A new method enables scientists to monitor the activity of key molecules involved in the growth and remodeling of connections in the brain1. These changes form the cellular basis of learning and brain development.
Certain molecules within neurons act as switches that modulate the strength of neuronal connections, or synapses; the strength reflects the extent of communication between neurons at that synapse.
The researchers studied the influence of three small molecules — RAS, RAP1 and RAP2 — on synapse strength. They used a method that boosts the amount of each molecule at any of five locations within the cell.
They fused RAS, RAP1 or RAP2 to the genes for one of five proteins known to localize at a cell structure. They injected a virus carrying one of the possible gene constructs into the brains of rats. Each molecule has a fluorescent tag that enables researchers to track its location and amount within a cell.
The cell transports the fused products to one of five structures: the endoplasmic reticulum, lysosomes, the Golgi complex or either of two parts of the cell membrane involved in signaling. The researchers then triggered neurons to fire in thin slices taken from each rat’s brain and examined how the added protein affects cell communication.
Adding RAS to the endoplasmic reticulum and portions of the cell membrane strengthens synapses, the researchers found. This process, called long-term potentiation, is critical to memory formation. RAP2 halts neuronal communication when expressed in the cell membrane at the synapse. In the lysosome, RAP1 gradually weakens synapses, a phenomenon called long-term depression that underlies both learning and forgetting.
The method could also be used to send drugs to specific locations within neurons, or to use molecules to treat conditions such as autism. The work appeared in May in Neuron.