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Area of Science:

  • Neuroscience
  • Cellular Neuroscience
  • Systems Neuroscience

Background:

  • N-methyl-D-aspartate receptors (NMDARs) are critical for excitatory neurotransmission, found both synaptically and extrasynaptically.
  • The striatum, a basal ganglia nucleus, receives substantial glutamatergic input, leading to high extracellular glutamate levels that can activate extrasynaptic NMDARs.

Purpose of the Study:

  • To investigate the role of extrasynaptic NMDARs in cortically evoked responses and NMDAR-stimulated activity within striatal neurons.
  • To determine the impact of memantine, an extrasynaptic NMDAR antagonist, on striatal neuronal network activity.

Main Methods:

  • Electrophysiological recordings in striatal neurons to measure cortically induced NMDA excitatory currents.
  • Utilized fluorescent calcium indicators and multielectrode arrays (MEAs) to assess network behavior and NMDA-induced currents.
  • Cultured segregated cortical and striatal neurons on MEAs to study network interactions and the effects of memantine.

Main Results:

  • Memantine dose-dependently reduced cortically induced NMDA excitatory currents in striatal neurons.
  • Memantine significantly inhibited NMDAR-dependent membrane potential oscillations (up and down states).
  • In network recordings, memantine reduced NMDA-induced excitatory currents and overall network behavior, particularly affecting fast-spiking interneurons.

Conclusions:

  • Extrasynaptic NMDARs play a significant role in regulating striatal neuronal network activity.
  • Memantine effectively modulates striatal function by targeting extrasynaptic NMDARs.
  • These findings underscore the importance of extrasynaptic receptor function in basal ganglia circuits.