title: D-cycloserine enhances both intrinsic excitability of CA1 hippocampal neurons and expression of activity-regulated cytoskeletal (Arc) protein.
abstract: The interaction of NMDA receptor (NMDAR) activation and other mechanisms regulating neuronal excitability have not been thoroughly described. While excess activation of NMDARs results in excitotoxicity, partial activation of NMDARs by d-cycloserine (DCS) is nootropic, enhancing both acquisition and extinction of memories. The mechanism by which DCS treatment enhances memory is unclear. NMDAR activation has been shown to increase expression of the activity-regulated cytoskeletal (Arc) protein associated with neural plasticity and enhanced memory. Enhanced memory is also associated with increases in neuronal intrinsic excitability, i.e. reductions in post-burst afterhyperpolarizations (AHPs) after acquisition of new tasks. Reductions in AHPs can occur when Ca(2+) influx is reduced. This study aimed to determine if either if Arc expression, intrinsic excitability, or both were altered following systemic administration of a memory-enhancing dose of DCS, i.e. what form of plasticity would be exhibited. Both Arc protein expression and intrinsic excitability were enhanced in tissue prepared 1h post-administration of a nootropic dose of DCS. Both mechanisms have been strongly associated with memory enhancement, but have not previously been demonstrated to change across the same time frame in the same preparation in response to DCS treatment.
authors.affiliation: University of Texas at Dallas, Cognition & Neuroscience, Behavioral & Brain Sciences, 800 W. Campbell Rd., Richardson, TX 75080-3021, United States. Electronic address: elissa@donzis.com.
authors.forename: E J
authors.initials: EJ
authors.lastname: Donzis
authors.affiliation: University of Texas at Dallas, Cognition & Neuroscience, Behavioral & Brain Sciences, 800 W. Campbell Rd., Richardson, TX 75080-3021, United States. Electronic address: tres@utdallas.edu.
authors.forename: L T
authors.initials: LT
authors.lastname: Thompson
mesh_terms: D000200:Action Potentials; D000818:Animals; D056547:CA1 Region, Hippocampal / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D003523:Cycloserine / Q000494:pharmacology*; D003598:Cytoskeletal Proteins / Q000378:metabolism*; D008297:Male; D008564:Membrane Potentials; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D009474:Neurons / Q000187:drug effects* / Q000502:physiology; D018697:Nootropic Agents / Q000494:pharmacology*; D018408:Patch-Clamp Techniques; D020318:Rats, Long-Evans
chemical_list: D003598:Cytoskeletal Proteins; D009419:Nerve Tissue Proteins; D018697:Nootropic Agents; C092069:activity regulated cytoskeletal-associated protein; D003523:Cycloserine
keywords: Activity Regulated Cytoskeletal Protein; Afterhyperpolarization; Hippocampus; Intrinsic excitability; NMDA receptor; d-Cycloserine