The development of an iontronic pipette at Linköping University has opened up new avenues for neurological research. This innovative tool allows researchers to deliver ions directly to individual neurons without affecting the surrounding extracellular milieu. By controlling the concentration of various ions, scientists can gain valuable insights into how brain cells respond to different stimuli and interact with each other.

The human brain consists of approximately 85-100 billion neurons, supported by a similar number of glial cells that provide essential functions such as nutrition, oxygenation, and healing. The extracellular milieu, a fluid-filled space between the cells, plays a crucial role in maintaining cell function. Changes in ion concentration within this environment can activate or inhibit neuronal activity, making it essential to study how local changes affect individual brain cells.

Previous attempts to manipulate the extracellular environment involved pumping liquid into the area, disrupting the delicate biochemical balance and making it difficult to determine whether the substances themselves or the changed pressure were responsible for the observed effects. To overcome this challenge, researchers at the Laboratory of Organic Electronics developed an iontronic micropipette measuring only 2 micrometers in diameter.

This tiny pipette can deliver ions such as potassium and sodium directly into the extracellular milieu, allowing scientists to study how individual neurons respond to these changes. Glial cell activity is also monitored, providing a more comprehensive understanding of brain function.

Theresia Arbring Sjöström, an assistant professor at LOE, highlighted that glial cells are critical components of the brain’s chemical environment and can be precisely activated using this technology. In experiments conducted on mouse hippocampus tissue slices, it was observed that neurons responded dynamically to changes in ion concentration only after glial cell activity had saturated.

This research has significant implications for neurological disease treatment. The iontronic pipette could potentially be used to develop extremely precise treatments for conditions such as epilepsy, where brain function can be disrupted by localized imbalances in ion concentrations.

Researchers are now continuing their studies on chemical signaling in healthy and diseased brain tissue using the iontronic pipette. They also aim to adapt this technology to deliver medical drugs directly to affected areas of the brain, paving the way for more targeted treatments for neurological disorders.

The recent study conducted at Mount Sinai has shed new light on the complex circuitry involved in anxiety and depression. Researchers have discovered distinct roles for two dopamine receptors located on nerve cells within the ventral hippocampus, a region crucial for regulating emotions and stress responses. This groundbreaking finding expands our understanding of dopamine signaling beyond its well-known actions in other brain regions that influence reward and motivation.

The study’s senior author, Eric J. Nestler, MD, PhD, emphasizes the importance of the hippocampus in decision-making, particularly in anxiety-inducing situations. He notes that the newly discovered D1 and D2 expressing cells in the ventral hippocampus convey information related to decision-making under stressful conditions.

Researchers investigated the influence of dopamine signaling within the ventral hippocampus on approach/avoidance behavior in male mice. They found that D1 and D2 dopamine receptors expressed in different neuronal populations are called into play to help execute approach/avoidance decisions. These receptors and the cells that express them mediate opposite approach/avoidance responses, and are differentially impacted by dopamine transmission in that region of the brain.

The team’s unexpected behavioral observation was that mice whose D2 cells were artificially activated became much less fearful. This discovery underscores the importance of dopamine in the hippocampal circuitry and highlights the need to reconsider dopamine signaling in many brain regions associated with learning, memory, and emotional behavior.

Dr. Nestler credits his research team for their creative advances in this investigation and notes that future studies will focus on showing precisely how the dopamine-hippocampus circuit modulates approach/avoidance is dysregulated in several stress-related conditions, such as anxiety disorders and major depressive disorders (which involve increased avoidance) and in drug addiction.

By helping to delineate the neuromodulatory circuits that govern these disorders, Dr. Nestler believes that his team is taking an essential step toward addressing a leading cause of disability in humans worldwide.

This breakthrough research has significant implications for our understanding of anxiety and depression and may lead to the development of more effective treatments for these conditions.

The study of Huntington’s disease has been a longstanding mystery in neuroscience. Researchers at the University of Buffalo have made significant progress in understanding the disease by identifying two specific signaling proteins that play opposing roles in its progression.

The mutated huntingtin protein (HTT) is responsible for causing Huntington’s disease, but how it leads to the degeneration of neurons remains unclear. However, researchers have found that HTT functions as a traffic controller inside neurons, moving different cargo along axons with the help of other proteins. Reducing the amount of non-mutant HTT can lead to neurological problems.

In this study, the researchers focused on two signaling proteins: GSK3ß and ERK1. They were expressed more in the neurons of Huntington’s disease patients than in normal neurons. The team used fruit fly larvae with a mutant HTT to understand how these proteins affect neuronal function.

When they inhibited GSK3ß, they found that it led to less defects in axonal transport and reduced neuronal cell death. On the other hand, inhibiting ERK1 resulted in more axonal blockages and cell death.

The researchers suggest that ERK1 may protect neurons in the face of Huntington’s disease, while GSK3ß may exacerbate the condition. This means that therapeutics could potentially target these signaling proteins differently to treat this severe neurological disorder.

The study was supported by several organizations, including the National Institute of Neurological Disorders and Stroke, the Mark Diamond Research Fund, and the BrightFocus Foundation.

This research is a significant step towards understanding the progression of Huntington’s disease. By identifying two proteins with opposing effects, researchers can now explore ways to develop treatments that target these proteins differently. This could potentially lead to new therapies for this devastating disease.