Guinea-pig CA1 Research Articles

Reduction of human neocortical and guinea pig CA1-neuron A-type currents by organic calcium channel blockers

In epilepsy models, organic calcium antagonists regularly induce a transient activity increase before suppression of epileptiform discharges. This action was speculated to be mediated by a modulation of potassium currents. Since A-type currents potently regulate neuronal excitability, their modulation by calcium channel blockers was investigated in acutely isolated human neocortical temporal lobe neurons and CA1 neurons of guinea pigs using the whole-cell voltage-clamp technique. In human neurons, 40 μM nifedipine caused an amplitude reduction by 28% at a command potential of −6 mV and produced a biexponential, markedly accelerated current inactivation with time constants of 8.4 ± 1.1 ms ( n = 6) and 62.9 ± 6.4 ms ( n = 5). The time constant under control conditions was 50.1 ± 8.5 ms ( n = 6). Verapamil (40 μM) did not affect the current amplitude, but accelerated the monoexponential current inactivation from 40.2 ± 7.1 ms to 13.3 ± 0.8 ms ( n = 9). Accordingly, verapamil accelerated the inactivation from 42.3 ± 5.9 ms to 15.0 ± 1.3 ms ( n = 11) in guinea pig CA1 neurons, without affecting the current amplitude. In this preparation, it was shown that the two enantiomers of verapamil do not differ in their actions. The results show that the A-type current in human neocortical and in guinea pig hippocampal neurons is reduced by organic calcium channel blockers.

Tetanic LTP in guinea pig CA1 is associated with an increase in the NMDA receptor-mediated component of EPSCs and in the rate of depression by MK-801

Tetanic LTP in guinea pig CA1 is associated with an increase in the NMDA receptor-mediated component of EPSCs and in the rate of depression by MK-801

Tests of the roles of two diffusible substances in long-term potentiation: evidence for nitric oxide as a possible early retrograde messenger.

Although long-term potentiation (LTP) in the CA1 region of the hippocampus is initiated postsynaptically by the influx of Ca2+ through N-methyl-D-aspartate receptor channels, the maintenance of LTP seems to be at least in part presynaptic. This suggests that the postsynaptic cell releases a retrograde messenger to activate the presynaptic terminals. It is likely that this messenger is membrane-permeant and reaches the presynaptic neuron by diffusion. We therefore have investigated two major membrane-permeant candidate retrograde messengers, arachidonic acid and nitric oxide (NO). Consistent with arachidonic acid or a lipoxygenase metabolite being a retrograde messenger, the phospholipase A2 and lipoxygenase inhibitor nordihydroguaiaretic acid blocked LTP in the guinea pig CA1 region in vitro. However, arachidonic acid (up to 100 microM) did not reliably produce activity-independent LTP, and activity-dependent potentiation by arachidonic acid was blocked by DL-aminophosphonovaleric acid. Since nordihydroguaiaretic acid also interferes with signal transduction involving NO, we next examined whether inhibitors of NO synthase block LTP. NG-Nitro-L-arginine blocked LTP when given in the bath, and this inhibition was partially overcome by high concentrations of L-arginine, suggesting that the inhibitor is specific to NO synthase. NG-Nitro-L-arginine and NG-methyl-L-arginine (but not NG-methyl-D-arginine) also blocked LTP when injected intracellularly, indicating that NO synthase is located in the postsynaptic cell. The NO, in turn, seems to be released into the extracellular space, since bathing the slice with hemoglobin, a protein that binds NO and is not taken up by cells, also blocked LTP. Moreover, NO enhances spontaneous presynaptic release of transmitter from hippocampal neurons in dissociated cell culture. These data favor the idea that NO might be a retrograde messenger in LTP.

Optical imaging of calcium accumulation in hippocampal pyramidal cells during synaptic activation.

The dynamic response of nerve cells to synaptic activation and the spatial distribution of biochemical processes regulated by ion concentration are critically dependent on the cell-surface distribution of ion channels. In the hippocampus, intracellular calcium-ion concentration is thought to influence the biochemical events associated with kindling, excitotoxicity, and long-term potentiation. Computer models of hippocampal pyramidal cells also indicate that calcium-channel location influences dynamic characteristics such as bursting. Here, we have used in situ microfluorometric imaging in brain slices to directly measure the spatial distribution of calcium accumulation in guinea-pig CA1 pyramidal cells during trains of orthodromic synaptic stimulation. Calcium accumulation is substantial throughout the entire proximal section of the apical and basal dendrites. Most of this accumulation results from influx through non-NMDA (N-methyl-D-aspartate) voltage-gated calcium channels, and in the apical dendrite it drops steeply as the dendrite enters stratum moleculare, the termination zone of perforant path afferents. These results demonstrate a marked segregation of calcium-channel activity and directly show a spatial distribution of calcium accumulation during orthodromic synaptic activation.

Novel recognition site for l-quisqualate sensitizes neurons to depolarization by l-2-amino-4-phosphonobutanoate ( l-AP4)

Brief exposure of rat hippocampal slices to l-quisqualate sensitizes pyramidal neurons to depolarization by l-2-amino-4-phosphonobutanoate ( l-AP4). We report here experiments designed to clarify the duration, pharmacology, mechanism, and pathway specificity of this ‘QUIS-effect’. The quisqualate-induced sensitization to l-AP4 decreases only 3-fold over a 4 h period. No compound besides quisqualate has been found to induce the QUIS-effect, including quisqualate analogues, potent excitatory amino acid agonists, l-glutamate, l-aspartate, and compounds known to stimulus second messenger systems in hippocampal slices. Of 43 compounds assayed here, only 5 are able to block the induction of the QUIS-effect. Although these blockers are also potent ligands at a chloride-dependent glutamate uptake site, the marked difference in rank ordering of compounds for QUIS-effect blockade and uptake site potency suggests that the QUIS-effect is not induced through this uptake site. The QUIS-effect can be induced in the CA1 region, the medial perforant path, and the lateral olfactory tract of the rat, and in the guinea pig CA1. It cannot be induced in the l-AP4-sensitive rat lateral perforant path (LPP), suggesting that the receptors for l-AP4 in the LPP may be distinct from those that are sensitized by quisqualate in the other pathways.

Direct afferent excitation and long-term potentiation of hippocampal interneurons.

Direct afferent excitation and long-term potentiation of hippocampal interneurons.

Electrophysiological characterization of remote chemical synapses.

Electrophysiological characterization of remote chemical synapses.N T Carnevale, and D JohnstonN T Carnevale, and D JohnstonPublished Online:01 Apr 1982https://doi.org/10.1152/jn.1982.47.4.606MoreSectionsPDF (3 MB)Download PDF ToolsExport citationAdd to favoritesGet permissionsTrack citations ShareShare onFacebookTwitterLinkedInWeChat Previous Back to Top Next Download PDF FiguresReferencesRelatedInformation Cited ByPyMUS: Python-Based Simulation Software for Virtual Experiments on Motor Unit System11 April 2018 | Frontiers in Neuroinformatics, Vol. 12Differential processing in modality-specific Mauthner cell dendrites18 December 2017 | The Journal of Physiology, Vol. 596, No. 4When complex neuronal structures may not matter6 February 2017 | eLife, Vol. 6Long-Lasting Context Dependence Constrains Neural Encoding Models in Rodent Auditory CortexHiroki Asari, and Anthony M. Zador1 November 2009 | Journal of Neurophysiology, Vol. 102, No. 5Agonist-Dependent Postsynaptic Effects of Opioids on Miniature Excitatory Postsynaptic Currents in Cultured Hippocampal NeuronsDezhi Liao, Olga O. Grigoriants, Horace H. Loh, and Ping-Yee Law1 February 2007 | Journal of Neurophysiology, Vol. 97, No. 2Distal Gap Junctions and Active Dendrites Can Tune Network DynamicsFernanda Saraga*, Leo Ng*, and Frances K. Skinner1 March 2006 | Journal of Neurophysiology, Vol. 95, No. 3Depressed Responses of Facilitatory SynapsesYoav Banitt, Kevan A. C. Martin, and Idan Segev1 July 2005 | Journal of Neurophysiology, Vol. 94, No. 1Contribution of Ih and GABAB to Synaptically Induced Afterhyperpolarizations in CA1: A Brake on the NMDA ResponseNonna A. Otmakhova, and John E. Lisman1 October 2004 | Journal of Neurophysiology, Vol. 92, No. 4High Ih Channel Density in the Distal Apical Dendrite of Layer V Pyramidal Cells Increases Bidirectional Attenuation of EPSPsThomas Berger*, Matthew E. Larkum*, and Hans-R. Lüscher*1 February 2001 | Journal of Neurophysiology, Vol. 85, No. 2Dendrosomatic Voltage and Charge Transfer in Rat Neocortical Pyramidal Cells In VitroDaniel Ulrich, and Christian Stricker1 September 2000 | Journal of Neurophysiology, Vol. 84, No. 3Synaptic Control of Motoneuronal ExcitabilityJens C. Rekling*, Gregory D. Funk*, Douglas A. Bayliss, Xiao-Wei Dong, and Jack L. Feldman4 January 2000 | Physiological Reviews, Vol. 80, No. 2Passive Normalization of Synaptic Integration Influenced by Dendritic ArchitectureDavid B. Jaffe, and Nicholas T. Carnevale1 December 1999 | Journal of Neurophysiology, Vol. 82, No. 6Determining the Activation Time Course of Synaptic AMPA Receptors from Openings of Colocalized NMDA ReceptorsBiophysical Journal, Vol. 77, No. 3Temporal overlap of excitatory and inhibitory afferent input in guinea-pig CA1 pyramidal cells8 September 2004 | The Journal of Physiology, Vol. 516, No. 2Passive electrotonic properties of rat hippocampal CA3 interneurones8 September 2004 | The Journal of Physiology, Vol. 515, No. 3Integration of Excitatory Postsynaptic Potentials in Dendrites of Motoneurons of Rat Spinal Cord Slice CulturesMatthew E. Larkum, Thomas Launey, Alexander Dityatev, and Hans-R. Lüscher1 August 1998 | Journal of Neurophysiology, Vol. 80, No. 2Comparative Electrotonic Analysis of Three Classes of Rat Hippocampal NeuronsNicholas T. Carnevale, Kenneth Y. Tsai, Brenda J. Claiborne, and Thomas H. Brown1 August 1997 | Journal of Neurophysiology, Vol. 78, No. 2Electro-geometrical coupling in non-uniform branching dendritesBiological Cybernetics, Vol. 74, No. 1Hebbian learning is jointly controlled by electrotonic and input structure9 July 2009 | Network: Computation in Neural Systems, Vol. 5, No. 1Efficient mapping from neuroanatomical to electrotonic space9 July 2009 | Network: Computation in Neural Systems, Vol. 5, No. 1Kinetics of diffusion in a spherical cell. i. no solute bufferingJournal of Neuroscience Methods, Vol. 41, No. 3Ionic and synaptic mechanisms underlying a brainstem oscillator: An in vitro study of the pacemaker nucleus of ApteronotusJournal of Comparative Physiology A, Vol. 168, No. 5Identification problems in distributed parameter neuron modelsAutomatica, Vol. 26, No. 4Whole cell recording from neurons in slices of reptilian and mammalian cerebral cortexJournal of Neuroscience Methods, Vol. 30, No. 3The role of dendritic diameters in maximizing the effectiveness of synaptic inputsBrain Research, Vol. 478, No. 1Numerical analysis of electrotonus in multicompartmental neuron modelsJournal of Neuroscience Methods, Vol. 19, No. 1 More from this issue > Volume 47Issue 4April 1982Pages 606-21 https://doi.org/10.1152/jn.1982.47.4.606PubMed7069456History Published online 1 April 1982 Published in print 1 April 1982 Metrics

Electrophysiology of hippocampal neurons. I. Sequential invasion and synaptic organization.

Electrophysiology of hippocampal neurons. I. Sequential invasion and synaptic organization.