Glutamate uptake decreased in Alzheimer's disease
Professor Dennis Selkoe discusses the finding that amyloid beta seems to decrease the uptake of glutamate by synapses.
We are now studying the way that human a-beta [amyloid beta] doublets and triplets from an Alzheimerâ€™s [disease] patient block LTP [long-term potentiation] or enhance the phenomenon of long-term depression of synapses, which is not good. What weâ€™ve learned is that a-beta seems to decrease the uptake of glutamate by synapses, so there is too much glutamate in the extracellular space outside the synaptic terminal, and we donâ€™t know exactly how a-beta builds up glutamate on the outside, but we know that glutamate then affects NMDA receptors, which are receptors for glutamate. So, indeed, we believe that small amounts of a-beta, and itâ€™s very potent at these sub-nanomolar concentrations, interferes with proper NMDA receptor function. Now I cannot tell you that itâ€™s only NMDA receptors; other kinds of excitatory amino acid receptors like AMPA receptors and metabotropic glutamate receptors are already likely to be involved, we already have evidence for the so-called mGluR receptors. So NMDA [receptors] are very important, mGluR receptors are very important and probably before that, upstream of that, the mechanism for transporting glutamate into the cell (the glutamate transporter) is adversely impacted by a-beta oligomers.
alzheimer, glutamate, receptor, nmda, ampa, ltp, ltd, long, term, potentiation, depression, dennis, selkoe
- ID: 2141
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1101. AMPA and NMDA Receptors
Professor Graham Collingridge describes the roles played by NMDA and AMPA receptors in long-term potentiation (LTP).
2140. Cells - a-beta inhibits long-term potentiation
Professor Dennis Selkoe notes amyloid beta oligomers are very potent inhibitors of long-term potentiation (LTP) and can 'short circuit' synapses in the hippocampus.
1100. Glutamate Receptors
Professor Graham Collingridge describes the glutamate receptor, AMPA, the workhorse receptor for communicating information.
811. The Glutamate System
Professor Trevor Robbins describes some of the key functions of the excitatory glutamate system, which is integral to information processing and long-term potentiation.
1109. NMDA Receptors, Multi-protein Complexes, & LTP
Professor Tom O'Dell describes the role played by NMDA receptors, as part of a large multi-protein complex, in facilitating long-term potentiation (LTP).
Professor Tom O'Dell defines depotentiation - the erasure of long-term potentiation (LTP) at the synapse.
1099. Long-term Depression
Professor Graham Collingridge describes the process of long-term depression (LTD), a way of decreasing the efficiency of synaptic transmission.
1997. Learning and memory
Learning and memory are two intimately linked cognitive processes that stem from interactions with the environment (experience).
2082. Depressed learning
Professor Wayne Drevets discusses specific types of learning deficits associated with depression. These may be caused by biochemical impairments in long-term potentiation.
1277. Molecules for Memory
Communication in brain cells is guided by interactions between genes and biochemicals at the synapse. These interactions can lead to the formation of new synapses.