Kazuhisa Ichikawa

Effect of phospholipase Cβ4 lacking in thalamic neurons on electroencephalogram

Activity of thalamic neurons has been shown to be modulated via type-1 metabotropic glutamate receptor (mGluR1) activation, which initiates an intracellular Ca signaling cascade involving phospholipase Cbeta4 (PLCbeta4) and leading to the activation of conventional protein kinase C (cPKC). In the present study, we investigated the role of PLCbeta4 in thalamic neuron. PLCbeta4-deficient mutant mice were found to exhibit three phenotypic characteristics: (1) a 2-Hz increase in the peak frequency of electroencephalogram (EEG) of rapid eye movement (REM) sleep, (2) an increase in the frequency of miniature excitatory postsynaptic currents (mEPSCs) recorded in thalamus, and (3) waveform distortion of EEG. We postulate here that changes in protein phosphorylation due to reduced cPKC activity by PLCbeta4 deletion in thalamic neurons may give rise to these phenotypic characteristics. Taken together, these results indicate that reduced PLCbeta4 activity in thalamic neurons may underlie high-cortical oscillation frequency.

Localization of activated Ca2+/calmodulin-dependent protein kinase II within a spine: modeling and computer simulation

Abstract Ca 2+ /calmodulin-dependent protein kinase II (CaMKII) plays a crucial role in the induction of long-term potentiation (LTP). One form of LTP expression is thought to be the phosphorylation of glutamate receptor channels by CaMKII. Thus the localization of activated CaMKII within a spine will affect the expression of LTP. The translocation of activated CaMKII to PSD was reported. Here we investigated the localization of activated CaMKII in a model dendritic spine, and found that the diffusion of calmodulin and calcineurin but not CaMKII contribute to the localization of activated CaMKII near PSD. This will offer an additional mechanism for the localization.

Characteristics of glutamate receptors of rat cerebellar purkinje cell

Extracellular application of either quisqualic acid (QA) or Phe-Met-Arg-Phe-NH1 (FMRFamide) to the identified neurons of Aplysia ganglion elicits a slow K’-current response under voltage clamp. The QA-induced K’-current response was markedly depressed in the presence of CNQX, an antagonist for non-NMDA receptors. On the other hand, application of kainate and AMPA, agonists for non-NMDA receptors, did not induce any significant response in the same neurons. QA-induced Kf-current response was not depressed at all by intracellular injection of guanosine S--O-(2-thiodiphosphate) (GDP@), while the FMRFamide-induced response was completely blocked by GDP-OS in the same cell. However. both the QAand FMRFamide-induced K’-current responses decreased markedly when the temperature was lowered to 15 “C from 22 “C. These results indicate that the QA-induced Kt-current response does not conform in its pharmacological characteristics to any of the known glutamate-induced responses in vertebrate.

1328 Amplification of switching characteristics of intracellular biochemical-reaction networks involving CaMKII

Takanori Hashimoto, Yasushi Kajii, Toru Nishikawa Psychostimulants elicit a progressive and persistent enhancement of behavioral responses to these drugs (behavioral sensitization). To get an insight into the possible involvement of neuronal plasticit,y in the behavioral sensitization, we studied the effects of single administration of MAP and cocaine on the expression of a plasticity-related molecule, tissue plasminogen activator (TPA) mRNA. An acute injection of MAP and cocaine induced TPA mRNA in a subpopulation of neurons in the mediodorsal frontal cortex, agranular insular cortex and piriform cortex. Similar distribution and time course of TPA mRNA expression was seen after systemic application of nomifensine and phencyclidine which are also capable to produce sensitization. Pretreatment with dopamine receptor antagonists, haloperidol and SCH23390, inhibited MAP-induced TPA mRNA expression. Retrograde tracer study combined with in situ hybridization revealed majority of TPA mRNA expressing cells project to the medial striatum.

1313 A model for the differentiation of LTP and LTD: Differential activity of CaMKII and calcineurin to large and moderate rise in [Ca2+]i

Hironobu Sakaguchi1~2, Ayako Yamaguchi1v2 Male zebra finch learns to imitate a memorized song template using auditory feedback from its own vocalization, during a sensitive period. Song behavior is produced by two functionally distinct neural pathways, which are important for song acquisition and production. The two pathways converge in the robust nucleus of the archistriatum (RA) at the time when song learning begins. During auditory-based vocal learning, there are formation and reorganization of song-related neural circuits. However, it is unknown what molecular changes occur during the sensitive period and how auditory experience affects the circuits. In this report, we found a transient increase of the enzyme activity of protein kinase C (PKC) in the RA during a sensitive period. Interestingly, early deafening by chohelar removal inhibit the increase of PKC enzyme activity. It suggests that PKC is important for song learning in the zebra finch.

2321 Differential activity of CaMKII and calcineurin to the rise in [Ca2+]i

Long-term potentiation (LIT) and depression (LID) share some common molecular mechanisms. Both requires rise in [Ca2+]i. The large rise in [Ca’+]i is thought to result in LTF’, while moderate rise results in LTD. A model was proposed in which the large and moderate rise in [Ca2+]i resulted in the net phosphorylation and dephosphorylation of CaMKU leadiig to its onand off-state, respectively. In one hypothesis, however, the differentiation of LTP and LTD are assumed to he resulted from the difference in the activity of kinase and phosphatase. In the present study, we analyzed the activities of CaMKII and calcineurin from a chemical reaction model. In the present model, CaMKII is assumed to he activated by the biding of Ca2+-bound calmodulin, and calcineurin is assumed to be activated by the binding of Ca2+ and Caz+-bound calmodulin. The steady state analysis of a simplified model and numerical simulations have shown that the activity of CaMKII was lower than calcineurin by the moderate rise in [Ca2+]i, while it was reversed at the large rise in [Ca2+]i. It was found that this differentiation of the activities was due to the activation pathways of Cah4KIl and calcineurin with a certain range of parameters. ‘Ihe reported dissociation constants for CaMKU and calcineurin were found to be well within this range.