A family of photoswitchable NMDA receptors

Within the nervous system, neurons are organized into extensive networks via connections called synapses. To signal across a synapse, one neuron releases chemical messengers that bind to “receptors” on the surface of the neighboring cell. The ease with which neurons can communicate can change depending on how often a synapse is used. This adaptability is known as synaptic plasticity, and is central to the formation of memories. NMDA receptors are one group of receptors that play an important role in synaptic plasticity. There are several types of NMDA receptor, which are made up of different combinations of protein subunits and have different properties. This means that each type contributes to synaptic plasticity in a slightly different way. Other receptors found in neurons have been studied using a technique called chemical optogenetics, which allows the activity of modified proteins to be turned on and off by light. Now, Berlin, Szobota et al. have designed a toolbox that enables the activity of four of the NMDA receptor subunits to be controlled with light, which activates or blocks the NMDA receptors that they form (which includes several of the main receptor types). Thus, how these types of NMDA receptor contribute to synaptic plasticity can be investigated. The toolbox can be used to control synaptic plasticity under a wide range of conditions. Plasticity can be induced or prevented in either single synaptic connections or large regions containing many thousands of synapses. The approach works in individual neurons grown artificially in the laboratory, in brain slices and in the living brain. Furthermore, synaptic plasticity can be controlled precisely to affect single synaptic events (which occur in milliseconds) or it can be controlled over several days to study whether this affects how neurons develop. The next steps will be to expand the toolset so that the activity of all the NMDA receptor subtypes can be controlled using light. Further studies could then incorporate the receptors into the brains of mammals to study how the receptors’ activity affects a range of processes including memory formation and disease.