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Neuromodulation regulates critical functions of CNS synapses, ranging from neural circuit development to high-order cognitive processes, including learning and memory. This broad scope of action is generally mediated through alterations of the strength of synaptic transmission (i.e. synaptic plasticity). Changes in synaptic strength are widely considered to be a cellular representation of learned information. Noradrenaline is a neuromodulator that is secreted throughout the brain in response to novelty or increased arousal. Once released, noradrenaline activates metabotropic receptors, initiating intracellular signaling cascades that promote enduring changes in synaptic strength and facilitate memory storage. Here, we provide an overview of noradrenergic modulation of synaptic plasticity and memory formation within mammalian neural circuits, which has broad applicability within the neurotherapeutics community. Advances in our understanding of noradrenaline in the context of these processes may provide a foundation for refining treatment strategies for multiple brain diseases, ranging from post-traumatic stress disorder to Alzheimer's Disease.
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http://dx.doi.org/10.2174/1871524919666190719163632 | DOI Listing |
Proc Natl Acad Sci U S A
September 2025
Vanderbilt Brain Institute, Vanderbilt University, Nashville, TN 37240.
Major depressive disorder affects millions worldwide, yet current treatments require prolonged administration. In contrast, ketamine produces rapid antidepressant effects by blocking spontaneous N-Methyl-D-Aspartate (NMDA) receptor signaling, which lifts the suppression of protein synthesis and triggers homeostatic synaptic plasticity. Here, we identify a parallel signaling pathway involving metabotropic glutamate receptor 5 (mGluR5) that promotes rapid antidepressant-like effects.
View Article and Find Full Text PDFProc Natl Acad Sci U S A
September 2025
Institut de Biologie de l'Ecole Normale Supérieure, Ecole Normale Supérieure, Université Paris Sciences et Lettres, Centre National de la Recherche Scientifique, Institut National de la Santé et de la Recherche Médicale, Paris 75005, France.
Excitatory glycine receptors (eGlyRs), composed of the glycine-binding NMDA receptor subunits GluN1 and GluN3A, have recently emerged as a novel neuronal signaling modality that challenges the traditional view of glycine as an inhibitory neurotransmitter. Unlike conventional GluN1/GluN2 NMDARs, the distribution and role of eGlyRs remain poorly understood. Here, we show that eGlyRs are highly enriched in the ventral hippocampus (VH) and confer distinct properties on this brain region.
View Article and Find Full Text PDFPsychopharmacology (Berl)
September 2025
División de Neurociencias, Instituto de Fisiología Celular, Universidad Nacional Autónoma de México, Ciudad Universitaria, Mexico City, 04510, Mexico.
Rationale: One of the earliest changes associated with Alzheimer's disease (AD) is the loss of catecholaminergic terminals in the cortex and hippocampus originating from the Locus Coeruleus (LC). This decline leads to reduced catecholaminergic neurotransmitters in the hippocampus, affecting synaptic plasticity and spatial memory. However, it is unclear whether restoring catecholaminergic transmission in the terminals from the LC may alleviate the spatial memory deficits associated with AD.
View Article and Find Full Text PDFMol Biol Rep
September 2025
Chitkara College of Pharmacy, Chitkara University, Rajpura, 140401, Punjab, India.
Neuroinflammation, a vital protective response for tissue homeostasis, becomes a detrimental force when chronic and dysregulated, driving neurological disorders like Alzheimer's, Parkinson's, and Huntington's diseases. Potassium (K) channels maintain membrane potential and cellular excitability in neurons and glia within the intricate CNS signaling network. Neuronal injury or inflammation can disrupt K channel activity, leading to hyperexcitability and chronic pain.
View Article and Find Full Text PDFNeurol Res
September 2025
Electrophysiology Research Center, Neuroscience Institute, Tehran University of Medical Sciences, Tehran, Iran.
Objectives: This study aimed to investigate the effects of repeated exposure to sevoflurane as an anesthetic agent during various developmental stages, namely neonatal, preadolescent, and adult, on behavioral, synaptic, and neuronal plasticity in male and female Wistar rats.
Methods: Rats were exposed to sevoflurane during three developmental stages: neonatal (PN7), pre-adolescence (PN28), and adulthood (PN90). Behavioral performance was evaluated with the Morris Water Maze.