A breakthrough study published today in the Journal of Neuroscience sheds new light on how brain cells relay critical information from their extremities to their nucleus, leading to the activation of genes essential for learning and memory.
Researchers have identified a key pathway that links how neurons send signals to each other, or synaptic activity, to the expression of genes necessary for long-term changes in the brain, providing crucial insights into the molecular processes underlying memory formation.
"These findings illuminate a critical mechanism that connects local synaptic activity to the broader gene expression changes necessary for learning and memory," said Mark Dell'Acqua, professor of pharmacology at the University of Colorado Anschutz Medical Campus and senior author of the study. "This paper is mainly a basic science finding of a fundamental process of what nerve cells do. Understanding this relay system not only enhances our knowledge of brain function but could also better inform therapeutic treatments for cognitive disorders."
The nucleus where the genes that modify neuron function are controlled is a long distance away from where neurons receive input from their synapses, which are located in distant dendrites that extend like branches from the trunk of a tree. This research focuses on the cAMP-response element binding protein (CREB), a transcription factor known to regulate genes vital for dynamic changes at synapses which is essential for neuronal communication. Despite CREB's well-documented role in supporting learning and memory, the exact mechanisms leading to CREB activation during neuronal activity remain unclear.
Using advanced microscopy techniques, graduate student Katlin Zent in Dr. Dell'Acqua's research group revealed a crucial relay mechanism involving the activation of receptors and ion channels generating calcium signals that rapidly communicates from synapses in remote dendrite branches to the nucleus in the neuron cell body.
"Going forward, this research will enable us to better examine the way these pathways are utilized in different disease states," said Dell'Acqua. "We could see exactly what parts of this new mechanism are interfered with and where, giving us a better idea of how this pathway affecting learning and memory is impacted. This research highlights potential targets for interventions aimed at conditions like Alzheimer's disease and other memory-related disorders."
About the University of Colorado Anschutz Medical Campus
The University of Colorado Anschutz Medical Campus is a world-class medical destination at the forefront of transformative science, medicine, education and patient care. The campus encompasses the University of Colorado health professional schools, more than 60 centers and institutes and two nationally ranked independent hospitals - UCHealth University of Colorado Hospital and Children's Hospital Colorado – which see more than two million adult and pediatric patient visits yearly. Innovative, interconnected and highly collaborative, the CU Anschutz Medical Campus delivers life-changing treatments, patient care and professional training and conducts world-renowned research fueled by $910 million in annual research funding, including $757 million in sponsored awards and $153 million in philanthropic gifts.
