scholarly journals Profound Alterations in the Intrinsic Excitability of Cerebellar Purkinje Neurons Following Neurotoxin 3-Acetylpyridine (3-AP)-Induced Ataxia in Rat: New Insights Into the Role of Small Conductance K+ Channels

2011 ◽  
pp. 355-365 ◽  
Author(s):  
M. KAFFASHIAN ◽  
M. SHABANI ◽  
I. GOUDARZI ◽  
G. BEHZADI ◽  
A. ZALI ◽  
...  
Keyword(s):  
Neuronal Excitability ◽  
Input Resistance ◽  
Firing Frequency ◽  
Discharge Frequency ◽  
Sk Channels ◽  
Intrinsic Properties ◽  
K Channels ◽  
Initial Discharge ◽  
Small Conductance

Alterations in the intrinsic properties of Purkinje cells (PCs) may contribute to the abnormal motor performance observed in ataxic rats. To investigate whether such changes in the intrinsic neuronal excitability could be attributed to the role of Ca2+-activated K+ channels (KCa), whole cell current clamp recordings were made from PCs in cerebellar slices of control and ataxic rats. 3-AP induced profound alterations in the intrinsic properties of PCs, as evidenced by a significant increase in both the membrane input resistance and the initial discharge frequency, along with the disruption of the firing regularity. In control PCs, the blockade of small conductance KCa channels by UCL1684 resulted in a significant increase in the membrane input resistance, action potential (AP) half-width, time to peak of the AP and initial discharge frequency. SK channel blockade also significantly decreased the neuronal discharge regularity, the peak amplitude of the AP, the amplitude of the after- hyperpolarization and the spike frequency adaptation ratio. In contrast, in ataxic rats, both the firing regularity and the initial firing frequency were significantly increased by the blockade of SK channels. In conclusion, ataxia may arise from alterations in the functional contribution of SK channels, to the intrinsic properties of PCs.

Abstract P201: Negative Regulation Of PVN Pre-sympathetic Neuronal Activity By Resident Microglia

Hypertension ◽  
2021 ◽  
Vol 78 (Suppl_1) ◽  
Author(s):  
Peng Shi ◽  
Yunfan Lin ◽  
Qianqian Bi ◽  
Guo Cheng ◽  
Xiao Shen
Keyword(s):  
Neuronal Excitability ◽  
Sympathetic Neurons ◽  
Potassium Currents ◽  
Firing Frequency ◽  
Electrophysiological Recording ◽  
Recombinant Peptide ◽  
Regulatory Circuits ◽  
Brain Parenchymal ◽  
Parenchymal Cells

Hypothalamic paraventricular nucleus (PVN) is a critical integrating region in controlling peripheral sympathetic tonicity. While the vast studies have unraveled the regulatory circuits affecting PVN pre-sympathetic neurons, local factors for maintaining the homeostasis of neuronal excitability are barely understood. In the present study we investigated the role of microglia, the primary resident immune cells of the CNS, in this context. By electrophysiological recording, we found that loss of resident microglia induced an increased firing frequency and attenuated outward potassium currents in the PVN pre-sympathetic neurons, tachycardia and impaired heart rate variability. Combining the transcriptomics analysis of the PVN microglia, we identified a releasable factor, which was dominantly expressed in microglia compared to other brain parenchymal cells. ICV infusion of the recombinant peptide restored potassium currents in the PVN pre-sympathetic neurons and autonomic function in microglia-depleted mice. In summary, our results provided a novel intrinsic regulatory mechanism by which microglia suppress neuronal over excitation in physiological condition.

scholarly journals Adult spinal V2a interneurons show increased excitability and serotonin-dependent bistability

2015 ◽  
Vol 113 (4) ◽  
pp. 1124-1134 ◽  
Author(s):  
Andreas Husch ◽  
Shelby B. Dietz ◽  
Diana N. Hong ◽  
Ronald M. Harris-Warrick
Keyword(s):  
Postnatal Development ◽  
Input Resistance ◽  
Firing Frequency ◽  
Intrinsic Properties ◽  
Spinal Interneurons ◽  
Age Dependent ◽  
Immature Form ◽  
Almost All ◽  
A Current ◽  
Serotonergic Modulation

In mice, most studies of the organization of the spinal central pattern generator (CPG) for locomotion, and its component neuron classes, have been performed on neonatal [postnatal day (P)2-P4] animals. While the neonatal spinal cord can generate a basic locomotor pattern, it is often argued that the CPG network is in an immature form whose detailed properties mature with postnatal development. Here, we compare intrinsic properties and serotonergic modulation of the V2a class of excitatory spinal interneurons in behaviorally mature (older than P43) mice to those in neonatal mice. Using perforated patch recordings from genetically tagged V2a interneurons, we revealed an age-dependent increase in excitability. The input resistance increased, the rheobase values decreased, and the relation between injected current and firing frequency ( F/ I plot) showed higher excitability in the adult neurons, with almost all neurons firing tonically during a current step. The adult action potential (AP) properties became narrower and taller, and the AP threshold hyperpolarized. While in neonates the AP afterhyperpolarization was monophasic, most adult V2a interneurons showed a biphasic afterhyperpolarization. Serotonin increased excitability and depolarized most neonatal and adult V2a interneurons. However, in ∼30% of adult V2a interneurons, serotonin additionally elicited spontaneous intrinsic membrane potential bistability, resulting in alternations between hyperpolarized and depolarized states with a dramatically decreased membrane input resistance and facilitation of evoked plateau potentials. This was never seen in younger animals. Our findings indicate a significant postnatal development of the properties of locomotor-related V2a interneurons, which could alter their interpretation of synaptic inputs in the locomotor CPG.

scholarly journals Intrinsic properties of the sodium sensor neurons in the rat median preoptic nucleus

2012 ◽  
Vol 303 (8) ◽  
pp. R834-R842 ◽  
Author(s):  
Aurore N. Voisin ◽  
Guy Drolet ◽  
Didier Mouginot
Keyword(s):  
Electrical Properties ◽  
Brain Slices ◽  
Firing Frequency ◽  
The Body ◽  
Neural Population ◽  
Preoptic Nucleus ◽  
Intrinsic Properties ◽  
Median Preoptic Nucleus ◽  
Current Steps

The essential role of the median preoptic nucleus (MnPO) in the integration of chemosensory information associated with the hydromineral state of the rat relies on the presence of a unique population of sodium (Na+) sensor neurons. Little is known about the intrinsic properties of these neurons; therefore, we used whole cell recordings in acute brain slices to determine the electrical fingerprints of this specific neural population of rat MnPO. The data collected from a large sample of neurons (115) indicated that the Na+ sensor neurons represent a majority of the MnPO neurons in situ (83%). These neurons displayed great diversity in both firing patterns induced by transient depolarizing current steps and rectifying properties activated by hyperpolarizing current steps. This diversity of electrical properties was also present in non-Na+ sensor neurons. Subpopulations of Na+ sensor neurons could be distinguished, however, from the non-Na+ sensor neurons. The firing frequency was higher in Na+ sensor neurons, showing irregular spike discharges, and the amplitude of the time-dependent rectification was weaker in the Na+ sensor neurons than in non-Na+ sensor neurons. The diversity among the electrical properties of the MnPO neurons contrasts with the relative function homogeneity (Na+ sensing). However, this diversity might be correlated with a variety of direct synaptic connections linking the MnPO to different brain areas involved in various aspects of the restoration and conservation of the body fluid homeostasis.

scholarly journals Alterations in the intrinsic properties of striatal cholinergic interneurons after dopamine lesion and chronic L-DOPA

eLife ◽  
2020 ◽  
Vol 9 ◽  
Author(s):  
Se Joon Choi ◽  
Thong C Ma ◽  
Yunmin Ding ◽  
Timothy Cheung ◽  
Neal Joshi ◽  
...  
Keyword(s):  
Normal Activity ◽  
Sk Channels ◽  
Intrinsic Properties ◽  
Therapeutic Approaches ◽  
Physiological Basis ◽  
Cholinergic Interneurons ◽  
Pharmacological Blockade ◽  
Cholinergic Interneuron ◽  
Spontaneous Firing Rate ◽  
Small Conductance

Changes in striatal cholinergic interneuron (ChI) activity are thought to contribute to Parkinson’s disease pathophysiology and dyskinesia from chronic L-3,4-dihydroxyphenylalanine (L-DOPA) treatment, but the physiological basis of these changes is unknown. We find that dopamine lesion decreases the spontaneous firing rate of ChIs, whereas chronic treatment with L-DOPA of lesioned mice increases baseline ChI firing rates to levels beyond normal activity. The effect of dopamine loss on ChIs was due to decreased currents of both hyperpolarization-activated cyclic nucleotide-gated (HCN) and small conductance calcium-activated potassium (SK) channels. L-DOPA reinstatement of dopamine normalized HCN activity, but SK current remained depressed. Pharmacological blockade of HCN and SK activities mimicked changes in firing, confirming that these channels are responsible for the molecular adaptation of ChIs to dopamine loss and chronic L-DOPA treatment. These findings suggest that targeting ChIs with channel-specific modulators may provide therapeutic approaches for alleviating L-DOPA-induced dyskinesia in PD patients.

Learning-Induced Reversal of the Effect of Noradrenalin on the Postburst AHP

2006 ◽  
Vol 96 (4) ◽  
pp. 1728-1733 ◽  
Author(s):  
Inbar Brosh ◽  
Kobi Rosenblum ◽  
Edi Barkai
Keyword(s):  
Potassium Current ◽  
Neuronal Excitability ◽  
Pyramidal Neurons ◽  
Piriform Cortex ◽  
Sk Channels ◽  
Similar Extent ◽  
Protein Expression Level ◽  
Calcium Dependent ◽  
The Difference ◽  
Small Conductance

Pyramidal neurons in the piriform cortex from olfactory-discrimination–trained rats have reduced postburst afterhyperpolarization (AHP), for 3 days after learning, and are thus more excitable during this period. Such AHP reduction is caused by decreased conductance of one or more of the calcium-dependent potassium currents, IAHP and s IAHP, that mediate the medium and slow AHPs. In this study, we examined which potassium current is reduced by learning and how the effect of noradrenalin (NE) on neuronal excitability is modified by such reduction. The small conductance (SK) channels inhibitor, apamin, that selectively blocks IAHP, reduced the AHP in neurons from trained, naïve, and pseudotrained rats to a similar extent, thus maintaining the difference in AHP amplitude between neurons from trained rats and controls. In addition, the protein expression level of the SK1, SK2, and SK3 channels was also similar in all groups. NE, which was shown to enhance IAHP while suppressing S IAHP, reduced the AHP in neurons from controls but enhanced the AHP in neurons from trained rats. Our data show that learning-induced enhancement of neuronal excitability is not the result of reduction in the IAHP current. Thus it is probably mediated by reduction in conductance of the other calcium-dependent potassium current, s IAHP. Consequently, the effect of NE on neuronal excitability is reversed. We propose that the change in the effect of NE after learning may act to counterbalance learning-induced hyperexcitability and preserve the piriform cortex ability to subserve olfactory learning.

scholarly journals Autoactivity of A5 neurons: role of subthreshold oscillations and persistent Na+current

1997 ◽  
Vol 273 (5) ◽  
pp. H2280-H2289 ◽  
Author(s):  
Donghai Huangfu ◽  
Patrice G. Guyenet
Keyword(s):  
Membrane Potential ◽  
Discharge Rate ◽  
Input Resistance ◽  
Frequency Component ◽  
Inward Rectification ◽  
Intrinsic Properties ◽  
Potential Oscillations ◽  
Subthreshold Oscillations

A5 noradrenergic neurons play a key role in autonomic regulation, nociception, and respiration. The purpose of the present experiments was to characterize some of the intrinsic properties of A5 cells in vitro. Whole cell recordings were obtained from 85 spinally projecting neurons of the ventrolateral pons of neonate rats. Immunohistochemistry showed that 60% of the ventrolateral pontine cells were noradrenergic. Eighty percent of A5 neurons were spontaneously active (0.1–5.5 spikes/s). Their discharge rate was unchanged by a mixture of synaptic blockers that eliminated postsynaptic potentials (PSPs). The nonnoradrenergic cells could not be distinguished from A5 cells on the basis of discharge rate, action potential duration, inward rectification, input resistance, or accommodation. A5 cells displayed subthreshold irregular oscillations of the membrane potential (main frequency component 0.5–2 Hz). These oscillations were unchanged in the presence of low external Ca2+-high Mg2+ and were very reduced by hyperpolarizing the cells below −65 mV. The oscillations were partially attenuated by 1 μM tetrodotoxin (TTX) and were eliminated by reducing external Na+ (27 mM). Stepping the membrane potential from −65 to −50 mV for 200 ms revealed the presence of a transient and a persistent inward current that were both blocked by 0.1 μM TTX or by extracellular Na+ reduction. In conclusion, most A5 neurons are spontaneously active in vitro. They display irregular subthreshold membrane potential oscillations generated by voltage-activated conductances that include a persistent TTX-sensitive Na+ current. Most of the activity of A5 cells appears due to intrinsic properties rather than to synaptic inputs.

scholarly journals Alterations in the intrinsic properties of striatal cholinergic interneurons after dopamine lesion and chronic L-DOPA

2020 ◽  
Author(s):  
Se Joon Choi ◽  
Thong C. Ma ◽  
Yunmin Ding ◽  
Timothy Cheung ◽  
Neal Joshi ◽  
...  
Keyword(s):  
Normal Activity ◽  
Sk Channels ◽  
Intrinsic Properties ◽  
Therapeutic Approaches ◽  
Physiological Basis ◽  
Cholinergic Interneurons ◽  
Pharmacological Blockade ◽  
Cholinergic Interneuron ◽  
Spontaneous Firing Rate ◽  
Small Conductance

SummaryChanges in striatal cholinergic interneuron (ChI) activity are thought to contribute to Parkinson’s disease pathophysiology and dyskinesia from chronic L-3,4-dihydroxyphenylalanine (L-DOPA) treatment, but the physiological basis of these changes are unknown. We find that dopamine lesion decreases the spontaneous firing rate of ChIs, whereas chronic treatment with L-DOPA of lesioned mice increases baseline ChI firing rates to levels beyond normal activity. The effect of dopamine loss on ChIs was due to decreased currents of both hyperpolarization-activated cyclic nucleotide-gated (HCN) and small conductance calcium-activated potassium (SK) channels. L-DOPA reinstatement of dopamine normalized HCN activity, but SK current remained depressed. Pharmacological blockade of HCN and SK activities mimicked changes in firing, confirming that these channels are responsible for the molecular adaptation of ChIs to dopamine loss and chronic L-DOPA treatment. These findings suggest that targeting ChIs with channel-specific modulators may provide therapeutic approaches for alleviating L-DOPA-induced dyskinesia in PD patients.

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