Effects of auditory priming on CA3 pyramidal neurons of Noda epileptic rats (NER)

AbstractWhile efficient methods are well established for studying postsynaptic protein regulation of glutamatergic synapses in the mammalian central nervous system, similarly efficient methods are lacking for studying proteins regulating presynaptic function. In the present study, we introduce an optical/electrophysiological method for investigating presynaptic molecular regulation. Here, using an optogenetic approach, we selectively stimulate genetically modified presynaptic CA3 pyramidal neurons in the hippocampus and measure optically-induced excitatory postsynaptic currents produced in unmodified postsynaptic CA1 pyramidal neurons. While such use of optogenetics is not novel, previous implementation methods do not allow basic quantification of the changes in synaptic strength produced by genetic manipulations. We find that incorporating simultaneous recordings of fiber volley amplitude provides a control for optical stimulation intensity and, as a result, creates a metric of synaptic efficacy that can be compared across experimental conditions. In the present study, we utilize our new method to demonstrate that inhibition of synaptotagmin 1 expression in CA3 pyramidal neurons leads to a significant reduction in Schaffer collateral synapse function, an effect that is masked with conventional electrical stimulation. Our hope is that this method will expedite our understanding of molecular regulatory pathways that govern presynaptic function.

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Liraglutide modulates GABAergic signaling in rat hippocampal CA3 pyramidal neurons predominantly by presynaptic mechanism

BMC Pharmacology and Toxicology ◽

10.1186/s40360-017-0191-0 ◽

2017 ◽

Vol 18 (1) ◽

Cited By ~ 9

Author(s):

Omar Babateen ◽

Sergiy V. Korol ◽

Zhe Jin ◽

Amol K. Bhandage ◽

Aikeremu Ahemaiti ◽

...

Keyword(s):

Pyramidal Neurons ◽

Hippocampal Ca3 ◽

Ca3 Pyramidal Neurons

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Analysis of voltage-gated and synaptic conductances contributing to network excitability defects in the mutant mouse tottering

Journal of Neurophysiology ◽

10.1152/jn.1994.71.1.1 ◽

1994 ◽

Vol 71 (1) ◽

pp. 1-10 ◽

Cited By ~ 16

Author(s):

S. A. Helekar ◽

J. L. Noebels

Keyword(s):

Gabaa Receptor ◽

Pyramidal Neurons ◽

Hippocampal Slices ◽

Channel Blockers ◽

Gamma Aminobutyric Acid ◽

Voltage Gated ◽

Voltage Dependent ◽

Prolonged Duration ◽

Ca3 Pyramidal Neurons ◽

The Difference

1. Intracellular current- and voltage-clamp recordings were carried out in CA3 pyramidal neurons from hippocampal slices of adult tg/tg mice and their coisogenic C57BL/6J (+/+) controls with the use of the single-electrode switch-clamp technique. The principal aim of this study was to investigate the mechanisms responsible for the tg gene-linked prolongation (mean 60%) of a giant synaptic response, the potassium-induced paroxysmal depolarizing shift (PDS) at depolarized membrane potentials (Vm -47 to -54 mV) during synchronous network bursting induced by 10 mM potassium ([K+]o). 2. To examine the role of intrinsic voltage-dependent conductances underlying the mutant PDS prolongation, neurons were voltage clamped by the use of microelectrodes filled with 100 mM QX-314 or QX-222 chloride (voltage-gated sodium channel blockers) and 2 M cesium sulphate (potassium channel blocker). The whole-cell currents active during the PDS showed a significantly prolonged duration (mean 34%) at depolarized Vms in tg/tg compared with +/+ cells, indicating that a defect in voltage-dependent conductances is unlikely to completely account for the mutant phenotype. 3. Bath application of 40 microM (DL)-2-aminophosphonovalerate (DL-APV) produced a 30% reduction in PDS duration in both genotypes but failed to significantly alter the tg gene-linked prolongation compared with the wild type. These data indicate that the mutant PDS abnormality does not result from a selective increase of the N-methyl-D-aspartate (NMDA) receptor-mediated excitatory synaptic component. 4. Blockade of gamma-aminobutyric acid-A (GABAA) transmission with picrotoxin (50 microM) or bicuculline (1–5 microM) completely eliminated the difference in PDS duration between the genotypes. Furthermore, although both GABAA receptor antagonists increased the mean PDS duration in +/+ neurons, they did not significantly alter it in tg/tg neurons. These findings are consistent with a reduction in GABAA receptor-mediated synaptic inhibition during bursting in the tg CA3 hippocampal network. 5. To test this hypothesis, bursting CA3 pyramidal neurons were loaded intracellularly with chloride by the use of KCl-filled microelectrodes to examine the effect of reversing the hyperpolarizing chloride-dependent GABAA receptor-mediated inhibitory postsynaptic component of the PDS. Chloride loading prolonged PDS duration in both genotypes, but the increase was greater in +/+ than in tg/tg neurons, indicating that a smaller GABAA inhibitory postsynaptic potential (IPSP) component was reversed in the mutant.(ABSTRACT TRUNCATED AT 400 WORDS)

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Computational Analysis of the Impact of Chronic Stress on Intrinsic and Synaptic Excitability in the Hippocampus

Journal of Neurophysiology ◽

10.1152/jn.00913.2009 ◽

2010 ◽

Vol 103 (6) ◽

pp. 3070-3083 ◽

Cited By ~ 19

Author(s):

Rishikesh Narayanan ◽

Sumantra Chattarji

Keyword(s):

Chronic Stress ◽

Pyramidal Neurons ◽

Three Dimensional ◽

Input Resistance ◽

Synaptic Potentiation ◽

Synaptic Inputs ◽

Hippocampal Ca3 ◽

Ca3 Pyramidal Neurons ◽

Dendritic Atrophy ◽

The Impact

Dendritic atrophy and impaired long-term synaptic potentiation (LTP) are hallmarks of chronic stress-induced plasticity in the hippocampus. It has been hypothesized that these disparate structural and physiological correlates of stress lead to hippocampal dysfunction by reducing postsynaptic dendritic surface, thereby adversely affecting the availability of synaptic inputs and suppressing LTP. Here we examine the validity of this framework using biophysical models of hippocampal CA3 pyramidal neurons. To statistically match with the experimentally observed region specificity of stress-induced atrophy, we use an algorithm to systematically prune three-dimensional reconstructions of CA3 pyramidal neurons. Using this algorithm, we build a biophysically realistic computational model to analyze the effects of stress on intrinsic and synaptic excitability. We find that stress-induced atrophy of CA3 dendrites leads to an increase in input resistance, which depends exponentially on the percentage of neuronal atrophy. This increase translates directly into higher spiking frequencies in response to both somatic current injections and synaptic inputs at various locations along the dendritic arbor. Remarkably, we also find that the dendritic regions that manifest atrophy-induced synaptic hyperexcitability are governed by the region specificity of the underlying dendritic atrophy. Coupled with experimentally observed modulation of N-methyl-d-aspartate receptor currents, such hyperexcitability could tilt the balance of plasticity mechanisms in favor of synaptic potentiation over depression. Thus paradoxically, our results suggest that stress may impair hippocampal learning and memory, not by directly inhibiting LTP, but because of stress-induced facilitation of intrinsic and synaptic excitability and the consequent imbalance in bidirectional synaptic plasticity.

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Hippocampal mossy fiber activity evokes Ca2+ release in CA3 pyramidal neurons via a metabotropic glutamate receptor pathway

Neuroscience ◽

10.1016/s0306-4522(01)00293-7 ◽

2001 ◽

Vol 107 (1) ◽

pp. 59-69 ◽

Cited By ~ 62

Author(s):

A Kapur ◽

M Yeckel ◽

D Johnston

Keyword(s):

Glutamate Receptor ◽

Pyramidal Neurons ◽

Metabotropic Glutamate Receptor ◽

Mossy Fiber ◽

Metabotropic Glutamate ◽

Ca3 Pyramidal Neurons

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Giant Depolarizing Potentials Trigger Transient Changes in the Intracellular Cl- Concentration in CA3 Pyramidal Neurons of the Immature Mouse Hippocampus

Frontiers in Cellular Neuroscience ◽

10.3389/fncel.2018.00420 ◽

2018 ◽

Vol 12 ◽

Cited By ~ 7

Author(s):

Aniello Lombardi ◽

Peter Jedlicka ◽

Heiko J. Luhmann ◽

Werner Kilb

Keyword(s):

Pyramidal Neurons ◽

Mouse Hippocampus ◽

Immature Mouse ◽

Ca3 Pyramidal Neurons

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Synapse type-specific proteomic dissection identifies IgSF8 as a hippocampal CA3 microcircuit organizer

10.1101/846816 ◽

2019 ◽

Cited By ~ 1

Author(s):

Nuno Apóstolo ◽

Samuel N. Smukowski ◽

Jeroen Vanderlinden ◽

Giuseppe Condomitti ◽

Vasily Rybakin ◽

...

Keyword(s):

Cell Surface ◽

Pyramidal Neurons ◽

Mossy Fiber ◽

Surface Protein ◽

Guidance Cue ◽

Hippocampal Ca3 ◽

Cell Surface Interactions ◽

Ca3 Pyramidal Neurons ◽

Ca3 Neurons ◽

Multiple Ligand

SummarySynaptic diversity is a key feature of neural circuits. The structural and functional diversity of closely spaced inputs converging on the same neuron suggests that cell-surface interactions are essential in organizing input properties. Here, we analyzed the cell-surface protein (CSP) composition of hippocampal mossy fiber (MF) inputs on CA3 pyramidal neurons to identify regulators of MF-CA3 synapse properties. We uncover a rich cell-surface repertoire that includes adhesion proteins, guidance cue receptors, extracellular matrix (ECM) proteins, and uncharacterized CSPs. Interactome screening reveals multiple ligand-receptor modules and identifies ECM protein Tenascin-R (TenR) as a ligand of the uncharacterized neuronal receptor IgSF8. Presynaptic Igsf8 deletion impairs MF-CA3 synaptic architecture and robustly decreases the density of bouton filopodia that provide feedforward inhibition of CA3 neurons. Consequently, loss of IgSF8 increases CA3 neuron excitability. Our findings identify IgSF8 as a regulator of CA3 microcircuit development and suggest that combinations of CSP modules define input identity.

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