Inhibition enhances spatially-specific calcium encoding of synaptic input patterns in a biologically constrained model

摘要

How do we form new memories? The human brain contains almost 90 billion neurons, which communicate with one another at junctions called synapses. Each neuron has a shape a little like that of a tree, and is covered in branches called dendrites. Synapses typically form between the end of one neuron and a dendrite on another. Most scientists believe that the brain forms new memories by changing the strength of these synapses. But a number of questions remain about how this process works. There are two types of synapses excitatory and inhibitory. When an excitatory synapse becomes active, calcium ions flow into the dendrite of the receiving neuron. The calcium ions then trigger processes inside the cell that are essential for changing the strength of the synapse, and thus forming a memory. But what happens when an inhibitory synapse becomes active? How does this affect memory? Additionally, each neuron forms synapses with thousands of others, with several synapses on a single dendrite. To form a memory about a specific experience, the brain must strengthen only the synapses that relate to that experience. How does the brain manage to target these synapses specifically? Do the synapses need to be clustered on the same dendritic branch, or can they be spread apart? And do all the synapses need to be active at exactly the same time? Dorman et al. investigated these questions by developing a computer model of a neuron. Testing the model revealed that the synapses related to an experience do not all need to be active at exactly the same time to form a memory. Moreover, the synapses can be spread across multiple dendrites. Finally, the model showed that inhibitory synapses are critical for preventing calcium ions from spreading within dendritic branches and entering inactive synapses. This ensures that only the synapses active during a specific experience become stronger. Many brain disorders, including substance abuse and addiction, involve errors in the processes that underlie learning and memory. By increasing our understanding of how the structure of brain cells supports these processes, the current findings could one day lead to better treatments for these and other disorders.