Axonal Transport of Synaptic Component in Learning and Memory
The human brain is composed of nearly 100 billion neurons, each of them containing thousands of synapses; approximately 100 trillions of them in the entire brain. Synapses are, essentially, the contact points that allow communication between neurons and, therefore, support normal functioning of the brain, including cognition. Accurate synaptic connections and their dynamic modulation are the substrate for adaptive behavior. Hence, one of the fundamental questions in Neuroscience aims at addressing the molecular mechanisms by which synaptic components are delivered to the correct synaptic connections, within a given neuron, in order to perform accurate and adaptive behaviors.
We investigated the role of the central complex broad gene (ccb), and found that it mediates axonal transport of synaptic components. This transport system was assessed in a variety of neuronal populations, including larval motor neurons and adult neurons of the ellipsoid body. In the ellipsoid body, the CCB trafficking system also participates in axonal transport of components required for proper axonal guidance. Deficits in this transport system prevent axonal growth across the midline. Overall, this trafficking network ensures delivery of the receptor CD8, FasII and Synaptobrevin (Martin-Peña & Ferrús, 2020). Transport of other synaptic proteins like Syntaxin were not mediated by CCB, which suggests the existence of alternative transport systems.
Rab11, a Rab protein within the slow recycling endosome, was found to be part of this network mediating vesicle-based axonal transport of synaptic proteins. CCB and Rab11 co-localize in the initial segment of axons, and the amount of Rab11 in axon terminals is proportional to the level of CCB activation; the lower the CCB, the less Rab11 delivered to synapses (Martin-Peña & Ferrús, 2020).
Axonal transport is usually supported by either the microtubules or the actin network. In the case of CCB, we found exclusive interaction with actin. Polymerization of actin monomers into filaments is mediated by three protein superfamilies: Arc2/3, formin and spire. CCB interacts genetically with Spire and together ensure delivery of synaptic proteins (Martin-Peña & Ferrús, 2020).
As synapses are very dynamic and constantly modified with behavior, we suspect that the trafficking network that we described might be involved in processes of learning and memory. We are currently investigating the potential role of this transport system in memory formation, with particular interest in anesthesia resistant memory. This selective form of memory has remained enigmatic for many years, while research on other types of memory has unveiled a large number of signaling pathways required for the different phases of memory. A full understanding of this mechanism is essential for identifying the targets of neurodegenerative disorders and finding palliative treatments of these diseases.
