The interplay of seven subthreshold conductances controls the resting membrane potential and the oscillatory behavior of thalamocortical neurons

Amarillo, Yimy; Zagha, Edward; Mato, Germán; Rudy, Bernardo; Nadal, Marcela S.

doi:10.1152/jn.00647.2013

Cited by 41 publications

(91 citation statements)

References 71 publications

(101 reference statements)

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“…; Amarillo et al . ) and its gating has long been considered crucial for facilitating transitions between hyperpolarized potentials where burst firing predominates and more depolarized modes of tonic firing. It is also considered crucial to the emergence of rhythmic activities in the thalamus (McCormick & Pape, ; Pape, ).…”

Section: Discussionmentioning

confidence: 99%

In vitro characterization of cell‐level neurophysiological diversity in the rostral nucleus reuniens of adult mice

Walsh

Brown

Randall

2017

The Journal of Physiology

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The nucleus reuniens (Re) is the largest of the midline thalamic nuclei. We have performed a detailed neurophysiological characterization of neurons in the rostral Re of brain slices prepared from adult male mice. At resting potential (-63.7 ± 0.6 mV), ∼90% of Re neurons fired action potentials, typically continuously at ∼8 Hz. Although Re neurons experience a significant spontaneous barrage of fast, amino-acid-mediate synaptic transmission, this was not predominantly responsible for spontaneous spiking because firing persisted in the presence of glutamate and GABA receptor antagonists. With resting potential preset to -80 mV, -20 pA current injections revealed a mean input resistance of 615 MΩ and a mean time constant of 38 ms. Following cessation of this stimulus, a significant rebound potential was seen that was sometimes sufficiently large to trigger a short burst of very high frequency (100-300 Hz) firing. In most cells, short (2 ms), strong (2 nA) current injections elicited a single spike followed by a large afterdepolarizing potential which, when suprathreshold, generated high-frequency spiking. Similarly, in the majority of cells preset at -80 mV, 500 ms depolarizing current injections to cells led to a brief initial burst of very high-frequency firing, although this was lost when cells were preset at -72 mV. Biophysical and pharmacological experiments indicate a prominent role for T-type Ca channels in the high-frequency bursting of Re neurons. Finally, we describe a novel form of activity-dependent intrinsic plasticity that persistently eliminates the burst firing potential of Re neurons.

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Section: Discussionmentioning

confidence: 99%

In vitro characterization of cell‐level neurophysiological diversity in the rostral nucleus reuniens of adult mice

Walsh

Brown

Randall

2017

The Journal of Physiology

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“…One of the most extensive studies of the resting potentials of thalamocortical neurons concluded that the interplay of seven conductances controls the resting potential (Amarillo et al, 2014). Claims have been made about conductances, especially of g h , that they are determinants of the resting potential but those claims are usually based on short-term changes in the resting potential after conductances are acutely blocked (Pape, 1996).…”

Section: Discussionmentioning

confidence: 99%

Genetic perturbations suggest a role of the resting potential in regulating the expression of the ion channels of the KCNA and HCN families in octopus cells of the ventral cochlear nucleus

Cao

Oertel

2017

Hearing Research

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Low-voltage-activated K+ (gKL) and hyperpolarization-activated mixed cation conductances (gh) mediate currents, IKL and Ih, through channels of the Kv1 (KCNA) and HCN families respectively and give auditory neurons the temporal precision required for signaling information about the onset, fine structure, and time of arrival of sounds. Being partially activated at rest, gKL and gh contribute to the resting potential and shape responses to even small subthreshold synaptic currents. Resting gKL and gh also affect the coupling of somatic depolarization with the generation of action potentials. To learn how these important conductances are regulated we have investigated how genetic perturbations affect their expression in octopus cells of the ventral cochlear nucleus (VCN). We report five new findings: First, the magnitude of gh and gKL varied over more than two-fold between wild type strains of mice. Second, average resting potentials are not different in different strains of mice even in the face of large differences in average gKL and gh. Third, IKL has two components, one being α-dendrotoxin (α-DTX)-sensitive and partially inactivating and the other being α-DTX-insensitive, tetraethylammonium (TEA)-sensitive, and non-inactivating. Fourth, the loss of Kv1.1 results in diminution of the α-DTX-sensitive IKL, and compensatory increased expression of an α-DTX-insensitive, tetraethylammonium (TEA)-sensitive IKL. Fifth, Ih and IKL are balanced at the resting potential in all wild type and mutant octopus cells even when resting potentials vary in individual cells over nearly 10 mV, indicating that the resting potential influences the expression of gh and gKL. The independence of resting potentials on gKL and gh shows that gKL and gh do not, over days or weeks, determine the resting potential but rather that the resting potential plays a role in regulating the magnitude of either or both gKL and gh.

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“…Likewise, I NaP appears to play a critical role in the control of spontaneous repetitive firing and T-type calcium channel-mediated burst firing of AVPV/PeN Kiss1 neurons. The function of I NaP in different cells is determined by its interaction with other subthreshold conductances including I T , I h and I Kir (20,32,33). For example, hippocampal CA1 pyramidal neurons are normally quiescent, but they express a robust I NaP and fire spontaneously when depolarized by muscarinic agonists that bring the membrane potential into the activation voltage range of I NaP (15).…”

Section: Discussionmentioning

confidence: 99%

“…Indeed, we found that blockade of I NaP by riluzole attenuated spontaneous repetitive firing (ie, Figure 3B). Furthermore, Amarillo and colleagues (20) predicted that I NaP in combination with I T will enhance burst firing in thalamocortical neurons, due to the fact that the activation of I T depolarizes the membrane potential into the activation range of I NaP , which boosts the generation of action potentials during a burst firing event. As predicted, riluzole significantly diminished the number of spikes during rebound burst firing of AVPV/PeN Kiss1 neurons (ie, Figure 4).…”

Section: Discussionmentioning

confidence: 99%

“…Therefore, I NaP shapes repetitive firing, generates rhythmicity and amplifies excitatory postsynaptic potentials (EPSPs) (12). I NaP modulates pacemaking activity in numerous CNS neurons including cerebellar Purkinje neurons (13,14), CA1 pyramidal neurons (15), ventral tegmental dopamine neurons (16), hypothalamic suprachiasmatic neurons (17), tuberomammilary histamine neurons (18) and GnRH neurons (19), all of which depend on the interplay between I NaP, I T and I h (20). Also, neurotransmitters that affect any of these conductances greatly facilitate burst firing activity.…”

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confidence: 99%

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17β-Estradiol Increases Persistent Na+ Current and Excitability of AVPV/PeN Kiss1 Neurons in Female Mice

Zhang

Bosch

Qiu

et al. 2015

Molecular Endocrinology

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In vitro slice studies have revealed that there are significant differences in the spontaneous firing activity between anteroventral periventricular/periventricular preoptic nucleus (AVPV/PeN) and arcuate nucleus (ARC) kisspeptin (Kiss1) neurons in females. Although both populations express similar endogenous conductances, we have discovered that AVPV/PeN Kiss1 neurons express a subthreshold, persistent sodium current (INaP) that dramatically alters their firing activity. Based on whole-cell recording of Kiss1-Cre-green fluorescent protein (GFP) neurons, INaP was 4-fold greater in AVPV/PeN vs ARC Kiss1 neurons. An LH surge-producing dose of 17β-estradiol (E2) that increased Kiss1 mRNA expression in the AVPV/PeN, also augmented INaP in AVPV/PeN neurons by 2-fold. Because the activation threshold for INaP was close to the resting membrane potential (RMP) of AVPV/PeN Kiss1 neurons (-54 mV), it rendered them much more excitable and spontaneously active vs ARC Kiss1 neurons (RMP = -66 mV). Single-cell RT-PCR revealed that AVPV/PeN Kiss1 neurons expressed the requisite sodium channel α-subunit transcripts, NaV1.1, NaV1.2, and NaV1.6 and β subunits, β2 and β4. Importantly, NaV1.1α and -β2 transcripts in AVPV/PeN, but not ARC, were up-regulated 2- to 3-fold by a surge-producing dose of E2, similar to the transient calcium current channel subunit Cav3.1. The transient calcium current collaborates with INaP to generate burst firing, and selective blockade of INaP by riluzole significantly attenuated rebound burst firing and spontaneous activity. Therefore, INaP appears to play a prominent role in AVPV/PeN Kiss1 neurons to generate spontaneous, repetitive burst firing, which is required for the high-frequency-stimulated release of kisspeptin for exciting GnRH neurons and potentially generating the GnRH surge.

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The interplay of seven subthreshold conductances controls the resting membrane potential and the oscillatory behavior of thalamocortical neurons

Cited by 41 publications

References 71 publications

In vitro characterization of cell‐level neurophysiological diversity in the rostral nucleus reuniens of adult mice

In vitro characterization of cell‐level neurophysiological diversity in the rostral nucleus reuniens of adult mice

Genetic perturbations suggest a role of the resting potential in regulating the expression of the ion channels of the KCNA and HCN families in octopus cells of the ventral cochlear nucleus

17β-Estradiol Increases Persistent Na+ Current and Excitability of AVPV/PeN Kiss1 Neurons in Female Mice

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