The Kv4.2 mediates excitatory activity-dependent regulation of neuronal excitability in rat cortical neurons

Neuronal excitability can cooperate with synaptic transmission to control the information storage. This regulation of neuronal plasticity can be affected by alterations in neuronal inputs and accomplished by modulation of voltage-dependent ion channels. In this study, we report that enhanced excitatory input negatively regulated neuronal excitability. Enhanced excitatory input by glutamate, electric field stimulation or high K⁺ increased transient outward K⁺ current, whereas did not affect the delayed rectifier K⁺ current in rat cultured cortical neurons. Both the voltage-dependent K⁺ channel 4.2 and 4.3 subunits contributed to the increase. The increase in the K⁺ current density by Kv4.2 was ascribed to its cytoplasmic membrane translocation, which was mediated by NMDA type of glutamate receptor. Furthermore, enhanced excitatory input inhibited neuronal excitability. Taken together, our results suggest that excitatory neurotransmission affects neuronal excitability via the regulation of the K⁺ channel membrane translocation.     

Mitochondrial dysfunction and increased sensitivity to excitotoxicity in mice deficient in DNA mismatch repair

The expression profile in the hippocampus of mice lacking one allele of the MutS homologue (Msh2), gene, which is one of the most representative components of the DNA mismatch repair system, was analysed to understand whether defects in the repair or in response to DNA damage could impact significantly on brain function. The overall results suggested a reduction in mitochondrial function as indicated by gene expression analysis, biochemical and behavioural studies. In the hippocampus of Msh2+/- mice, array data, validated by RT-PCR and western blot analysis, showed reduced expression levels of genes for cytochrome c oxidase subunit 2 (CoxII), ATP synthase subunit beta and superoxide dismutase 1. Biochemically, mitochondria from the hippocampus and cortex of these mice show reduced CoxII and increased aconitase activity. Behaviourally, these alterations resulted in mice with increased vulnerability to kainic acid-induced epileptic seizures and hippocampal neuronal loss. These data suggest that lack of an efficient system involved in recognizing and repairing DNA damage may generate a brain mitochondriopathy.     

Transition between two excitabilities in mesencephalic V neurons

Neurons can make different responses to identical inputs. According to the emerging frequency of repetitive firing, neurons are classified into two types: type 1 and type 2 excitability. Though in mathematical simulations, minor modifications of parameters describing ionic currents can result in transitions between these two excitabilities, empirical evidence to support these theoretical possibilities is scarce. Here we report a joint theoretical and experimental study to test the hypothesis that changes in parameters describing ionic currents cause predictable transitions between the two excitabilities in mesencephalic V (Mes V) neurons. We developed a simple mathematical model of Mes V neurons. Using bifurcation analysis and model simulation, we then predicted that changes in conductance of two low-threshold currents would result in transitions between type 1 and type 2. Finally, by applying specific channel blockers, we observed the transition between two excitabilities forecast by the mathematical model.     

The development of intrinsic excitability in mouse retinal ganglion cells

Activity-dependent refinement of synaptic connections occurs throughout the developing nervous system, including the visual system. Retinal ganglion cells (RGCs) overproduce synapses then refine them in an activity-dependent manner that segregates RGC connections into multicellular patterns, such as eye-specific regions and retinotopic maps. Ferrets additionally segregate ON and OFF retinogeniculate pathways in an activity-dependent manner. It was unknown whether differences in ON versus OFF intrinsic and spontaneous activity occur in postnatal mouse. The work reported here measured the intrinsic properties and spontaneous activity of morphologically identified postnatal mouse RGCs, and tested the hypothesis that mouse ON and OFF RGCs develop differences in spontaneous activity. We found developmental changes in resting potential, action potential threshold, depolarization to threshold, action potential width, action potential patterns, and maximal firing rates. These results are consistent with the maturation of the intrinsic properties of RGCs extending through the first three postnatal weeks. However, there were no differences among mouse ON, OFF, and multistratified RGCs in intrinsic excitability, spontaneous synaptic drive or spontaneous action potential patterns. The absence of differences between ON and OFF activity patterns is unlike the differences that arise in ferrets. In contrast to the ferret, the ON and OFF target neurons in the mouse are organized in a random pattern, not layers. This supports the hypothesis that the absence of systematic differences in activity results in the nonlayered distribution of retinogeniculate connections.     

Evoked Activity of Afferent and Efferent Fibers of the Sciatic Nerve in Rats under Conditions of Experimental Hyperthyroidism

In Wistar albino rats with experimental hyperthyroidism (HTh) and control animals, we measured parameters of the responses evoked in peripheral segments of the ventral and dorsal roots (VR and DR, respectively) by stimulation of the sciatic nerve. We found that the chronaxia of the afferent fibers of the sciatic nerve in HTh animals is shorter, while the duration of the mass action potential (AP) in the DR is somewhat longer than in the control. Under conditions of HTh, the excitation threshold of the efferent fibers became higher, the chronaxia decreased, and the second high-amplitude component could appear in the AP recorded from the VR. Possible mechanisms of changes in the excitability of afferent and efferent fibers of the sciatic nerve and specific features of the AP recorded from the VR under HTh conditions are discussed. In particular, we consider the possibility of ephaptic spreading of excitation in VR fibers under HTh conditions.     

Calcium signal‐dependent plasticity of neuronal excitability developed postnatally

Neuronal plasticity and its development were investigated at pyramidal neurons in the cortical slices of rats. The threshold and probability of firing spikes were measured by using whole‐cell recording to assess neuronal excitability. Postsynaptic high frequency activity (HFA) at the pyramidal neurons, evoked by 20 trains (250‐ms interval) of five depolarization‐pulses (1 ms) at 100 Hz, persistently lowered the threshold and increased the probability of firing spikes. After long‐term enhancement of neuronal excitability by HFA was stable, another HFA induced further enhancement. Infusing 1 mM 1,2‐bis(2‐aminophenoxy)‐ethane‐N, N,N′,N′‐tetraacetic acid or 100 μM CaMKII(281–301) into the recording neurons prevented HFA‐induced long‐term enhancement of neuronal excitability. The infusion of 40 μM calcineurin autoinhibitory peptide enhanced neuronal excitability, which occluded HFA effect. HFA‐induced long‐term enhancement of intrinsic excitability expressed at most pyramidal neurons after postnatal day (PND) 14, but not at those before PND 9. Our results show a new type of neuronal plasticity induced by physiological activity at cortical neurons, which requires calcium‐dependent protein phosphorylation and develops during postnatal period. An upregulation of intrinsic excitability at cortical neurons facilitates their activity and broadens signal codes; consequently, their computational ability is upgraded. © 2004 Wiley Periodicals, Inc. J Neurobiol, 2004     

铝对心肌细胞动作电位及其兴奋性的影响

目的 :观察氯化铝 (AlCl3)对豚鼠乳头状肌动作动位及其兴奋性的影响。方法 :利用细胞内微电极技术引导动作电位 (AP) ,经微机采集AP图形并测算跨膜电位各参数。结果 :①AlCl30 .5 ,1,2 ,4mmol/L使动作电位复极5 0 %时程 (APD50 )和复极 10 0 %时程 (APD10 0 )先延长后大幅度缩短 ,呈现双相效应 ,其中AlCl32mmol/L作用 5min时使APD50 从 (182± 2 7)ms延长至 (2 0 2± 3 2 )ms(P <0 0 5 ) ,作用 3 0min时使APD50 缩短至 (14 4± 17)ms(P <0 0 1) ;②AlCl32 ,4mmol/L使动作电位幅度 (APA)及 0期最大除极速度 (Vmax)减小 ,兴奋性下降。结论 :AlCl3可能对Na 内流有抑制作用 ,对Ca2 内流呈现先促进后抑制的双相效应。     

Neuromodulatory Selection of Motor Neuron Recruitment Patterns in a Visuomotor Behavior Increases Speed

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Effects of the venom of Philanthus triangulum F. (Hym. sphecidae) and β- and δ-philanthotoxin on axonal excitability and synaptic transmission in the cockroach CNS

This paper provides answers to the questions which of the toxins present in the venom of the wasp Philanthus triangulum may be responsible for the previously reported blockage of transmission through the sixth abdominal ganglion of the cockroach, and whether this may occur by block of synaptic transmission or by affecting axonal exitability. In current clamp experiments the crude venom induces a slight depolarization of the membrane of the giant axon from the sixth abdominal ganglion of the cockroach and a small and irreversible decrease in the amplitude of the action potential. These marginal effects are not seen with relatively high concentrations of the philanthotoxins β-PTX and δ-PTX. It appears that neither the crude venom nor the toxins significantly affect the excitability of the cockroach giant axon. At a concentration of 20 μg ml^?1 δ-PTX causes a slowly reversible block of synaptic transmission from the cercal nerve XI to a giant interneuron without any change in resting membrane potential, whereas β-PTX is inactive. Iontophoretically evoked acetylcholine potentials of the giant neuron are more sensitive to δ-PTX than excitatory postsynaptic potentials. This suggests that the toxin acts on the postsynaptic membrane.