The Depolarizing Action of GABA Controls Early Network Activity in the Developing Hippocampus

Cherubini, Enrico; Griguoli, Marilena; Safiulina, Victoria F.; Lagostena, Laura

doi:10.1007/s12035-010-8147-z

Cited by 57 publications

(49 citation statements)

References 83 publications

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“…Our numerical bifurcation analysis reveals that generically, during complex bursting, the SK2 channels conductance controls the number of small plateau oscillations (the lower g KCa , the higher the number of plateau oscillations), whereas a large contribution from CICR promotes normal spiking behavior (the higher p ER , the higher the number of large spikes). Such complex firing patterns have been observed in developing neurons (47). A generation of mixed action potential firing would produce both small transient calcium signals and larger, long-lasting signals capable of spreading to the nucleus where they may affect gene transcription pathways (48) potentially impacting on the intrinsic development of the hair cell.…”

Section: Generation Of Complex Firing Patternsmentioning

confidence: 97%

Calcium-Induced Calcium Release during Action Potential Firing in Developing Inner Hair Cells

Iosub

Avitabile

Grant

et al. 2015

Biophysical Journal

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In the mature auditory system, inner hair cells (IHCs) convert sound-induced vibrations into electrical signals that are relayed to the central nervous system via auditory afferents. Before the cochlea can respond to normal sound levels, developing IHCs fire calcium-based action potentials that disappear close to the onset of hearing. Action potential firing triggers transmitter release from the immature IHC that in turn generates experience-independent firing in auditory neurons. These early signaling events are thought to be essential for the organization and development of the auditory system and hair cells. A critical component of the action potential is the rise in intracellular calcium that activates both small conductance potassium channels essential during membrane repolarization, and triggers transmitter release from the cell. Whether this calcium signal is generated by calcium influx or requires calcium-induced calcium release (CICR) is not yet known. IHCs can generate CICR, but to date its physiological role has remained unclear. Here, we used high and low concentrations of ryanodine to block or enhance CICR to determine whether calcium release from intracellular stores affected action potential waveform, interspike interval, or changes in membrane capacitance during development of mouse IHCs. Blocking CICR resulted in mixed action potential waveforms with both brief and prolonged oscillations in membrane potential and intracellular calcium. This mixed behavior is captured well by our mathematical model of IHC electrical activity. We perform two-parameter bifurcation analysis of the model that predicts the dependence of IHCs firing patterns on the level of activation of two parameters, the SK2 channels activation and CICR rate. Our data show that CICR forms an important component of the calcium signal that shapes action potentials and regulates firing patterns, but is not involved directly in triggering exocytosis. These data provide important insights into the calcium signaling mechanisms involved in early developmental processes.

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Section: Generation Of Complex Firing Patternsmentioning

confidence: 97%

Calcium-Induced Calcium Release during Action Potential Firing in Developing Inner Hair Cells

Iosub

Avitabile

Grant

et al. 2015

Biophysical Journal

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“…This occurs primarily during the first few postnatal weeks in rodents and is determined by a changing Cl − gradient in neurons (Cherubini et al, 2011). Intracellular Cl − is relatively elevated during embryonic and early postnatal development.…”

Section: Synaptic and Cellular Disruptionsmentioning

confidence: 99%

Altered Neuronal and Circuit Excitability in Fragile X Syndrome

Contractor

Klyachko

Portera‐Cailliau

2015

Neuron

344

365

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Fragile X syndrome (FXS) results from a genetic mutation in a single gene, yet produces a phenotypically complex disorder with a range of neurological and psychiatric problems. Efforts to decipher how perturbations in signaling pathways lead to the myriad alterations in synaptic and cellular functions have provided insights into the molecular underpinnings of this disorder. From this large body of data the theme of circuit hyperexcitability has emerged as a potential explanation for many of the neurological and psychiatric symptoms in FXS. The mechanisms for hyperexcitability range from alterations in the expression or activity of ion channels to changes in neurotransmitters and receptors. Contributions of these processes are often brain region- and cell type-specific, resulting in complex effects on circuit function that manifest as altered excitability. Here, we review the current state of knowledge of the molecular, synaptic and circuit-level mechanisms underlying hyperexcitability and their contributions to the FXS phenotypes.

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“…Early in development the sodium-potassium-chloride co-transporter type 1 (NKCC1) maintains a high intracellular chloride ([Cl − ] i ) concentration in most neurons and hence Cl − -mediated synaptic events are depolarizing (Cherubini et al, 2011; Friauf et al, 2011; but see Balakrishnan et al, 2003 for an exception). It is postulated that early in development, inhibitory synapses generate excitatory postsynaptic potentials (EPSPs) that act to stabilize synapse formation, and that as neurons mature there is a switch to expression of neuronal potassium chloride co-transporter type 2 (KCC2), driving a low [Cl − ] i and supporting hyperpolarizing IPSPs (Kandler and Gillespie, 2005).…”

Section: Introductionmentioning

confidence: 99%

Nitric oxide signaling modulates synaptic inhibition in the superior paraolivary nucleus (SPN) via cGMP-dependent suppression of KCC2

Yassin

Radtke‐Schuller

Asraf

et al. 2014

Front. Neural Circuits

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Glycinergic inhibition plays a central role in the auditory brainstem circuitries involved in sound localization and in the encoding of temporal action potential firing patterns. Modulation of this inhibition has the potential to fine-tune information processing in these networks. Here we show that nitric oxide (NO) signaling in the auditory brainstem (where activity-dependent generation of NO is documented) modulates the strength of inhibition by changing the chloride equilibrium potential. Recent evidence demonstrates that large inhibitory postsynaptic currents (IPSCs) in neurons of the superior paraolivary nucleus (SPN) are enhanced by a very low intracellular chloride concentration, generated by the neuronal potassium chloride co-transporter (KCC2) expressed in the postsynaptic neurons. Our data show that modulation by NO caused a 15 mV depolarizing shift of the IPSC reversal potential, reducing the strength of inhibition in SPN neurons, without changing the threshold for action potential firing. Regulating inhibitory strength, through cGMP-dependent changes in the efficacy of KCC2 in the target neuron provides a postsynaptic mechanism for rapidly controlling the inhibitory drive, without altering the timing or pattern of the afferent spike train. Therefore, this NO-mediated suppression of KCC2 can modulate inhibition in one target nucleus (SPN), without influencing inhibitory strength of other target nuclei (MSO, LSO) even though they are each receiving collaterals from the same afferent nucleus (a projection from the medial nucleus of the trapezoid body, MNTB).

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The Depolarizing Action of GABA Controls Early Network Activity in the Developing Hippocampus

Cited by 57 publications

References 83 publications

Calcium-Induced Calcium Release during Action Potential Firing in Developing Inner Hair Cells

Calcium-Induced Calcium Release during Action Potential Firing in Developing Inner Hair Cells

Altered Neuronal and Circuit Excitability in Fragile X Syndrome

Nitric oxide signaling modulates synaptic inhibition in the superior paraolivary nucleus (SPN) via cGMP-dependent suppression of KCC2

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