Constraining Learning by Shrinking the Vesicle Pool

Abstract:  Stromalin, a cohesin complex member, was recently identified as a novel memory suppressor gene, but the mechanisms through which it constrained learning and memory remained unknown. We recently showed that Stromalin functions as a negative regulator of synaptic vesicle pool size in Drosophila neurons. Remarkably, reducing Stromalin levels in dopamine neurons enhanced learning and specifically increased synaptic vesicle numbers without altering cell numbers, their axons, or synapses. Moreover, Stromalin knockdown during a critical developmental period was necessary for this effect, which then persists into adulthood to strengthen synaptic connections and enhance memory acquisition in adult flies. Correcting the vesicle content at the dopamine neuron axon terminals through impairing anterograde vesicle trafficking rescues the enhanced learning phenotype in Stromalin knockdown flies. This work identifies a new mechanism for memory suppression, revealing that the size of the synaptic vesicle pool is controlled genetically and independently from other aspects of neuron structure and function through Stromalin. Importantly, our unique findings provide an entrée into a new research area deciphering the molecular and developmental mechanisms that constrain synaptic vesicle numbers, as well as determining the behavioral and cognitive consequences of releasing these genetic limitations on learning and memory.