4.8 Article

Slow AMPA receptors in hippocampal principal cells

Journal

CELL REPORTS
Volume 36, Issue 5, Pages -

Publisher

CELL PRESS
DOI: 10.1016/j.celrep.2021.109496

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Funding

  1. EMBO Long Term Fellowship [ALTF 873-2018]
  2. NeuroCure Female Fellowship [EXC-257]
  3. Deutsche Forschungsgemeinschaft (DFG) Heisenberg Professorship [PL619/3-1]
  4. DFG RU2518 DynIon (P3) [PL619/5-1]
  5. DFG under Germany's Excellence Strategy [EXC-2049-390688087-NeuroCure]
  6. ERC [647895]
  7. European Research Council (ERC) [647895] Funding Source: European Research Council (ERC)

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The study shows that in addition to the previously known fast-acting AMPA receptors, slow AMPA receptors with prolonged activity are also expressed in the hippocampal CA1 region. These slow AMPA receptors may play a significant role in synaptic transmission, short-term potentiation, and triggering of action potentials.
Glutamate receptor ion channels, including alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors, mediate fast excitatory neurotransmission in the CNS. Previous work suggested thatAMPA receptors produce a synaptic current with a millisecond duration. However, we find that about two-thirds of principal cells in the hippocampal CA1 region also express AMPA receptors with reduced desensitization that can stay active for half a second after repetitive stimuli. These slow AMPA receptors are expressed at about half of the synapses, with a flat spatial distribution. The increased charge transfer from slow AMPA receptors allows short-term potentiation from a postsynaptic locus and reliable triggering of action potentials. Biophysical and pharmacological observations imply slow AMPA receptors incorporate auxiliary proteins, and their activation lengthens miniature synaptic currents. These data indicate that AMPA receptors are a major source of synaptic diversity. Synapses harboring slowAMPA receptors could have unique roles in hippocampal function.

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