytes in regulating inhibitory circuit development and discover a new role of EphB2 receptors in PV-specific inhibitory synapse development.

Experience- and activity-dependent transcription is a candidate mechanism to mediate development and refinement of specific cortical circuits. Here, we demonstrate that the activity-dependent transcription factor myocyte enhancer factor 2C (MEF2C) is required in both presynaptic layer (L) 4 and postsynaptic L2/3 mouse (male and female) somatosensory (S1) cortical neurons for development of this specific synaptic connection. While postsynaptic deletion of Mef2c weakens L4 synaptic inputs, it has no effect on inputs from local L2/3, contralateral S1, or the ipsilateral frontal/motor cortex. Similarly, homozygous or heterozygous deletion of Mef2c in presynaptic L4 neurons weakens L4 to L2/3 excitatory synaptic inputs by decreasing presynaptic release probability. Postsynaptic MEF2C is specifically required during an early postnatal, experience-dependent, period for L4 to L2/3 synapse function, and expression of transcriptionally active MEF2C (MEF2C-VP16) rescues weak L4 to L2/3 synaptic strength in sensory-deprived mice. Together, these results suggest that experience- and/or activity-dependent transcriptional activation of MEF2C promotes development of L4 to L2/3 synapses. Additionally, MEF2C regulates the expression of many pre- and postsynaptic genes in postnatal cortical neurons. Interestingly, MEF2C was necessary for activity-dependent expression of many presynaptic genes, including those that function in transsynaptic adhesion and neurotransmitter release. This work provides mechanistic insight into the experience-dependent development of specific cortical circuits.

Seven guest collaborators bring new eyes to a Smithsonian museum founder’s collection of American art

The artists known as OSGEMEOS showcase the largest exhibition of their work in the United States at the Hirshhorn Museum and Sculpture Garden

A new study from Smithsonian scientists analyzes ant and fungus species, and uncovers the origins of their close partnership

A recent exhibition shows how soldiers sent in votes during the Civil War and World War II, as many Americans would in 2020 following the spread of the Covid-19 pandemic

From the microwave to the food processor, the book author and television personality tried many appliances and devices to figure out the best ways to use them for her audience

A new book reveals striking images from six decades of the beloved Wildlife Photographer of the Year competition

A new book from the Smithsonian’s National Museum of African American History and Culture shows the images and impacts of athletes on and off the playing field

The work of Diné artist DY Begay, now on view at the National Museum of the American Indian, blends tradition and modernity

You’ve got questions. We’ve got experts

A new exhibition co-presented by the National Portrait Gallery and the Archives of American Art explores the seminal artist’s work

The early polygraph machine was considered the most scientific way to detect deception—but that was a myth

A paleontologist at the Natural History Museum in London chronicles the age of the famous and fascinating massive reptiles

A Smithsonian curator reflects back on the artistic legend, a "Renaissance man" with 28 Grammys to his name, who died Sunday at 91 years old

Written by the former chief historian of NASA, the book examines the evolution of our cosmic understanding—from early civilizations to the present day

The work, now on view at the Smithsonian American Art Museum, tells the story of two characters on the island—the last people alive in the world

FAO and French research institutions will step up cooperation in key research areas and coordinate their actions within the global framework of FAO’s renewed strategy. Two agreements signed today cover a [...]

FAO Director-General José Graziano da Silva today praised UN Secretary-General Ban Ki Moon for his support in the fight against hunger at a meeting with FAO member countries, the Committee [...]

Tens of thousands of farmers are bringing in their first rice harvest just six months after one of the worst typhoons to ever hit the Philippines left their fields in [...]

Representatives of all countries in Latin America and the Caribbean have gathered here this week to agree on the actions needed to definitively eradicate hunger in the region before 2025. [...]

A major operation to distribute seeds and tools has been launched in the Central African Republic to support [...]

Pope Francis will add his voice to the fight against hunger and malnutrition by addressing the Second International [...]

FAO Director-General José Graziano da Silva today called on countries to put nutrition high on their national and international agendas, and to take a lead role in the upcoming Second [...]

In his address to the Joint Meeting of the Finance and Programme Committees this morning, the Director-General assured Members of the determination and commitment to delivery of the current Programme [...]

Countries today endorsed a set of wide-reaching guidelines that will boost the already vital [...]

Family farming is inextricably linked to national and global food security. Both in developing and developed countries, family farming is the leading form of agriculture in food production. Family farmers [...]

The Director-General opened the session this morning noting that FAO is on the right track, and that its sharpened focus needs to translate to concrete benefits at [...]

Prince Laurent of Belgium was today appointed FAO Special Ambassador for Forests and the Environment.

The announcement was made by FAO Director-General José Graziano da Silva at the Organization’s Committee on [...]

FAO and China have signed a two-year tripartite cooperation agreement worth about N$10.5 million (US$1.5 million) that will boost the efforts of local farmers in Namibia. The agreement, which is [...]

Santiago, Chile- The declaration of the XXI Specialized Meeting on Family Farming of MERCOSUR (REAF, in Spanish) held last week in Argentina, acknowledged the advances promoted by FAO’s Director General, [...]

The Thomson Reuters Foundation, the corporate charity of the world’s biggest news and information providers, is teaming up with the UN Food and Agriculture Organization (FAO) to improve [...]

FAO Director-General José Graziano da Silva will be away from Rome during the next few weeks. During this period he will be involved in a range of [...]

Bagdad/Rome - FAO is scaling-up critical food and agriculture assistance to highly vulnerable rural households in Iraq thanks to a generous $14.7 million grant from Saudi Arabia. The donation is [...]

The [...]

Rome/New York – Queen Letizia of Spain will join international efforts against hunger and [...]

Better management of the world's ocean resources is crucial to ensuring food global security, [...]

Policy makers should support a broad array of approaches to overhauling global food systems, [...]

Milan - European governments must help combat [...]

Rome - Governments ought to review the [...]

Between last week’s Global Dialogue on Family Farming, a visit from President Evo Morales and the 3Full Article