The h-Current in the Substantia Nigra pars Compacta Neurons: A Re-examination

Gambardella, Cristina; Pignatelli, Angela; Belluzzi, Ottorino

doi:10.1371/journal.pone.0052329

Cited by 15 publications

(14 citation statements)

References 109 publications

(133 reference statements)

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“…As observed in other systems [42], [49] the increase of intracellular levels of cAMP also changes the activation time course of the h-current onset: in experiments conducted in high [K + ] o saline (EC3), we observed adecreasing activation time constant both with forskolin (from 141.75±13.81 to 95.58±17.94, n = 7, P<0.02) and with 8Br-cAMP (from 130.27±26.16 to 103.21±23.48, n = 7, P<0.02).…”

Section: Resultssupporting

confidence: 78%

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The h-Current in Periglomerular Dopaminergic Neurons of the Mouse Olfactory Bulb

et al. 2013

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The properties of the hyperpolarization-activated cation current (Ih) were investigated in rat periglomerular dopaminergic neurons using patch-clamp recordings in thin slices. A reliable identification of single dopaminergic neurons was made possible by use of a transgenic line of mice expressing eGFP under the tyrosine hydroxylase promoter. At 37 °C and minimizing the disturbance of the intracellular milieu with perforated patches, this current shows a midpoint of activation around −82.7 mV, with a significant level of opening already at rest, thereby giving a substantial contribution to the resting potential, and ultimately playing a relevant function in the control of the cell excitability. The blockage of Ih has a profound influence on the spontaneous firing of these neurons, which result as strongly depressed. However the effect is not due to a direct role of the current in the pacemaker process, but to the Ih influence on the resting membrane potential. Ih kinetics is sensitive to the intracellular levels of cAMP, whose increase promotes a shift of the activation curve towards more positive potentials. The direct application of DA and 5-HT neurotransmitters, physiologically released onto bulbar dopaminergic neurons and known to act on metabotropic receptors coupled to the cAMP pathway, do not modifythe Ih amplitude. On the contrary, noradrenaline almost halves the Ih amplitude. Our data indicate that the HCN channels do not participate directly to the pacemaker activity of periglomerular dopaminergic neurons, but influence their resting membrane potential by controlling the excitability profile of these cells, and possibly affecting the processing of sensory information taking place at the entry of the bulbar circuitry.

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Section: Resultssupporting

confidence: 78%

“…1 was solved numerically for t using standard numerical methods [40], [41] solving Eqn. 1 for f(t) = 90 and 10 (the Matlab code used can be found in the Supplementary material of [42]), thereby obtaining t 10 and t 90 , respectively.…”

Section: Resultsmentioning

confidence: 99%

The h-Current in Periglomerular Dopaminergic Neurons of the Mouse Olfactory Bulb

et al. 2013

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“…Temperature did not further depolarize the activation range of I H . In the substantia nigra increasing recording temperature depolarizes the activation range of I H by as much as 15-20 mV (Gambardella et al, 2012). Here we found that recording in 500 M db-cAMP with an elevated temperature (35°C) did not further depolarize the activation range of I H (Fig.…”

Section: Modulating the Voltage-dependent Activation Range Of I Hsupporting

confidence: 48%

“…Third, we used 100 and 500 M db-cAMP, a non-hydrolysable version of cAMP that resists degradation by phosphodiesterases. Fourth, we tested if the activation of I H is further enhanced by increasing recording temperature, as previously reported in the substantia nigra (Gambardella et al, 2012).…”

Section: Enhancing the Activation Of I H By Controlling Camp Concentrmentioning

confidence: 90%

Enhanced Activation of HCN Channels Reduces Excitability and Spike-Timing Regularity in Maturing Vestibular Afferent Neurons

Ventura

Kalluri

2019

J. Neurosci.

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Vestibular ganglion neurons (VGNs) transmit information along parallel neuronal pathways whose signature distinction is variability in spike-timing; some fire at regular intervals while others fire at irregular intervals. The mechanisms driving timing differences are not fully understood but two opposing (but not mutually exclusive) hypotheses have emerged. In the first, regular-spiking is inversely correlated to the density of low-voltage-gated potassium currents (I KL ). In the second, regular spiking is directly correlated to the density of hyperpolarization-activated cyclic nucleotide-sensitive currents (I H ). Supporting the idea that variations in ion channel composition shape spike-timing, VGNs from the first postnatal week respond to synaptic-noise-like current injections with irregular-firing patterns if they have I KL and with more regular firing patterns if they do not. However, in vitro firing patterns are not as regular as those in vivo. Here we considered whether highly-regular spiking requires I H currents and whether this dependence emerges later in development after channel expression matures. We recorded from rat VGN somata of either sex aged postnatal day (P)9 -P21. Counter to expectation, in vitro firing patterns were less diverse, more transient-spiking, and more irregular at older ages than at younger ages. Resting potentials hyperpolarized and resting conductance increased, consistent with developmental upregulation of I KL . Activation of I H (by increasing intracellular cAMP) increased spike rates but not spike-timing regularity. In a model, we found that activating I H counter-intuitively suppressed regularity by recruiting I KL . Developmental upregulation in I KL appears to overwhelm I H . These results counter previous hypotheses about how I H shapes vestibular afferent responses. Significance StatementVestibular sensory information is conveyed on parallel neuronal pathways with irregularly-firing neurons encoding information using a temporal code and regularly-firing neurons using a rate code. This is a striking example of spike-timing statistics influencing information coding. Previous studies from immature vestibular ganglion neurons (VGNs) identified hyperpolarizationactivated mixed cationic currents (I H ) as driving highly-regular spiking and proposed that this influence grows with the current during maturation. We found that I H becomes less influential, likely because maturing VGNs also acquire low-voltage-gated potassium currents (I KL ), whose inhibitory influence opposes I H . Because efferent activity can partly close I KL , VGN firing patterns may become more receptive to extrinsic control. Spike-timing regularity likely relies on dynamic ion channel properties and complementary specializations in synaptic connectivity.

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“…I h is an inward (depolarizing) Na ϩ /K ϩ current carried by hyperpolarization-activated cyclic nucleotide gated (HCN) channels. Consistent with evidence that cooling inhibits I h (11,37,40), we found cooling eliminated the depolarizing voltage "sag" caused by activation of I h during negative current injection (47). Inhibition of an excitatory membrane current associated with pacemaking is seemingly at odds with our findings that LC neurons intrinsically increase spontaneous discharge at cold temperatures.…”

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confidence: 87%

Activation state of the hyperpolarization-activated current modulates temperature-sensitivity of firing in locus coeruleus neurons from bullfrogs

Santin

Hartzler

2015

American Journal of Physiology-Regulatory, Integrative and Comp

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-Locus coeruleus neurons of anuran amphibians contribute to breathing control and have spontaneous firing frequencies that, paradoxically, increase with cooling. We previously showed that cooling inhibits a depolarizing membrane current, the hyperpolarization-activated current (Ih) in locus coeruleus neurons from bullfrogs, Lithobates catesbeianus (Santin JM, Watters KC, Putnam RW, Hartzler LK. Am J Physiol Regul Integr Comp Physiol 305: R1451-R1464, 2013). This suggests an unlikely role for I h in generating cold activation, but led us to hypothesize that inhibition of I h by cooling functions as a physiological brake to limit the cold-activated response. Using whole cell electrophysiology in brain slices, we employed 2 mM Cs ϩ (an Ih antagonist) to isolate the role of Ih in spontaneous firing and cold activation in neurons recorded with either control or I h agonist (cyclic AMP)-containing artificial intracellular fluid. I h did not contribute to the membrane potential (V m) and spontaneous firing at 20°C. Although voltage-clamp analysis confirmed that cooling inhibits I h, its lack of involvement in setting baseline firing and V m precluded its ability to regulate cold activation as hypothesized. In contrast, neurons dialyzed with cAMP exhibited greater baseline firing frequencies at 20°C due to I h activation. Our hypothesis was supported when the starting level of I h was enhanced by elevating cAMP because cold activation was converted to more ordinary cold inhibition. These findings indicate that situations leading to enhancement of I h facilitate firing at 20°C, yet the hyperpolarization associated with inhibiting a depolarizing cation current by cooling blunts the net V m response to cooling to oppose normal cold-depolarizing factors. This suggests that the influence of I h activation state on neuronal firing varies in the poikilothermic neuronal environment.temperature; Q10; neuronal excitability; hyperpolarization-activated current; respiratory control THE AMERICAN BULLFROG, Lithobates catesbeianus, has a broad geographical distribution within North America and undergoes rapid and variable temperature changes throughout a single day (21, 49). Owing to the temperature sensitivity of neurophysiological mechanisms, changes in temperature pose a challenge to regulating neurally controlled behaviors, like breathing, in the bullfrog and other poikilothermic animals. Despite rate increases of neurally controlled, rhythmic behaviors typically associated with temperature (41), aspects of the respiratory pattern are maintained across temperatures in amphibians and other ectothermic vertebrates. Specifically, breathing frequency has low temperature dependence (Q 10 ϳ 1.7) during changes at higher temperatures (2, 42), and tidal volume (i.e., the volume of air consumed in a breath) is insensitive to variations in temperature (27,51). Consistent with these observations in vivo, respiratory-related cranial nerve activity of the isolated bullfrog brain stem in vitro maintains burst frequency across higher temperatu...

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The h-Current in the Substantia Nigra pars Compacta Neurons: A Re-examination

Cited by 15 publications

References 109 publications

The h-Current in Periglomerular Dopaminergic Neurons of the Mouse Olfactory Bulb

The h-Current in Periglomerular Dopaminergic Neurons of the Mouse Olfactory Bulb

Enhanced Activation of HCN Channels Reduces Excitability and Spike-Timing Regularity in Maturing Vestibular Afferent Neurons

Activation state of the hyperpolarization-activated current modulates temperature-sensitivity of firing in locus coeruleus neurons from bullfrogs

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