title: The importance of N-methyl-D-aspartate (NMDA) receptors in subtraction of electrosensory reafference in the dorsal nucleus of skates.
abstract: The dorsal nucleus of the little skate is a cerebellum-like sensory structure that adaptively filters out predictable electrosensory inputs. The filter's plasticity is mediated by anti-Hebbian associative depression at the synapses between parallel fibers and ascending efferent neurons (AENs). Changes in synaptic strength are indicated by the formation of a cancellation signal which is initiated by co-activation of parallel fibers and AENs, and can be reversed by parallel fiber activity in the absence of AEN activation. In other cerebellum-like sensory structures, the formation of the cancellation signal requires activation of postsynaptic NMDA receptors on the principal neurons. We demonstrate here by immunohistochemistry that the somas and the initial portion of both apical and basal dendrites of the AENs are labeled with antibodies raised against the NR1 subunit of NMDA receptors from a South American electric fish. In in vivo physiological experiments, we show that the formation of the cancellation signal induced by coupling an electrosensory stimulus to ventilatory movements or direct parallel fiber stimulation is blocked when either of the NMDA receptor antagonists 2-amino-5-phosphonovaleric acid (APV) or MK801 is injected into the molecular layer above the recorded AEN. Blocking NMDA receptors prevented formation of a cancellation signal in 79% (15/19; APV) and 60% (3/5; MK801) of the AENs. This blockage was reversible in 40% (6/15) of the AENs after APV removal. Thus, in the dorsal nucleus, the activity-dependent, long-lasting but reversible change in synaptic strength of the parallel fiber-AEN synapses appears to be an NMDA receptor-dependent process.
authors.affiliation: Biology Department, Wesleyan University, Middletown, CT 06459, USA. zzhang@wesleyan.edu
authors.forename: Zhi
authors.initials: Z
authors.lastname: Zhang
authors.forename: David
authors.initials: D
authors.lastname: Bodznick
mesh_terms: D015763:2-Amino-5-phosphonovalerate / Q000494:pharmacology; D000818:Animals; D000918:Antibody Specificity / Q000276:immunology; D016291:Dizocilpine Maleate / Q000494:pharmacology; D013058:Mass Spectrometry; D018613:Microscopy, Confocal; D009475:Neurons, Afferent / Q000187:drug effects / Q000378:metabolism*; D009476:Neurons, Efferent / Q000187:drug effects / Q000378:metabolism; D021122:Protein Subunits / Q000378:metabolism; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects; D012860:Skates, Fish / Q000378:metabolism*; D012984:Software; D013787:Thalamic Nuclei / Q000187:drug effects* / Q000378:metabolism*
chemical_list: D021122:Protein Subunits; D016194:Receptors, N-Methyl-D-Aspartate; D016291:Dizocilpine Maleate; D015763:2-Amino-5-phosphonovalerate