Two forms of electrical resonance at theta frequencies, generated by M‐current, h‐current and persistent Na<sup>+</sup>current in rat hippocampal pyramidal cells

Hu, Hua; Vervaeke, Koen; Storm, Johan F.

doi:10.1113/jphysiol.2002.029249

Cited by 399 publications

(618 citation statements)

References 82 publications

(203 reference statements)

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“…KCNQ channels contribute to the neuronal resting membrane potentials (16), hippocampal theta oscillation (17,18), spike frequency adaptation (16,(18)(19)(20), spike after depolarization (16,21), and after hyperpolarization (18,20). Consistent with reports of the ability of KCNQ channels to modulate motor axon excitability (9,22) and transmitter release (23), KCNQ2 and KCNQ3 proteins have been detected in axons (5,6,24,25), the axonal initial segment (AIS) and nodes of Ranvier (26,27).…”

supporting

confidence: 60%

Polarized axonal surface expression of neuronal KCNQ channels is mediated by multiple signals in the KCNQ2 and KCNQ3 C-terminal domains

Chung

Jan

2006

Proc. Natl. Acad. Sci. U.S.A.

178

214

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The M channels, important regulators of neuronal excitability, are voltage-gated potassium channels composed of KCNQ2-5 subunits. Mutations in KCNQ2 and KCNQ3 cause benign familial neonatal convulsions (BFNC), dominantly inherited epilepsy and myokymia. Crucial for their functions in controlling neuronal excitability, the M channels must be placed at specific regions of the neuronal membrane. However, the precise distribution of surface KCNQ channels is not known. Here, we show that KCNQ2͞KCNQ3 channels are preferentially localized to the surface of axons both at the axonal initial segment and more distally. Whereas axonal initial segment targeting of surface KCNQ channels is mediated by ankyrin-G binding motifs of KCNQ2 and KCNQ3, sequences mediating targeting to more distal portion of the axon reside in the membrane proximal and A domains of the KCNQ2 C-terminal tail. We further show that several BFNC mutations of KCNQ2 and KCNQ3 disrupt surface expression or polarized surface distribution of KCNQ channels, thereby revealing impaired targeting of KCNQ channels to axonal surfaces as a BFNC etiology.axon initial segment ͉ axon targeting ͉ epilepsy ͉ KCNQ potassium channel N euronal KCNQ channels, voltage-dependent potassium channels that activate slowly but show no inactivation, correspond to the M channels that exert crucial influence over neuronal excitability (1). Inhibition of M channels by muscarinic agonist (hence the name) and other neurotransmitters enhances action potential firing in central and autonomic neurons (2). M channels are mostly heterotetramers composed of KCNQ2 and KCNQ3 (3,4). The overlapping expression patterns of KCNQ2 and KCNQ3 include brain areas implicated in seizure development, such as hippocampus, neocortex, and thalamus (3, 5, 6). The critical involvement of KCNQ channels in controlling neuronal excitability is underscored further by the fact that benign familial neonatal convulsions (BFNC) mutations in KCNQ2 and KCNQ3 cause epilepsy (7,8) and myokymia (9). Consistently, retigabine, a potent KCNQ channel opener (10) can suppress seizures in a number of animal models (11-13) and attenuate neuropathic pain (14, 15), whereas linopirdine and XE991, developed as ''cognitive enhancer'' drugs for treatment of Alzheimer disease and other memory disorders, are potent blockers of KCNQ channels (10).KCNQ channels contribute to the neuronal resting membrane potentials (16), hippocampal theta oscillation (17, 18), spike frequency adaptation (16,(18)(19)(20), spike after depolarization (16, 21), and after hyperpolarization (18,20). Consistent with reports of the ability of KCNQ channels to modulate motor axon excitability (9, 22) and transmitter release (23), KCNQ2 and KCNQ3 proteins have been detected in axons (5,6,24,25), the axonal initial segment (AIS) and nodes of Ranvier (26,27). It remains possible, however, that the neuronal soma and dendrites express functional KCNQ channels, given the transmitter modulation of KCNQ channels (2) and strong somatodendritic KCNQ2 and KCNQ3 immunoreactivi...

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supporting

confidence: 60%

Polarized axonal surface expression of neuronal KCNQ channels is mediated by multiple signals in the KCNQ2 and KCNQ3 C-terminal domains

Chung

Jan

2006

Proc. Natl. Acad. Sci. U.S.A.

178

214

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“…Persistent sodium current is known to amplify subthreshold oscillations [69] and increases neural excitability of DA neurons by contributing to spontaneous depolarization in between the spikes [25]. Consistent with experimental observations, the subthreshold sodium current population receiving the tonic synaptic inputs.…”

Section: The Role Of the Subthreshold Sodium Currentsupporting

confidence: 67%

Dopamine neurons change the type of excitability in response to stimuli

Morozova

Zakharov²,

Gutkin

et al. 2016

Preprint

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The dynamics of neuronal excitability determine the neuron's response to stimuli, its synchronization and resonance properties and, ultimately, the computations it performs in the brain. We investigated the dynamical mechanisms underlying the excitability type of dopamine (DA) neurons, using a conductance-based biophysical model, and its regulation by intrinsic and synaptic currents. Calibrating the model to reproduce low frequency tonic firing results in N-methyl-D-aspartate (NMDA) excitation balanced by γ-Aminobutyric acid (GABA)-mediated inhibition and leads to type I excitable behavior characterized by a continuous decrease in firing frequency in response to hyperpolarizing currents. Furthermore, we analyzed how excitability type of the DA neuron model is influenced by changes in the intrinsic current composition. A subthreshold sodium current is necessary for a continuous frequency decrease during application of a negative current, and the low-frequency "balanced" state during simultaneous activation of NMDA and GABA receptors. Blocking this current switches the neuron to type II characterized by the abrupt onset of repetitive firing. Enhancing the anomalous rectifier Ih current also switches the excitability to type II. Key characteristics of synaptic conductances that may be observed in vivo also change the type of excitability: a depolarized γ-Aminobutyric acid receptor (GABAR) reversal potential or coactivation of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors (AMPARs) leads to an abrupt frequency drop to zero, which is typical for type II excitability. Coactivation of N-methyl-D-aspartate receptors (NMDARs) together with AMPARs and GABARs shifts the type I/II boundary toward more hyperpolarized GABAR reversal potentials. To better understand how altering each of the aforementioned currents leads to changes in excitability profile of DA neuron, we provide a thorough dynamical analysis. Collectively, these results imply that type I excitability in dopamine neurons might be important for low firing rates and fine-tuning basal dopamine levels, while switching excitability to type II during NMDAR and AMPAR activation may facilitate a transient increase in dopamine concentration, as type II neurons are more amenable to synchronization by mutual excitation. Author SummaryDopamine neurons play a central role in guiding motivated behaviors. However, complete understanding of computations these neurons perform to encode rewarding and salient stimuli is still forthcoming. Network connectivity influences neural responses to stimuli, but so do intrinsic excitability properties of individual neurons, as such properties define synchronization qualities and neural coding strategy. We investigated the excitability type of the DA neuron and found that, depending on the synaptic and intrinsic current composition, DA neurons can switch from type I to type II excitability. In short, without synaptic inputs or under balanced excitatory and inhibitory inputs DA neurons exhibits type I excitability, w...

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“…One possible explanation for the speed effect on the oscillation frequency of place cells is that the frequency is controlled by the activation of voltage-dependent intrinsic mechanisms that support oscillations in single pyramidal cells (5,8,9,13,(30)(31)(32)(33)(34). However, this individuated oscillation cannot account for several experimental observations (7,24,35).…”

Section: Speed-dependent Oscillation Of Place Cells Can Keep the Spikmentioning

confidence: 79%

Hippocampal place cell assemblies are speed-controlled oscillators

Geisler

Robbe

Zugaro

et al. 2007

Proc. Natl. Acad. Sci. U.S.A.

253

321

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The phase of spikes of hippocampal pyramidal cells relative to the local field oscillation shifts forward (''phase precession'') over a full cycle as the animal crosses the cell's receptive field (''place field''). The linear relationship between the phase of the spikes and the travel distance within the place field is independent of the animal's running speed. This invariance of the phase-distance relationship is likely to be important for coordinated activity of hippocampal cells and space coding, yet the mechanism responsible for it is not known. Here we show that at faster running speeds place cells are active for fewer cycles but oscillate at a higher frequency and emit more spikes per cycle. As a result, the phase shift of spikes from cycle to cycle (i.e., temporal precession slope) is faster, yet spatial-phase precession stays unchanged. Interneurons can also show transient-phase precession and contribute to the formation of coherently precessing assemblies. We hypothesize that the speed-correlated acceleration of place cell assembly oscillation is responsible for the phase-distance invariance of hippocampal place cells.cell assembly ͉ interneurons ͉ phase locking ͉ phase precession ͉ oscillations W hile animals navigate in an environment, the hippocampal local field potential (LFP) is characterized by a highly regular oscillation (8-10 Hz). Principal cells in the hippocampus show place-specific firing by two criteria. First, the firing is tuned to a particular location (''place field''), showing a bellshaped tuning curve centered around its preferred location (1). Second, the timing of spikes within subsequent cycles systematically shifts forward (''phase precession''), Ϸ1 full cycle in total, as the rat runs through the place field of the neuron (2, 3) (see also Fig. 1 A and B). Both the firing rate and discharge phase within a cycle are correlated with the rat's position. However, how the rate change and -phase precession of spikes are related is poorly understood. The available experiments support both a rate-phase interdependence (4-6) and independence (7).Several explanations for the place-phase relationship were put forward (4)(5)(6)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18). To confront these models, we examined the relationship among running speed, oscillation frequency of place cells and LFP , and timing of spikes within the cycle. We show that principal cells oscillate at a frequency faster than the simultaneously recorded LFP oscillation, and that this oscillation frequency depends on the rat's running speed. Together with the place-and speed-dependent oscillation frequencies of interneurons, the findings support the hypothesis that place coding results from coordinated network activity. We propose that the locomotion speed-dependent oscillation of place cell assemblies may underlie the mechanisms responsible for distance encoding in the hippocampus. ResultsWe recorded the firing patterns of pyramidal cells, interneurons, and the LFP from the CA1 pyramidal layer of rats as they ran on a U-shap...

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Two forms of electrical resonance at theta frequencies, generated by M‐current, h‐current and persistent Na⁺current in rat hippocampal pyramidal cells

Cited by 399 publications

References 82 publications

Polarized axonal surface expression of neuronal KCNQ channels is mediated by multiple signals in the KCNQ2 and KCNQ3 C-terminal domains

Polarized axonal surface expression of neuronal KCNQ channels is mediated by multiple signals in the KCNQ2 and KCNQ3 C-terminal domains

Dopamine neurons change the type of excitability in response to stimuli

Hippocampal place cell assemblies are speed-controlled oscillators

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Two forms of electrical resonance at theta frequencies, generated by M‐current, h‐current and persistent Na+current in rat hippocampal pyramidal cells

Cited by 399 publications

References 82 publications

Polarized axonal surface expression of neuronal KCNQ channels is mediated by multiple signals in the KCNQ2 and KCNQ3 C-terminal domains

Polarized axonal surface expression of neuronal KCNQ channels is mediated by multiple signals in the KCNQ2 and KCNQ3 C-terminal domains

Dopamine neurons change the type of excitability in response to stimuli

Hippocampal place cell assemblies are speed-controlled oscillators

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Product

Resources

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Two forms of electrical resonance at theta frequencies, generated by M‐current, h‐current and persistent Na⁺current in rat hippocampal pyramidal cells