 In most of the body's organs, like the heart, any disruption of the consistent and predictable communication that occurs between cells has devastating consequences. In the brain, however, proper functioning actually depends on constant changes in cell-to-cell communication. Without these dynamic changes, we are unable to learn, make memories, or adapt our behavior to new situations. In a recent study, scientists revealed a new signaling pathway responsible for such changes. Cells in the brain communicate mostly through specialized junctions called synapses, which are distributed along the dendrites, the tree-like branches of neurons. In many neurons, synapses frequently occur on tiny bumps, or spines, that protrude along dendrites. Changes in cell-to-cell communication cause sustained changes in the structure of these spines. For example, when brain activity causes synapses to become stronger, the spine on which they are located becomes bigger. These processes are called functional and structural long-term potentiation, or LTP. Decades of research have revealed key proteins and signaling molecules that contribute to the changes in synaptic communication that are responsible for learning and memory. However, the details of the underlying signaling mechanisms have often remained elusive. For example, the protein BDNF and its receptor, Track B, are known to be important for structural LTP, but their exact contributions were unclear. To further characterize the role of BDNF and Track B in LTP, researchers at the Moxplonk Florida Institute for Neuroscience and Duke University monitored Track B activity in the memory center of live rodent brain tissue. Stimulating a single spine by carefully releasing the excitatory neurotransmitter glutamate caused the spine to grow rapidly, as expected, and activated Track B. But inactivating BDNF outside of cells with an antibody impaired both Track B activation and spine growth. Selectively eliminating BDNF postsynaptically had a similar effect, indicating that the release of BDNF from the postsynaptic cell helped activate Track B during structural LTP, or SLTP. This result was surprising because BDNF is classically released pre-synaptically. Therefore, the researchers confirmed the presence of BDNF in dendrites and spines using electron microscopy. Was the postsynaptic BDNF responsible for the activation of Track B and induction of structural LTP released from the spine itself? To answer that question, the scientists verified that BDNF was released from spines using a fluorescent sensor molecule. Subsequent experiments showed that functional as well as structural LTP depended specifically on postsynaptic BDNF, highlighting the importance of this spinotonomous signalling system in some of the most basic mechanisms of learning and memory. Taken together, these results revealed a novel BDNF Track B signalling loop that occurs in single spines and plays a critical role in determining how the structure and strength of synapses are altered. Future studies will need to determine how this signalling pathway interacts with other signalling pathways to support learning and memory.