several studies point to an important function of cyclooxygenase (cox) and prostaglandin signaling in models of synaptic plasticity which is associated with n-methyl-d-aspartate receptors (nmdars). cyclooxygenase gene is suggested to be an immediate early gene that is tightly regulated in neurons by nmda dependent synaptic activity. nonsteroid antiinflammatory drugs (nsaids) exert their antiinf...

Calcium/calmodulin dependent protein kinase II (CaMKII) is implicated to play a key role in learning and memory. NR2B subunit of N-methyl-D-aspartate receptor (NMDAR) is a high affinity binding partner of CaMKII at the postsynaptic membrane. NR2B binds to the T-site of CaMKII and modulates its catalysis. By direct measurement using isothermal titration calorimetry (ITC), we show that NR2B bindi...

Binding of CaMKII (Ca(2+)/calmodulin-dependent protein kinase II) to the NR2B subunit of the NMDAR (N-methyl-D-aspartate-type glutamate receptor) in the PSD (postsynaptic density) is essential for the induction of long-term potentiation. In this study, we show that binding of NR2B to the T-site (Thr(286)-autophosphorylation site binding pocket) of CaMKII regulates its catalysis as reflected in ...

In many brain regions involved in learning NMDA receptors (NMDARs) act as coincidence detectors of pre- and postsynaptic activity, mediating Hebbian plasticity. Intriguingly, the parallel fiber (PF) to Purkinje cell (PC) input in the cerebellar cortex, which is critical for procedural learning, shows virtually no postsynaptic NMDARs. Why is this? Here, we address this question by generating and...

Metaplasticity, the adaptive changes of long-term potentiation (LTP) and long-term depression (LTD) in response to fluctuations in neural activity is well documented in visual cortex, where dark rearing shifts the frequency threshold for the induction of LTP and LTD. Here we studied metaplasticity affecting spike-timing-dependent plasticity, in which the polarity of plasticity is determined not...

The plasticity of synapses within neural circuits is regulated by activity, but the underlying mechanisms remain elusive. Using the dye FM1-43 to directly image presynaptic function, we found that large numbers of presynaptic terminals in hippocampal cultures have a low release probability. While these terminals were not readily modifiable, a transient but not permanent long-term reduction of n...

Ca influx through NMDA receptors (NMDARs) triggers synaptic plasticity, gene transcription, and cytotoxicity, but little is known about the regulation of NMDA-Rs themselves. We used two-photon glutamate uncaging to activate NMDA-Rs on individual dendritic spines in rat CA1 neurons while we measured NMDAR currents at the soma and [Ca] changes in spines. Low-frequency uncaging trains induced Ca-d...

NMDA receptors (NMDARs) mediate ischemic brain damage, for which interactions between the C termini of NR2 subunits and PDZ domain proteins within the NMDAR signaling complex (NSC) are emerging therapeutic targets. However, expression of NMDARs in a non-neuronal context, lacking many NSC components, can still induce cell death. Moreover, it is unclear whether targeting the NSC will impair NMDAR...

Damaging interactions between antibodies and brain antigenic targets may be responsible for an expanding range of neurological disorders. In the case of systemic lupus erythematosus (SLE), patients generate autoantibodies (AAbs) that frequently bind dsDNA. Although some symptoms of SLE may arise from direct reactivity to dsDNA, much of the AAb-mediated damage originates from cross-reactivity wi...

Visual recognition memory relies on long-term depression-like mechanisms within the perirhinal cortex and the activation of the lateral amygdala can enhance visual recognition memory. How the lateral amygdala regulates recognition memory is not known, but synaptic plasticity at amygdala-perirhinal synapses may provide a mechanism for the emotional enhancement of recognition memory. In this stud...