Multiple epsilon subunits are major determinants of the NMDA receptor channel diversity. Based on their functional properties in vitro and distributions, we have proposed that the epsilon 1 and epsilon 2 subunits play a role in synaptic plasticity. To investigate the physiological significance of the NMDA receptor channel diversity, we generated mutant mice defective in the epsilon 2 subunit. These mice showed no suckling response and died shortly after birth but could survive by hand feeding. The mutation hindered the formation of the whisker-related neuronal barrelette structure and the clustering of primary sensory afferent terminals in the brainstem trigeminal nucleus. In the hippocampus of the mutant mice, synaptic NMDA responses and longterm depression were abolished. These results suggest that the epsilon 2 subunit plays an essential role in both neuronal pattern formation and synaptic plasticity.

No abstract

1. The effects of iontophoretic application of the excitatory amino acid antagonists kynurenic acid (KYN) and DL-2-amino-5-phosphonovaleric acid (APV), as well as the monoamines serotonin (5-HT) and norepinephrine (NE), on extracellularly recorded jaw opener motoneuron [digastric motoneuron (DIG)] discharge during cortically induced rhythmical masticatory-like activity (RMA) were examined in the anesthetized guinea pig. 2. Iontophoretic application of KYN, a broad-spectrum amino acid antagonist, suppressed the motoneuronal discharge evoked by short pulse train stimulation of the cortex for most cells tested. In contrast, iontophoretic application of APV, a specific N-methyl-D-aspartate (NMDA) antagonist, was usually without effect on the motoneuronal discharge evoked by short pulse train stimulation. 3. During RMA evoked by repetitive cortical stimulation, both KYN and APV suppressed rhythmical DIG motoneuronal discharge in many cells tested. 4. These data suggest that excitatory amino acid receptors on jaw opener motoneurons are involved in activation of RMA. It is proposed that the short-latency rapid excitation of jaw opener motoneurons, which occurs during both short pulse train cortical stimulation and RMA induced by repetitive cortical stimulation, is mediated, at least in part, by non-NMDA receptors. It is further suggested that the large-amplitude, long-duration slow rhythmical oscillations, which occur in the membrane potential of jaw opener motoneurons during RMA induced by repetitive cortical stimulation, are mediated, at least in part, by NMDA receptors. 5. Iontophoretic application of NE or 5-HT with low currents (less than 20 nA) produced a facilitation of digastric motoneuronal discharge during cycle-triggered glutamate application, short pulse train cortical stimulation, and RMA evoked by repetitive cortical stimulation. These facilitatory effects on motoneuronal discharge started within 1 min of drug application, reached a peak at approximately 3 min that persisted for several minutes after the application period, and recovered to control levels within 10-15 min. Direct application of NE or 5-HT, in the absence of chemical or synaptic activation, failed to activate these motoneurons. However, iontophoretic application of either monoamine could facilitate and bring to threshold rhythmical motoneuronal discharges during subthreshold repetitive cortical stimulation. 6. Iontophoretic application of methysergide, a 5-HT antagonist, and phentolamine, an alpha adrenoreceptor blocker, both produced a selective and reversible blockade of the facilitatory effects of 5-HT and NE, respectively, on motoneuronal discharge during cortically induced RMA. In contrast, iontophoretic application of sotalol, a beta adrenoreceptor blocker, had no effect on the NE-induced facilitation of RMA.(ABSTRACT TRUNCATED AT 400 WORDS)

No abstract

No abstract