Serotonin Harnesses Small RNAs To Strengthen Synapses

Nobel Laureate Eric R. Kandel and colleagues have discovered a new role for neurotransmitters: They can regulate microRNAs, which generally inhibit protein synthesis (Neuron 2009, 63, 803). The findings clarify how synapses are strengthened and could shed light on the formation of lasting memories, which depends on protein synthesis. Kandel, a Columbia University neuroscientist; Thomas Tuschl, a molecular biologist at Rockefeller University; and coworkers made the observations in the sea snail Aplysia californica, which is often used as a model organism in neuroscience because of its large neurons. The researchers determined that serotonin, a neurotransmitter released during learning, reduces levels of several microRNAs found in the sea snail’s brain. Depletion of miR-124, the most abundant of the microRNAs, unleashes production of the transcription factor known as CREB (cAMP response element binding protein) and the subsequent biochemical chain of events that strengthens existing synapses and creates new synapses. This pathway is responsible for the formation of long-term memory. The researchers believe that the same microRNA regulatory process will be found in mammals.