Study sheds light on how norepinephrine release influences the fear-memory formation

Study sheds light on how norepinephrine release influences the fear-memory formation

Researchers at RIKEN Center for Brain Science have visualized the dynamic processes involving norepinephrine that influence different types of fear-memory formation in a living mouse model. Image Credit: KateStudio/Shutterstock.com The study found that a sustained state of vigilance caused a different type of memory to form than a temporary startle did - differences that were influenced by changes in calcium signaling and the signaling molecule cAMP. About norepinephrine Norepinephrine or noradrenaline is both a hormone released into the blood from the adrenal medulla and a neurotransmitter produced by nerve cells in the brain. It works together with adrenaline to prepare the body for action, by increasing heart rate, blood pressure, and blood sugar levels (as an energy source). Studies have previously demonstrated that norepinephrine release is important for the modification of synapses – connections between nerve cells that are involved in the formation and consolidation of memories. Changes in synaptic strength are thought to influence learning and memory mechanisms. Norepinephrine is mainly produced in neurons located in a brain region called the locus coeruleus. Within these neurons, norepinephrine is transported to synaptic vesicles that carry it along axons of the noradrenergic bundle to its site of release. Emotional arousal triggers activation of the locus coeruleus and the subsequent release of norepinephrine, which induces both pre- and post-synaptic adrenergic receptors at central synapses. Astrocytes are important mediators of the synaptic changes and researchers at RIKEN’s Hajime Hirase Laboratory for Neuron-Glia Circuitry wanted to observe in real-time what happens in these cells during the learning process. What did the study involve? Focusing on noradrenergic neurons originating in the locus coeruleus, the team used a light-based technique known as optogenetics to artificially stimulate brain cells, inducing the release of norepinephrine. As reported in the journal Nature Communications , this triggered two distinct chains of molecular events, one involving calcium activity and one involving cAMP. Calcium levels in astrocytes rapidly increased, while the increase in cAMP levels was slower but more sustained. We think these fast and slow dynamics are significant because calcium elevation in astrocytes promotes synaptic plasticity, or the ability of cells to form new memory connections, while cAMP elevation mobilizes energy metabolism for memory consolidation." Hirase



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