by Fear and addiction are powerful forces that influence our actions and behaviors. The complex neuronal circuits in our brains that drive these processes make managing them a challenging task. To intervene when these processes malfunction, it is crucial to understand the underlying molecular mechanisms. Scientists at the Institute of Science and Technology Austria (ISTA) have pioneered a novel technique called Flash and Freeze-fracture that provides valuable insights into the medial habenula, a specific brain region involved in fear and stress responses. The results of their research were recently published in the journal PNAS.
When a bird encounters a predator like a fox while looking for food, it manages to escape just in time. However, the memory of this encounter lingers, and the bird associates fear and stress with the predator. Whenever it encounters a fox again, the fear memory is revived, leading to heightened attention, increased heart rate, and changes in behavior to reduce the risk of predation. This associative memory is mediated by a brain region called the medial habenula, which plays a critical role in emotional processing.
Dr. Peter Koppensteiner and his colleagues at the ISTA investigated the communication between neurons in the medial habenula to better understand how they transmit signals to each other. The results of their study challenge the general understanding of neuron communication. Typically, when a specific molecule known as the GABAB-receptor is activated on the surface of neurons, communication between them is shut down. However, in the neurons of the medial habenula, the opposite occurs. Activation of the GABAB-receptor actually elevates communication, making it the strongest synaptic facilitation in the entire brain. The underlying mechanism behind this phenomenon had remained unknown.
Driven by curiosity, the ISTA scientists set out to unravel this puzzle. Their goal was to examine the medial habenula neurons in mice after they had been activated with a light flash. However, traditional electron microscope methods lacked the necessary temporal resolution to capture the rapid processes occurring inside neurons, which take place in milliseconds. Leveraging the Flash and Freeze technique developed by Dr. Peter Jonas’ research group at ISTA, the scientists were able to freeze the neurons after light stimulation and analyze their structure. They took this method to the next level with their novel Flash and Freeze-fracture technique, which allowed them to also visualize proteins and molecules.
This advancement was critical in tracking the trajectories of proteins after neuronal activation and understanding why they occupy specific positions. The localization of certain proteins plays a crucial role in synaptic communication. The researchers discovered that rapid position changes of certain proteins strengthened the synapses. In particular, two proteins, SPO and CAPS2, which were previously unknown to have these functions, were found to localize near the synapse. CAPS2 was observed to anchor vesicles, tiny bubbles carrying neurotransmitters, to the synapse, enabling a strong release of messenger signals to the next nerve cell. This facilitated communication between nerve cells.
Understanding these details could potentially pave the way for new approaches to strengthen synapses in neurodegenerative diseases where synaptic function is impaired. Dr. Shigemoto, one of the researchers involved in the study, expressed his excitement about the publication, stating that it elucidates the mechanism behind this peculiar phenomenon in the brain.
In summary, the Flash and Freeze-fracture technique developed by scientists at ISTA has provided unprecedented insights into the communication between neurons in the medial habenula. By visualizing proteins and molecules, the researchers were able to track their trajectories and understand their role in synaptic communication. This knowledge opens up possibilities for interventions in fear and stress-related disorders and neurodegenerative diseases. The study represents a significant step forward in our understanding of the intricate mechanisms underlying neuronal circuits in the brain.
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1. Source: Coherent Market Insights, Public sources, Desk research
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