Calcium-calmodulin signalling pathway up-regulates glutamatergic synaptic function in non-pyramidal, fast spiking rat hippocampal CA1 neurons.
1. The role of Ca(2+)-calmodulin (CaM) signalling cascades in modulating glutamatergic synaptic transmission on CA1 non-pyramidal fast-spiking neurons was investigated using whole-cell recording and perfusion in rat hippocampal slices. 2. Paired stimuli (PS), consisting of postsynaptic depolarization to 0 mV and presynaptic stimulation at 1 Hz for 30 s, enhanced excitatory postsynaptic currents (EPSCs) on non-pyramidal neurons in the stratum pyramidale (SP). The potentiation was reduced by the extracellular application of D-amino-5-phosphonovaleric acid (DAP-5, 40 microM), and blocked by the postsynaptic perfusion of 1,2-bis(2-aminophenoxy)-ethane-N,N,N',N'-tetraacetic acid (BAPTA, 10 mM), a CaM-binding peptide (100 microM) or CaMKII (281-301) (an autoinhibitory peptide of CaM-dependent protein kinases, 100 microM). 3. The application of adenophostin, an agonist of inositol trisphosphate receptors (IP(3)Rs) that evokes Ca(2+) release, into SP non-pyramidal neurons via the patch pipette (1 microM) enhanced EPSCs and occluded PS-induced synaptic potentiation. The co-application of BAPTA (10 mM) with adenophostin blocked synaptic potentiation. In addition, Ca(2+)-CaM (40:10 microM) induced synaptic potentiation, which occluded PS-induced potentiation and was attenuated by introducing CaMKII (281-301) (100 microM). EPSCs were sensitive to an antagonist of alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid receptor (AMPAR). 4. Application of Ca(2+)-CaM into SP non-pyramidal neurons induced the emergence of AMPAR-mediated EPSCs that were not evoked by low stimulus intensity before perfusion. Ca(2+)-CaM also increased the amplitude and frequency of spontaneous EPSCs. A scavenger of nitric oxide, carboxy-PTIO (30 microM in slice-perfusion solution), did not affect these increases in sEPSCs. 5. The magnitude of PS-, adenophostin- or Ca(2+)-CaM-induced synaptic potentiation in SP non-pyramidal neurons increased during postnatal development. 6. These results indicate that Ca(2+)-CaM signalling pathways in CA1 SP non-pyramidal neurons up-regulate glutamatergic synaptic transmission probably through the conversion of inactive-to-active synapses.
Wang
J H
JH
Department of Molecular Biosciences, University of Kansas, Lawrence, KS 66045, USA. jhwang@eagle.cc.ukans.edu
Kelly
P
P
D018750:6-Cyano-7-nitroquinoxaline-2,3-dione / Q000494:pharmacology; D000200:Action Potentials / Q000187:drug effects / Q000502:physiology; D000241:Adenosine / Q000031:analogs & derivatives* / Q000494:pharmacology; D000818:Animals; D002118:Calcium / Q000378:metabolism; D002120:Calcium Channel Agonists / Q000494:pharmacology; D020013:Calcium Signaling / Q000502:physiology*; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000494:pharmacology; D002147:Calmodulin / Q000378:metabolism*; D002148:Calmodulin-Binding Proteins / Q000494:pharmacology; D002478:Cells, Cultured; D002614:Chelating Agents / Q000494:pharmacology; D004533:Egtazic Acid / Q000031:analogs & derivatives / Q000494:pharmacology; D004558:Electric Stimulation; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects / Q000502:physiology; D006624:Hippocampus / Q000166:cytology / Q000254:growth & development; D007395:Interneurons / Q000166:cytology / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D018091:Receptors, AMPA / Q000378:metabolism*; D013569:Synapses / Q000502:physiology*
D002120:Calcium Channel Agonists; D002147:Calmodulin; D002148:Calmodulin-Binding Proteins; D002614:Chelating Agents; D018691:Excitatory Amino Acid Antagonists; D018091:Receptors, AMPA; C085029:adenophostin A; D004533:Egtazic Acid; D018750:6-Cyano-7-nitroquinoxaline-2,3-dione; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; D017871:Calcium-Calmodulin-Dependent Protein Kinases; C025603:1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid; D000241:Adenosine; D002118:Calcium