Cesium: postjunctional repetitive firing in sympathetic ganglion

Bullfrog ganglion cells in Cs⁺-Ringer's solution developed postjunctional repetitive spike responses to single preganglionic stimuli but not to single antidromic or direct stimuli. This action of Cs⁺ is equivalent to that of the neostigmine-like drugs and is apparently generated by primary action on presynaptic nerve terminals. Alterations of K⁺ and Na⁺ currents in the nerve terminal membrane could be the underlying mechanism.     

A model for repetitive firing in neurons

This paper describes a model for the generation of repetitive firing patterns in single neurons to be used as a module in large-scale network simulation studies. The model is based on the combination of extended versions of Hill's model for accomodation and of Kernell's model for adaptation. Both digital computer and electronic circuit realizations of the model are presented. The model is shown to produce strength-duration curves for accomodation which are compatible with available data from real neurons. Both “high ceiling” and “low ceiling” cell types can be matched by adjusting parameters in the model. An equation relating steady-state firing rate to amplitude of applied steady current is presented which includes the accumulation of potassium conductance changes with repetitive firing. The occurence of phasic and tonic responses to step stimulation is mapped in the parameter space of the model. Several representative response patterns to irregular inputs are presented.     

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.     

Properties of repetitive firing in cat motor cortical neurons to membrane depolarizing currents

Acute experiments were carried out on immobilized cats under superficial pentobarbital (20 mg/kg) anesthesia to investigate the parameters of the rhythmic discharge of neurons in the motor cortex in the area of representation of the forelimb, evoked by passage of steps of depolarizing current through an intracellular microelectrode. The steady-state repetitive firing rate was found to be a linear function of the strength of the current passing through the membrane; no secondary range was discovered. The slope of the "discharge frequency — current" function (f/I=k) was 18±10.7 spikes/sec/nA. The regression line between the slope of the "discharge frequency-current" function and the input resistance (R_in) drawn by the method of least squares had the form k=0.68, R_in=–11.3. Two types of curve of adaptation of the discharge frequency to the stimulating current were found: exponential and undamped oscillations. The curve of latent period of the first action potential in the rhythmic discharge and the length of the first interspike interval as a function of current strength was shown to be a hyperbola, but with different scales along the abscissa. The connection between the properties of the dendritic tree and the parameters of the rhythmic discharge of cortical neurons is discussed.M. V. Lomonosov Moscow State University. Translated from Neirofiziologiya, Vol. 8, No. 5, pp. 476–482, September–October, 1976.     

Gain-of-function nature of Cav1.4 L-type calcium channels alters firing properties of mouse retinal ganglion cells

Proper function of Cav1.4 L-type calcium channels is crucial for neurotransmitter release in the retina. Our understanding about how different levels of Cav1.4 channel activity affect retinal function is still limited. In the gain-of-function mouse model Cav1.4-IT we expected a reduction in the photoreceptor dynamic range but still transmission toward retinal ganglion cells. A fraction of Cav1.4-IT ganglion cells responded to light stimulation in multielectrode array recordings from whole-mounted retinas, but showed a significantly delayed response onset. Another significant number of cells showed higher activity in darkness. In addition to structural remodeling observed at the first retinal synapse of Cav1.4-IT mice the functional data suggested a loss of contrast enhancement, a fundamental feature of our visual system. In fact, Cav1.4-IT mouse retinas showed a decline in spatial response and changes in their contrast sensitivity profile. Photoreceptor degeneration was obvious from the nodular structure of cone axons and enlarged pedicles which partly moved toward the outer nuclear layer. Loss of photoreceptors was also expressed as reduced expression of proteins involved in chemical and electrical transmission, as such metabotropic glutamate receptor mGluR6 and the gap junction protein Connexin 36. Such gross changes in retinal structure and function could also explain the diminished visual performance of CSNB2 patients. The expression pattern of the plasma-membrane calcium ATPase 1 which participates in the maintenance of the intracellular calcium homeostasis in photoreceptors was changed in Cav1.4-IT mice. This might be part of a protection mechanism against increased calcium influx, as this is suggested for Cav1.4-IT channels.     

Gain-of-function nature of Cav1.4 L-type calcium channels alters firing properties of mouse retinal ganglion cells

Proper function of Cav1.4 L-type calcium channels is crucial for neurotransmitter release in the retina. Our understanding about how different levels of Cav1.4 channel activity affect retinal function is still limited. In the gain-of-function mouse model Cav1.4-IT we expected a reduction in the photoreceptor dynamic range but still transmission toward retinal ganglion cells. A fraction of Cav1.4-IT ganglion cells responded to light stimulation in multielectrode array recordings from whole-mounted retinas, but showed a significantly delayed response onset. Another significant number of cells showed higher activity in darkness. In addition to structural remodeling observed at the first retinal synapse of Cav1.4-IT mice the functional data suggested a loss of contrast enhancement, a fundamental feature of our visual system. In fact, Cav1.4-IT mouse retinas showed a decline in spatial response and changes in their contrast sensitivity profile. Photoreceptor degeneration was obvious from the nodular structure of cone axons and enlarged pedicles which partly moved toward the outer nuclear layer. Loss of photoreceptors was also expressed as reduced expression of proteins involved in chemical and electrical transmission, as such metabotropic glutamate receptor mGluR6 and the gap junction protein Connexin 36. Such gross changes in retinal structure and function could also explain the diminished visual performance of CSNB2 patients. The expression pattern of the plasma-membrane calcium ATPase 1 which participates in the maintenance of the intracellular calcium homeostasis in photoreceptors was changed in Cav1.4-IT mice. This might be part of a protection mechanism against increased calcium influx, as this is suggested for Cav1.4-IT channels.     

Properties of mouse retinal ganglion cell dendritic growth during postnatal development

The property of dendritic growth dynamics during development is a subject of intense interest. Here, we investigated the dendritic motility of retinal ganglion cells (RGCs) during different developmental stages, using ex vivo mouse retina explant culture, Semliki Forest Virus transfection and time-lapse observations. The results illustrated that during development, the dendritic motility underwent a change from rapid growth to a relatively stable state, i.e., at P0 (day of birth), RGC dendrites were in a highly active state, whereas at postnatal 13 (P13) they were more stable, and at P3 and P8, the RGCs were in an intermediate state. At any given developmental stage, RGCs of different types displayed the same dendritic growth rate and extent. Since the mouse is the most popular mammalian model for genetic manipulation, this study provided a methodological foundation for further exploring the regulatory mechanisms of dendritic development.     

Changing dendritic field size of mouse retinal ganglion cells in early postnatal development

During early postnatal development, dendrites of retinal ganglion cells (RGCs) extend and branch in the inner plexiform layer to establish the adult level of stratification, pattern of branching, and coverage. Many studies have described the branching patterns, transient features, and regulatory factors of stratification of the RGCs. The rate of RGC dendritic field (DF) expansion relative to the growing retina has not been systematically investigated. In this study, we used two methods to examine the relative expansion of RGC DFs. First, we measured the size of RGC DFs and the diameters of the eyeballs at several postnatal stages. We compared the measurements with the RGC DF sizes calculated from difference of the eyeball sizes based on a linear expansion assumption. Second, we used the number of cholinergic amacrine cells (SACs) circumscribed by the DFs of RGCs at corresponding time points as an internal ruler to assess the size of DFs. We found most RGCs exhibit a phase of faster expansion relative to the retina between postnatal day 8 (P8) and P13, followed by a phase of retraction between P13 and adulthood. The morphological α cells showed the faster growing phase but not the retraction phase, whereas the morphological ON–OFF direction selective ganglion cells expanded in the same pace as the growing retina. These findings indicate different RGCs show different modes of growth, whereas most subtypes exhibit a fast expansion followed by a retraction phase to reach the adult size. © 2009 Wiley Periodicals, Inc. Develop Neurobiol 70: 397–407, 2010     

Spontaneous and repetitive driver potentials in crab cardiac ganglion neurons

Summary Driver potentials (DP), TTX-resistant voltage-activated slow depolarizations probably involving Ca⁺⁺-influx, have previously been shown to play an essential role in the organization of spike bursts in crustacean cardiac ganglia. The work reported here suggests that the DP system may also constitute an important component of the ganglionic oscillator.DPs were recorded intracellularly from neurons in ganglia isolated from two brachyurans,Portunus sanguinolentus and Podophthalmus vigil. InPortunus, full-sized DPs can be evoked in TTX by brief stimulus pulses only at invervals of several seconds; a single DP is triggered during a long (3-s) current pulse, and spontaneous DPs never occur. In contrast, nearly one half ofPodophthalmus preparations show spontaneous high-frequency trains of DPs lasting up to 5 min and recurring at irregular intervals. In allPodophthalmus preparations repetitive DPs are evoked during a 3-s pulse, and increase in frequency as current strength is increased. Portunus ganglia can be made to exhibit repetitive DPs in response to current if perfused with TEA (which suppresses a rectifying K⁺-current) in a medium with reduced Na⁺ (which is likely to enhance the inward Ca⁺⁺-current); neither TEA alone nor low-Na⁺ alone permits repetitive DPs. IfPortunus large cells are first conditioned at more negative voltages than normal, subsequent depolarizing current tends to induce large oscillations, and a second full DP may result in normal medium containing TTX.InPodophthalmus ganglia, single evoked DPs rise more rapidly and are shorter in duration than inPortunus; they are less effectively suppressed by Mn⁺⁺, but show similar Ca⁺⁺-dependency at lowered Ca⁺⁺ levels. Conditioning hyperpolarization slows the rate of rise of single evoked DPs and delays the onset of repetitive DPs during a 3-s pulse. A fast-K⁺ current appears to be more strongly activated inPodophthalmus.The results suggest (1) that oscillatory capability of the DP system may itself play an important role in the generation of rhythmic output by cardiac ganglia; and (2) differences in the V-dependence of Ca^{+ +}, delayed rectifying K⁺ and fast K⁺ currents may be responsible in diverse species for different tendency of the DP system to oscillate in TTX.Abbreviations DP driver potential - Rm membrane resistance - TEA tetraethylammonium - TTX tetrodotoxin - Vm membrane potential     

Modeling the variability of firing rate of retinal ganglion cells.

Impulse trains simulating the maintained discharges of retinal ganglion cells were generated by digital realizations of the integrate-and-fire model. If the mean rate were set by a "bias" level added to "noise," the variability of firing would be related to the mean firing rate as an inverse square root law; the maintained discharges of retinal ganglion cells deviate systematically from such a relationship. A more realistic relationship can be obtained if the integrate-and-fire mechanism is "leaky"; with this refinement, the integrate-and-fire model captures the essential features of the data. However, the model shows that the distribution of intervals is insensitive to that of the underlying variability. The leakage time constant, threshold, and distribution of the noise are confounded, rendering the model unspecifiable. Another aspect of variability is presented by the variance of responses to repeated discrete stimuli. The variance of response rate increases with the mean response amplitude; the nature of that relationship depends on the duration of the periods in which the response is sampled. These results have defied explanation. But if it is assumed that variability depends on mean rate in the way observed for maintained discharges, the variability of responses to abrupt changes in lighting can be predicted from the observed mean responses. The parameters that provide the best fits for the variability of responses also provide a reasonable fit to the variability of maintained discharges.     

Ionic mechanisms underlying tonic and phasic firing behaviors in retinal ganglion cells

In the retina, the firing behaviors that ganglion cells exhibit when exposed to light stimuli are very important due to the significant roles they play in encoding the visual information. However, the detailed mechanisms, especially the intrinsic properties that generate and modulate these firing behaviors is not completely clear yet. In this study, 2 typical firing behaviors—i.e., tonic and phasic activities, which are widely observed in retinal ganglion cells (RGCs)—are investigated. A modified computational model was developed to explore the possible ionic mechanisms that underlie the generation of these 2 firing patterns. Computational results indicate that the generation of tonic and phasic activities may be attributed to the collective actions of 2 kinds of adaptation currents, i.e., an inactivating sodium current and a delayed-rectifier potassium current. The concentration of magnesium ions has crucial but differential effects in the modulation of tonic and phasic firings, when the model neuron is driven by N-methyl-D-aspartate (NMDA) -type synaptic input instead of constant current injections. The proposed model has robust features that account for the ionic mechanisms underlying the tonic and phasic firing behaviors, and it may also be used as a good candidate for modeling some other firing patterns in RGCs.     

Response properties of mouse trigeminal ganglion neurons

We used controlled whisker deflections to examine the response properties of 208 primary afferent neurons in the trigeminal ganglion of adult mice. Proportions of rapidly adapting (RA, 47%) and slowly adapting (SA, 53%) neurons were equivalent, and most cells had low or no spontaneous activity. We quantified angular tuning and sensitivity to deflection amplitude and velocity. Both RA and SA units fired more frequently to larger deflections and faster deflections, but RA units were more sensitive to differences in velocity whereas SA units were more sensitive to deflection amplitudes. Almost all neurons were tuned for deflection angle, and the average response to the maximally effective direction was more than fourfold greater than the average response in the opposite direction; SA units were more tuned than RA units. Responses of primary afferent whisker-responsive neurons are qualitatively similar to those of the rat. However, average firing rates of both RA and SA neurons in the mouse are less sensitive to differences in deflection velocity, and RA units, unlike those in the rat, display amplitude sensitivity. Subtle observed differences between mice and rats may reflect greater mechanical compliance in mice of the whisker hairs and of the tissue in which they are embedded.     

Response properties of mouse trigeminal ganglion neurons

We used controlled whisker deflections to examine the response properties of 208 primary afferent neurons in the trigeminal ganglion of adult mice. Proportions of rapidly adapting (RA, 47%) and slowly adapting (SA, 53%) neurons were equivalent, and most cells had low or no spontaneous activity. We quantified angular tuning and sensitivity to deflection amplitude and velocity. Both RA and SA units fired more frequently to larger deflections and faster deflections, but RA units were more sensitive to differences in velocity whereas SA units were more sensitive to deflection amplitudes. Almost all neurons were tuned for deflection angle, and the average response to the maximally effective direction was more than fourfold greater than the average response in the opposite direction; SA units were more tuned than RA units. Responses of primary afferent whisker-responsive neurons are qualitatively similar to those of the rat. However, average firing rates of both RA and SA neurons in the mouse are less sensitive to differences in deflection velocity, and RA units, unlike those in the rat, display amplitude sensitivity. Subtle observed differences between mice and rats may reflect greater mechanical compliance in mice of the whisker hairs and of the tissue in which they are embedded.     

Ion channel density and threshold dynamics of repetitive firing in a cortical neuron model

Modifying the density and distribution of ion channels in a neuron (by natural up- and down-regulation, by pharmacological intervention or by spontaneous mutations) changes its activity pattern. In the present investigation, we analyze how the impulse patterns are regulated by the density of voltage-gated channels in a model neuron, based on voltage clamp measurements of hippocampal interneurons. At least three distinct oscillatory patterns, associated with three distinct regions in the Na-K channel density plane, were found. A stability analysis showed that the different regions are characterized by saddle-node, double-orbit, and Hopf bifurcation threshold dynamics, respectively. Single strongly graded action potentials occur in an area outside the oscillatory regions, but less graded action potentials occur together with repetitive firing over a considerable range of channel densities. The presently found relationship between channel densities and oscillatory behavior may be relevance for understanding principal spiking patterns of cortical neurons (regular firing and fast spiking). It may also be of relevance for understanding the action of pharmacological compounds on brain oscillatory activity.     

The early development of retinal ganglion cells with uncrossed axons in the mouse: retinal position and axonal course

The carbocyanine dye, DiI, has been used to study the retinal origin of the uncrossed retinofugal component of the mouse and to show the course taken by these fibres through the optic nerve and chiasm during development. Optic axons first arrive at the chiasm at embryonic day 13 (E13) but do not cross the midline until E14. After this stage, fibres taking an uncrossed course can be selectively labelled by unilateral tract implants of DiI. The earliest ipsilaterally projecting ganglion cells are located in the dorsal central retina. The first sign of the adult pattern of distribution of ganglion cells with uncrossed axons located mainly in the ventrotemporal retina is seen on embryonic day 16.5, thus showing that the adult line of decussation forms early in development. A small number of labelled cells continue to be found in nasal and dorsal retina at all later stages. At early stages (E14-15), retrogradely labelled uncrossed fibres are found in virtually all fascicles of the developing nerve, intermingling with crossed axons throughout the length of the nerve. At later stages of development (E16-17), although uncrossed fibres pass predominantly within the temporal part of the stalk, they remain intermingled with crossed axons. A significant number of uncrossed axons also lie within the nasal part of the optic stalk. The position of uncrossed fibres throughout the nerve in the later developmental stages is comparable to that seen in the adult rodent (Baker and Jeffery, 1989). The distribution of uncrossed axons thus indicates that positional cues are not sufficient to account for the choice made by axons when they reach the optic chiasm.     

Retinal ganglion cell differentiation in cultured mouse retinal explants

The availability of genetically engineered mice harboring specific mutations in genes affecting one or more retinal cell types affords new opportunities for investigating the genetic regulatory mechanisms of vertebrate retina formation. When identifying critical regulatory genes involved in retina development it is often advantageous to complement in vivo analysis with in vitro characterization. In particular, by combining classical techniques of retinal explant culturing with gene transfer procedures relying on herpes simple virus (HSV) amplicon vectors, gain-of-function analysis with genes of interest can be performed quickly and efficiently. Here, details are provided for isolating and culturing explants containing retinal progenitor cells and for infecting the explants with HSV expression vectors that perturb or rescue retinal ganglion cells, the first cell type to differentiate in the retina. In addition, the availability of sensitive techniques to monitor gene expression, including detection of reporter gene expression using antibodies and detection of endogenous marker gene expression using quantitative RT-PCR, provides an effective means for comparing wild-type and mutant retinas from genetically engineered mice.     

受损背根节神经元对四乙基胺反应的敏感性与其放电型式的关系

为了研究受损背根节神经元的放电型式与其对钾离子通道阻断剂四乙基胺（ｔｅｔｒａｅｔｈｙｌａｍｍｏｎｉｕｍ,ＴＥＡ）反应敏感性的关系,在大鼠背根节慢性压迫模型上记录单纤维自发放电。这些自发放电有周期和非周期两种型式,ＴＥＡ（２ｍｍｏｌ／Ｌ）分别引起２７．３％的周期放电神经元和９３．２％的非周期放电神经元 放电增加（Ｐ〈０．０１）。非周期放电神经元对不同浓度的ＴＥＡ的反应均比周期放电神经元大（Ｐ〈０．０