Elucidating the mechanisms of memory
Synaptic plasticity, the ability of the synapses to strengthen or weaken over time, involves long-lasting increase (or long-term potentiation) in signal transmission between two neurons or long-lasting decrease in synaptic strength. The number of neurotransmitter receptors located on a synapse contributes to synaptic plasticity. Two glutamate receptors, Alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) and N-methyl-D-aspartate (NMDA) receptors are related to long-term potentiation. The EU-funded project SYNAPTIC ER (Understanding mechanisms regulating endoplasmic reticulum dynamics in hippocampal synaptic plasticity) has found a connection between glutamate receptors and endoplasmic reticulum (ER). During transmission, the signal travels from an axon of one neuron to the dendrite of a second neuron, receiving an input. The surface of a dendrite has dendritic spines, or small protrusions. Interestingly, some dendritic spines contain ER. These ER-containing spines are highly dynamic but the role of ER in dendritic spines has not been studied in detail. The scientists expressed different fluorescent markers in hippocampal neuronal cultures. The markers allowed them to follow the internalisation of glutamate receptors at synapses and to visualise the ER. The imaging experiments on ER-containing and ER-lacking spines showed that there was no correlation between AMPA receptor internalisation and ER content. However the activity of the NMDA receptor was found to be responsible for changes in spine size and the associated ER dynamics. Activation of NMDA receptors promoted rapid ER expansion in growing spines. The SYNAPTIC ER project has added to the knowledge base defining the role and mechanisms regulating spine ER dynamics in synaptic physiology. The results will help define molecular targets for developing drugs to treat neurodegenerative disorders such as Alzheimer's.
