BSI summer lecture 06thJuly FridayDr. Shigetada Nakanishi
Role of glutamate transmisstion1. brain function such as memory, learining , movement perception and cognition2. development, generation3. neurotoxicity
Ionotropic receptorsAMPA/kainate receptorrapidNMDA receptorCa** permeable receptorsMetabotropic receptors (mGluRs)G-rotein-coupled receptors
contrauctioon of a cDNA bank from brNAin vitro mRNA synthesiselectrophysiological measurement in mRNA-injectied oocytecloning of a functional cDNA by repeated fractionation of a response-positive cDNA mixture
NMDAR1 NMDAR2A,2B,2C,2DAMPA-selective(9)GluR1,R2,R3,R4Kainate-selectiveFluR5,6,7-?mGluR
NR1 expression in the hipocumpasNR2 cortex and hippocampus2C cereberalGroup1mGluR1/5 IP3/Ca++ DHOPG/MPEP/Quisqualate postsynapticGroup2 cGMPGroup3 cGMP
Selective expression of mGluR1 and mGluR2 in the cerebellum
photoreceptormGluR6はvisualでとても重要な役割をしている。bipolar cellには、2つある。off and on bipolar cells。2つは、同じようにglutamateでphotoreceptorに入力するが、結果は違うものになる。mGllluR6KOmiceは、ON responseを機能不全にする。でも、off signal(暗くすると反応する細胞)には、全く関係ない。
OPTOKINETIC NYSTAGMUS30:1の濃淡では、mGluR6KOmiceは、反応したが、2:1では、応答が起きなかった。メカニズムは、mGluR6 inhibits the TRAP cahnnel opening.
Direction-selective response of On-Off retinal ganglion cellAsymmetry between input and output of starburst cell.Starburst cellは、放射状に延びるしんけいさいぼうだが、他からの入力とbipolar cellに対する出力が偏っている。
mGluR2 is dominantly expressed in starburst cell.they can eliminateed starburst cell.In wild type, direction-selective responses happened. But starburst-eliminated cell doesn't have direction-selective response.These data indicate that starburst cells are charged for the selectivity.In the starburst cell elimination is crucial for eye moving velocity. right and left.
Decision-making experiment3つまたの迷路で、1つのゴールには、普通の飯とちょっとの危険。もう一つの方は、たくさんの飯と、たくさんの危険。どっちに行くかを調べる。
Function and dysfunction of the basal ganglia circuitryreversible neruotransmission blocking (RNB) technique for cell type-specific, reversible lblockade of transmission.pathway -specific expression of tTA using D-virus and I-viurs (promoter diffrence)Doxicyclin is nothing, tetanus toxin comes up. with Doxi suppresses toxin.tetanus toxine kills the neurons through VAMP2.virus-mediated specific expression of tetanus toxin in the direct and indirect pathways.
caocain induces hyper locomotion through D-RNB.Cocain-induced conditioned place preference.Direct pathway is crucial for cacain induced neuron function.reward-based and aversive learning
彼らは、Dopaminシグナルを調べている。Dopaminは直接と間接経路がある。直接は、LTP-D1SPにつながる。これは、striatumにある。あと、間接はLTD-D2Enkで、これは、ドーパミンがこれを阻害する。このシグナルが、globus pallidusを阻害して、SNr/VTAを阻害する。直接経路は、D1を直接活性化して、SNr/VTAを阻害する。どっちも同じ効果。結果として、SNr/VTAはThalamus, verebral cortexを活性化する。よって、reward-based learning, drug addiction
counteractive 反作用の
biological significance of two pathwways in reward and aversive behavior.
1. Animals gain rewards correctly and effectively by distinguishing between assoiative and non-associatinve rewarding stimuli2. Animals need to repidly memorize aversive to avoid aversive.
The basal gangalia networdcerebral cortex ---working memory assosciative learining habit.
basal ganlia (nucleus accambens--hippocampus(spacial learning), amygdala, septium
05July2012 サマースクールでのErin schuman (マックスプランク)の講演のメモ。
500 differenct protein species per synapse50 copyies in each protein25000 proteins per synapse104 synapses per cell250000000 proteins per celladditional 250000000 proteins in ath eaxont1/2=24hurs.Every 24hrs need atpolyribosomes are persent in or at the bases of spipnes in postsynaptic neurons harris and spacek Levy and steward 1982.BDNF kang and schuman, science 1995,1996
BDNF-induced poteintiation was blocked by anisomycin, showing local translation.5 UTR myr dGFP 3'UTR (aCamKII) Aakalu Neuron 2001local translation1. Kang and schuman 1996, BDNF2. Martin 1998 LTF in Apysia3.Huber 2000 M-GluR-dependent LTD4. Campbell and holt...
A list of 15 dendritic m RNAs identified by in situ hybriddization. steward and schuman, neuron 2003But prior stduies shows that not much overlap of mRNA. 3 group tried to looking the mRNA in dendrites but 3 group did not overlaped-mRNA.2500 mRNA estimationMany many mRNAS for synaptically-relevant proteins now identiried in the neuropil.Dendritic axon is founded the shank mRNNA with fish method.
conclusion2550 population of mRNAs that are present in the mature dendrites or axons of CA1 pyramidal neurons.estimate htat more than 50% of the mRNAs within a neuron can be detected outside of the cell body.things to think aboutmany mRNAs for proteins associated with presynaptic functionmTNA for disease -related proteinshomogeneity vs. jeterpgeneity of cell typeslocal transilation may play a fundamental role in the supply and maintenance of protiens- not just for plasticity.
Identifying and visualizing newly sythesized proteins.synaptic neuropil.Labeling of newly synthesized protiens in vivo?Ngo et al., Nature Chemical Biology, 2009
Hippocampal-Prefrontal synchrony in psychiatric disease models Joshua Godon 9th/July/2012
psychiatric disease is related to hippocampus and prefrontal cortex.HPC-PFC connectivity in psychiatric disease models.22q11 model micerecruited by anxiety schizophrenis 22q11 model miceworking memory was lower than normal one.Df(16)A+/- mice are deficient in mPFC-dHPC coherencevHPC silencing reduces dHPC-mPC cherence
dHPC-spatial memory(上の方)entorhinal cortexperirhinal cortexthalamusmPFC
vHPC--anxiety(したのほう)amygdalamPFCBNST hypothalamusventral striatum
mPFC neuron fireing patternvary in neuronsmPFC neurons encode arm type in elevated plus maze
aversive armsafe arm
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