Membrane Potential Oscillations Research Articles

A Model of Intracellular Theta Phase Precession Dependent on Intrinsic Subthreshold Membrane Currents

A hippocampal place cell fires at an increasingly earlier phase in relation to the extracellular theta rhythm as a rodent moves through the place field. The present report presents a compartment model of a CA1 pyramidal cell that explains the increase in amplitude and the phase precession of intracellular theta oscillations, with the assumption that the cell receives an asymmetric ramp depolarization (<10 mV) in the place field and rhythmic inhibitory and/or excitatory synaptic driving. Intracellular subthreshold membrane potential oscillations (MPOs) increase in amplitude and frequency, and show phase precession within the place field. Theta phase precession and MPO power and frequency increase in the place field are caused by a shift in excitatory-inhibitory response, intrinsic theta-frequency resonance, and intrinsic oscillations that depend on voltage-dependent persistent Na(+) and slowly inactivating K(+) currents, but not on I(h). Phase precession is diminished when theta-frequency resonance is decreased. Simulated spikes fire near the peak of MPOs and precess similarly as the MPOs. The phase of the MPOs/spikes codes for distance in a one-dimensional place field, and phase precession is only weakly dependent on firing rate, running speed, or the duration needed to cross the place field. In addition, phase precession within the place field resumes quickly after disruption by maximal afferent pulse stimulation.

Initiation of segmental locomotor-like activities by stimulation of ventrolateral funiculus in the neonatal rat

Descending control is critically important for the generation of locomotor activities. Yet, our understanding of the descending control system of locomotion is limited. We hypothesized that stimulation of the ventrolateral funiculus (VLF) induces rhythmic activity in lumbar neurons that is correlated with locomotor-like activity in the neonatal rat. Intracellular recordings were conducted in the L2-L3 lumbar segments, while locomotor-like output was monitored in the L2 and L5 ventral roots. Stimulation of the VLF at thoracic segments induced locomotor-like activity in the L2 and L5 ventral roots in majority of the preparations (26/33). In a few midline split cord preparations (4/13), VLF stimulation induced rhythmic locomotor-like bursts in either L2 or L5 ventral root without alternating pattern between the ventral roots. The response latencies suggest that VLF stimulation induced antidromic activation (<1ms, 8 cells), monosynaptic activation (1-3ms, 18 cells), and oligosynaptic activation (3.5-5ms, 14 cells) of segmental neurons in the lumbar region. VLF stimulation induced rhythmic membrane potential oscillations with or without bursting of action potentials in 9 of 40 putative interneurons. The membrane potential oscillations were in phase with the locomotor-like output of the L2 ventral root in 7 of the 9 cells while the other 2 cells oscillated in phase with the L5 ventral root activity. We have thus demonstrated that descending axons exist in the VLF which make synaptic connections with segmental neurons in the lumbar region that may be a critical element of the locomotor neural network for the initiation of locomotion.

In vivo conditions induce faithful encoding of stimuli by reducing nonlinear synchronization in vestibular sensory neurons.

Previous studies have shown that neurons within the vestibular nuclei (VN) can faithfully encode the time course of sensory input through changes in firing rate in vivo. However, studies performed in vitro have shown that these same VN neurons often display nonlinear synchronization (i.e. phase locking) in their spiking activity to the local maxima of sensory input, thereby severely limiting their capacity for faithful encoding of said input through changes in firing rate. We investigated this apparent discrepancy by studying the effects of in vivo conditions on VN neuron activity in vitro using a simple, physiologically based, model of cellular dynamics. We found that membrane potential oscillations were evoked both in response to step and zap current injection for a wide range of channel conductance values. These oscillations gave rise to a resonance in the spiking activity that causes synchronization to sinusoidal current injection at frequencies below 25 Hz. We hypothesized that the apparent discrepancy between VN response dynamics measured in in vitro conditions (i.e., consistent with our modeling results) and the dynamics measured in vivo conditions could be explained by an increase in trial-to-trial variability under in vivo vs. in vitro conditions. Accordingly, we mimicked more physiologically realistic conditions in our model by introducing a noise current to match the levels of resting discharge variability seen in vivo as quantified by the coefficient of variation (CV). While low noise intensities corresponding to CV values in the range 0.04–0.24 only eliminated synchronization for low (<8 Hz) frequency stimulation but not high (>12 Hz) frequency stimulation, higher noise intensities corresponding to CV values in the range 0.5–0.7 almost completely eliminated synchronization for all frequencies. Our results thus predict that, under natural (i.e. in vivo) conditions, the vestibular system uses increased variability to promote fidelity of encoding by single neurons. This prediction can be tested experimentally in vitro.

Firing frequency response to current and conductance periodic inputs in a Ih/INap biophysical neuron model

Various neurons exhibit membrane potential (or subthreshold) resonance [1], a peak in the subthreshold voltage amplitude response to oscillatory current inputs at a certain preferred (resonant) input frequency. Previous theoretical work using linear models has shown that subthreshold resonance can be communicated to the supra-threshold regime [2,3]; i.e., the firing frequency (or signal gain) response to oscillatory input currents peaks at the subthreshold resonant frequency. Whether this property is maintained under more general conditions and for different types of inputs is still an open question. In this work, we investigate the firing frequency patterns generated in response to both current and conductance sinusoidal inputs in a biophysical (conductance-based) neuron model that includes two ionic currents: h- (Ih) and persistent sodium (INap). This model is based on measurements for stellate cells (SCs) in layer II of the medial entorhinal cortex [4] and captures various phenomena observed in SCs such as membrane potential oscillations and membrane potential (subthreshold) resonance at theta frequencies (4 - 10 Hz)[2]. The Ih/INap model describes the cell's subthreshold dynamics and the onset of spikes [5]. Spikes were generated artificially as in integrate/resonate-and-fire models (see [5]). We computed the firing rate and signal gain responses of the Ih/INap model to both current and conductance sinusoidal inputs for a wide range of frequencies and input amplitudes (Ain). The resulting patterns for current and conductance input are qualitatively different. For current inputs, the firing frequency (and signal gain) patterns show up to three prominent peaks with heights that differ only slightly. The number of peaks increases with increasing values of Ain. For small values of Ain, the peak input frequency coincides with the subthreshold resonant frequency. The voltage traces (voltage vs. time) corresponding different peaks for the same value of Ain have roughly the same number of spikes (and inter-spike intervals of similar size), and differ in the number of subthreshold oscillations interspersed in between two consecutive spikes. For conductance (excitatory) inputs, the firing rate patterns show multiple peaks with different heights. As Ain increases, the highest peak moves to the right. For input frequencies above 60 Hz, the firing rate and gain of the highest peak significantly increases relative to other peaks for the same value of Ain. This prominent peak reflects the fast time scale present in the model that has been shown to underlie hyper-excitable firing in SCs [6] observed in animal models of temporal lobe epilepsy. We use dynamical systems tools to explain the mechanism that govern the generation of the firing frequency patterns described above. We show that the nonlinearities present in the model and the time scale separation between voltage and the h-current gating variables play an important role in determining these patterns.

Neural Dynamics during Anoxia and the “Wave of Death”

Recent experiments in rats have shown the occurrence of a high amplitude slow brain wave in the EEG approximately 1 minute after decapitation, with a duration of 5–15 s (van Rijn et al, PLoS One 6, e16514, 2011) that was presumed to signify the death of brain neurons. We present a computational model of a single neuron and its intra- and extracellular ion concentrations, which shows the physiological mechanism for this observation. The wave is caused by membrane potential oscillations, that occur after the cessation of activity of the sodium-potassium pumps has lead to an excess of extracellular potassium. These oscillations can be described by the Hodgkin-Huxley equations for the sodium and potassium channels, and result in a sudden change in mean membrane voltage. In combination with a high-pass filter, this sudden depolarization leads to a wave in the EEG. We discuss that this process is not necessarily irreversible.

Periodic stimulation induces long-range modulation of cortical responses and visual perception

Periodic sensory stimuli are prevalent in natural environment and may signal events of particular importance. However, whether periodic and aperiodic stimuli are differentially processed by neural circuits remains unclear. Here we show that periodic stimuli exert influences over longer distances than aperiodic stimuli at both neuronal and perceptual levels. Whole-cell recording from rat visual cortex showed that periodic visual stimulation (1-11 Hz) outside the neuronal receptive field evoked robust membrane potential oscillation at the stimulation frequency, while the same stimulus applied aperiodically had little effect. Human psychophysical experiments showed that periodic luminance changes in the distant surround also exert a stronger modulation of perceived brightness of a centre test stimulus than that exerted by aperiodic changes. Furthermore, both perceptual and neuronal modulation increased with the number of stimulation cycles for periodic surround stimuli. Thus, periodic stimuli can modulate both cortical responses and visual perception over larger spatial scales, generating more global impact on cortical information processing.

Dorsal–ventral organization of theta‐like activity intrinsic to entorhinal stellate neurons is mediated by differences in stochastic current fluctuations

The membrane potential dynamics of stellate neurons in layer II of the medial entorhinal cortex are important for neural encoding of location. Previous studies suggest that these neurons generate intrinsic theta-frequency membrane potential oscillations, with a period that depends on neuronal location on the dorsal–ventral axis of themedial entorhinal cortex, and which in behaving animals could support generation of grid-like spatial firing fields. To address the nature and organization of this theta-like activity, we adopt the Lombmethod of least-squares spectral analysis. We demonstrate that peaks in frequency spectra that differ significantly from Gaussian noise do not necessarily imply the existence of a periodic oscillator, but can instead arise from filtered stochastic noise or a stochastic random walk. We show that theta-like membrane potential activity recorded fromstellate neurons in mature brain slices is consistentwith stochastic mechanisms, but not with generation by a periodic oscillator. The dorsal–ventral organization of intrinsic theta-likemembrane potential activity, and themodification of this activity during block of HCN channels, both reflect altered frequency distributions of stochastic spectral peaks, rather than tuning of a periodic oscillator. Our results demonstrate the importance of distinguishing periodic oscillations from stochastic processes.We suggest that dorsal–ventral tuning of theta-like membrane potential activity is due to differences in stochastic current fluctuations resulting from organization of ion channels that also control synaptic integration.

Dynamic modulation of Ca 2+ sparks by mitochondrial oscillations in isolated guinea pig cardiomyocytes under oxidative stress

Local control of Ca 2+-induced Ca 2+ release (CICR) depends on the spatial organization of L-type Ca 2+ channels and ryanodine receptors (RyR) in the dyad. Analogously, Ca 2+ uptake by mitochondria is facilitated by their close proximity to the Ca 2+ release sites, a process required for stimulating oxidative phosphorylation during changes in work. Mitochondrial feedback on CICR is less well understood. Since mitochondria are a primary source of reactive oxygen species (ROS), they could potentially influence the cytosolic redox state, in turn altering RyR open probability. We have shown that self-sustained oscillations in mitochondrial inner membrane potential (ΔΨ m), NADH, ROS, and reduced glutathione (GSH) can be triggered by a laser flash in cardiomyocytes. Here, we employ this method to directly examine how acute changes in energy state dynamically influence resting Ca 2+ spark occurrence and properties. Two-photon laser scanning microscopy was used to monitor cytosolic Ca 2+ (or ROS), ΔΨ m, and NADH (or GSH) simultaneously in isolated guinea pig cardiomyocytes. Resting Ca 2+ spark frequency increased with each ΔΨ m depolarization and decreased with ΔΨ m repolarization without affecting Ca 2+ spark amplitude or time-to-peak. Stabilization of mitochondrial energetics by pretreatment with the superoxide scavenger TMPyP, or by acute addition of 4′-chlorodiazepam, a mitochondrial benzodiazepine receptor antagonist that blocks the inner membrane anion channel, prevented or reversed, respectively, the increased spark frequency. Cyclosporine A did not block the ΔΨ m oscillations or prevent Ca 2+ spark modulation by ΔΨ m. The results support the hypothesis that mitochondria exert an influential role on the redox environment of the Ca 2+ handling subsystem, with mechanistic implications for the pathophysiology of cardiac disease.

Generation of Locomotion Rhythms Without Inhibition in Vertebrates: The Search for Pacemaker Neurons

Locomotion rhythms are thought to be generated by neurons in the central-pattern-generator (CPG) circuit in the spinal cord. Synaptic connections in the CPG and pacemaker properties in certain CPG neurons, both may contribute to generation of the rhythms. In the half-center model proposed by Graham Brown a century ago, reciprocal inhibition plays a critical role. However, in all vertebrate preparations examined, rhythmic motor bursts can be induced when inhibition is blocked in the spinal cord. Without inhibition, neuronal pacemaker properties may become more important in generation of the rhythms. Pacemaker properties have been found in motoneurons and some premotor interneurons in different vertebrates and they can be dependent on N-Methyl-d-aspartate (NMDA) receptors (NMDAR) or rely on other ionic currents like persistent inward currents. In the swimming circuit of the hatchling Xenopus tadpole, there is substantial evidence that emergent network properties can give rise to swimming rhythms. During fictive swimming, excitatory interneurons (dINs) in the caudal hindbrain fire earliest on each swimming cycle and their spikes drive the firing of other CPG neurons. Regenerative dIN firing itself relies on reciprocal inhibition and background excitation. We now find that the activation of NMDARs can change dINs from firing singly at rest to current injection to firing repetitively at swimming frequencies. When action potentials are blocked, some intrinsic membrane potential oscillations at about 10 Hz are revealed, which may underlie repetitive dIN firing during NMDAR activation. In confirmation of this, dIN repetitive firing persists in NMDA when synaptic transmission is blocked by Cd(2+). When inhibition is blocked, only dINs and motoneurons are functional in the spinal circuit. We propose that the conditional intrinsic NMDAR-dependent pacemaker firing of dINs can drive the production of swimming-like rhythms without the participation of inhibitory neurotransmission.

Blockade of Persistent Sodium Currents Contributes to the Riluzole-Induced Inhibition of Spontaneous Activity and Oscillations in Injured DRG Neurons

In addition to a fast activating and immediately inactivating inward sodium current, many types of excitable cells possess a noninactivating or slowly inactivating component: the persistent sodium current (INaP). The INaP is found in normal primary sensory neurons where it is mediated by tetrodotoxin-sensitive sodium channels. The dorsal root ganglion (DRG) is the gateway for ectopic impulses that originate in pathological pain signals from the periphery. However, the role of INaP in DRG neurons remains unclear, particularly in neuropathic pain states. Using in vivo recordings from single medium- and large-diameter fibers isolated from the compressed DRG in Sprague-Dawley rats, we show that local application of riluzole, which blocks the INaP, also inhibits the spontaneous activity of A-type DRG neurons in a dose-dependent manner. Significantly, riluzole also abolished subthreshold membrane potential oscillations (SMPOs), although DRG neurons still responded to intracellular current injection with a single full-sized spike. In addition, the INaP was enhanced in medium- and large-sized neurons of the compressed DRG, while bath-applied riluzole significantly inhibited the INaP without affecting the transient sodium current (INaT). Taken together, these results demonstrate for the first time that the INaP blocker riluzole selectively inhibits INaP and thereby blocks SMPOs and the ectopic spontaneous activity of injured A-type DRG neurons. This suggests that the INaP of DRG neurons is a potential target for treating neuropathic pain at the peripheral level.

Inputs Underlying the ON–OFF Light Responses of Type 2 Wide-Field Amacrine Cells in TH::GFP Mice

In the mammalian retina, two types of catecholaminergic amacrine cells have been described. Although dopaminergic type 1 cells are well characterized, the physiology of type 2 cells is, so far, unknown. To target type 2 cells specifically, we used a transgenic mouse line that expresses green fluorescent protein under the control of the tyrosine hydroxylase promoter. Type 2 cells are GABAergic and have an extensive dendritic arbor, which stratifies in the middle of the inner plexiform layer. Our data suggest that type 2 cells comprise two subpopulations with identical physiological properties: one has its somata located in the inner nuclear layer and the other in the ganglion cell layer. Immunostaining with bipolar cell markers suggested that type 2 cells receive excitatory inputs from type 3 OFF and type 5 ON bipolar cells. Consistently, patch-clamp recordings showed that type 2 cells are ON-OFF amacrine cells. Blocking excitatory inputs revealed that different rod and cone pathways are active under scotopic and mesopic light conditions. Blockade of inhibitory inputs led to membrane potential oscillations in type 2 cells, suggesting that GABAergic and glycinergic amacrine cells strongly influence type 2 cell signaling. Among the glycinergic amacrine cells, we identified the VGluT3-immunoreactive amacrine cell as a likely candidate. Collectively, light responses of type 2 cells were remarkably uniform over a wide range of light intensities. These properties point toward a general function of type 2 cells that is maintained under scotopic and mesopic conditions.

Modelling intrinsic electrophysiological properties of ON and OFF retinal ganglion cells

ON and OFF retinal ganglion cells (RGCs) display differences in their intrinsic electrophysiology: OFF cells maintain spontaneous activity in the absence of any input, exhibit subthreshold membrane potential oscillations, rebound excitation and burst firing; ON cells require excitatory input to drive their activity and display none of the aforementioned phenomena. The goal of this study was to identify and characterize ionic currents that explain these intrinsic electrophysiological differences between ON and OFF RGCs. A mathematical model of the electrophysiological properties of ON and OFF RGCs was constructed and validated using published patch-clamp data from isolated intact mouse retina. The model incorporates three ionic currents hypothesized to play a role in generating behaviors that are different between ON and OFF RGCs. These currents are persistent Na( + ), I (NaP), hyperpolarization-activated, I (h), and low voltage activated Ca(2 + ), I (T), currents. Using computer simulations of Hodgkin-Huxley type neuron with a single compartment model we found two distinct sets of I (NaP), I (h), I (T) conductances that correspond to ON and OFF RGCs populations. Simulations indicated that special properties of I (T) explain the differences in intrinsic electrophysiology between ON and OFF RGCs examined here. The modelling shows that the maximum conductance of I (T) is higher in OFF than in ON cells, in agreement with recent experimental data.

Intracellular Calcium and Membrane Potential Oscillations in the Guinea Pig and Rat Pulmonary Vein Myocardium

Myocardial intracellular Ca2+ and membrane potential oscillations were studied in the isolated guinea-pig and rat pulmonary veins with immunohistochemical, confocal microscopic and electrophysiological analyses. The myocardial layer was present between the smooth muscle layer and the adventitia, and was more developed in the guinea-pig than in the rat. Intracellular Ca2+ oscillations were observed in both species, which were inhibited by ryanodine. Spontaneous Ca2+ waves were observed to propagate along the longitudinal axis of the cell or as a spiral rotating around a subcellular core; the propagation velocity of these Ca2+ waves was similar to that reported in atrial and ventricular cardiomyocytes. Spontaneous action potentials were present in about 35% and 4% of the preparations from the guinea-pig and rat, respectively. In quiescent preparations from the guinea-pig, noradrenaline induced a slow depolarization of the resting membrane potential followed by constant repetitive generation of action potentials, which were inhibited by ryanodine. In quiescent preparations from the rat, noradrenaline induced an initial hyperpolarization and a subsequent depolarization of the resting membrane potential. This was followed by generation of automatic action potentials which occurred in repetitive bursts. Ryanodine either abolished or reduced the duration of action-potential bursts. These results indicate that the pulmonary vein myocardium generates automatic electrical activity under adrenergic influence, which is probably triggered by intracellular Ca2+ oscillations. The difference in firing pattern between the guineapig and rat may be due to the difference in hyperpolarizing mechanisms. Abstract Conclusion

Інгібітор мітохондріального Na+-Ca2+-обмінника CGP37157 деполяризує ендотеліальні клітини та викликає осциляції мембранного потенціалу

We explored the effect of inhibitor of mitochondrial Na(+)-Ca(2+)-exchanger CGP37157 and the effect of mitochondria permeability transition pore inhibitor, cyclosporine A, on the membrane potential and electrical responses to endothelium-dependent dilators in intact endothelial cells from excised rat aorta and EA.hy 926 endothelial cells. Cyclosporin A did not affect the resting membrane potential and hyperpolarization to acetylcholine and histamine in intact and cultured cells. In contrast, CGP37157 (20 mcM) evoked membrane depolarization in unstimulated cells and suppressed the sustained component of hyperpolarization to acetylcholine and histamine both in intact and cultured endothelial cells, respectively. This was accompanied by a pronounced depolarization with membrane potential oscillations, which were not observed in the absence of Ca2+. We conclude that CGP37157 modulates endothelial membrane potential at rest and electrical responses to endothelium-dependent dilators. Possible mechanisms accompanying the CGP37157 action are discussed.

Dendritic versus somatic resonance

Event Abstract Back to Event Dendritic versus somatic resonance Ekaterina Zhuchkova1, 2* and Susanne Schreiber1, 2 1 Humboldt University, Institute for Theoretical Biology, Germany 2 Bernstein Center for Computational Neuroscience, Germany Membrane-potential resonance characterizes the ability of a neuron to selectively respond to stimuli in a preferred frequency band. It has been associated with the occurrence of subthreshold membrane-potential oscillations (MPOs) and has been shown to be of functional relevance, as exemplified by the correlation of resonance frequencies with the spacing of grid fields in the entorhinal cortex [1] and the dependence of this spacing on the resonating H current [2]. Resonance arises from the interaction of passive and active membrane properties, usually requiring the presence of slowly-activating conductances that act as high-pass filters and are able to effectively oppose slow changes of the membrane potential. The distribution of slow conductances responsible for resonance (like H or M), however, can differ between the compartments within a neuron. In CA1 neurons, for example, it is known that the density of H channels increases by more than 60-fold from soma to dendrites and is largest in the distal parts of the dendritic tree [3]. Accordingly, resonance can also depend on the spatial localization within a cell. Still, cells are usually classified as either resonant or nonresonant on the basis of somatic injection of ZAP currents (sine-wave functions with a linear increase in frequency). Here, we investigate to what extent and under which circumstances cells with dendritic resonance may be misclassified as nonresonant by somatic measurement of resonance properties. We use simple conductance-based multicompartmental models to analyze the effect of dendritic resonance on somatic input (and hence resonance estimates based on somatic recordings). We find that indeed, even a strong dendritic resonance may not be detectable with somatic ZAP protocols. The extent to which dendritic resonance is masked depends on neuronal morphology as well as the distribution of active conductances within the cell. In addition, we show that although dendritic resonance may not show up somatically, indirect consequences of dendritic resonance can affect the soma. In particular, MPOs of dendritic resonance-induced origin may propagate to the soma, leading to a situation where such cells when measured somatically do exhibit subthreshold MPOs in the apparent "absence" of resonance. A local dendritic resonance filters dendritic inputs - even if it should not show up somatically - and is hence crucial for the flow of information in neuronal networks. It is therefore important to identify the circumstances under which dendritic resonance could be missed in somatic assessment of resonance properties. Acknowledgements This work was supported by the DFG (SFB 618) and the BMBF (BCCN Berlin, BPCN).

Routing of information flow by selective visual attention in LFPs of monkey area V4

Routing of information flow by selective visual attention in LFPs of monkey area V4

Intracellular dynamics of virtual place cells.

The pattern of spikes recorded from place cells in the rodent hippocampus is strongly modulated by both the spatial location in the environment and the theta rhythm. The phases of the spikes in the theta cycle advance during movement through the place field. Recently intracellular recordings from hippocampal neurons (Harvey, Collman, Dombeck, & Tank, 2009 ) showed an increase in the amplitude of membrane potential oscillations inside the place field, which was interpreted as evidence that an intracellular mechanism caused phase precession. Here we show that an existing network model of the hippocampus (Tsodyks, Skaggs, Sejnowski, & McNaughton, 1996 ) can equally reproduce this and other aspects of the intracellular recordings, which suggests that new experiments are needed to distinguish the contributions of intracellular and network mechanisms to phase precession.

Specific Brainstem Neurons Switch Each Other into Pacemaker Mode to Drive Movement by Activating NMDA Receptors

Rhythmic activity is central to brain function. In the vertebrate CNS, the neuronal circuits for breathing and locomotion involve inhibition and also neurons acting as pacemakers, but identifying the neurons responsible has proven difficult. By studying simple hatchling Xenopus laevis tadpoles, we have already identified a population of electrically coupled hindbrain neurons (dINs) that drive swimming. During rhythm generation, dINs release glutamate to excite each other and activate NMDA receptors (NMDARs). The resulting depolarization enables a network mechanism for swimming rhythm generation that depends on reciprocal inhibition between antagonistic right and left sides. Surprisingly, a surgically isolated hemi-CNS without inhibition can still generate swimming-like rhythms. We have now discovered that activation of NMDARs transforms dINs, which normally fire singly to current injection, into pacemakers firing within the normal swimming frequency range (10-25 Hz). When dIN firing is blocked pharmacologically, this NMDAR activation produces 10 Hz membrane potential oscillations that persist when electrical coupling is blocked but not when the voltage-dependent gating of NMDARs by Mg²+ is removed. The NMDA-induced oscillations and pacemaker firing at swimming frequency are unique to the dIN population and do not occur in other spinal neurons. We conclude that NMDAR-mediated self-resetting switches critical neurons that drive swimming into pacemaker mode only during locomotion where it provides an additional, parallel mechanism for rhythm generation. This allows rhythm generation in a half-CNS and raises the possibility that such concealed pacemaker properties may be present underlying rhythm generation in other vertebrate brain networks.

Cellular Origin of Spontaneous Ganglion Cell Spike Activity in Animal Models of Retinitis Pigmentosa

Here we review evidence that loss of photoreceptors due to degenerative retinal disease causes an increase in the rate of spontaneous ganglion spike discharge. Information about persistent spike activity is important since it is expected to add noise to the communication between the eye and the brain and thus impact the design and effective use of retinal prosthetics for restoring visual function in patients blinded by disease. Patch-clamp recordings from identified types of ON and OFF retinal ganglion cells in the adult (36–210 d old) rd1 mouse show that the ongoing oscillatory spike activity in both cell types is driven by strong rhythmic synaptic input from presynaptic neurons that is blocked by CNQX. The recurrent synaptic activity may arise in a negative feedback loop between a bipolar cell and an amacrine cell that exhibits resonant behavior and oscillations in membrane potential when the normal balance between excitation and inhibition is disrupted by the absence of photoreceptor input.

Wavelet analysis reveals heterogeneous time-dependent oscillations of individual mitochondria

Mitochondrial inner membrane potential oscillations in cardiac myocytes synchronize under oxidative or metabolic stress, leading to synchronized whole cell oscillations. Gaining information about the temporal properties of individual mitochondrial oscillators is essential to comprehend the network's intrinsic spatiotemporal organization. We have developed methods to detect individual mitochondrial tetramethylrhodamine ethyl ester fluorescence oscillations and assess their dynamical properties using wavelet analysis. We demonstrate that these advanced signal processing tools can provide quantitative spatiotemporal information about intermitochondrial coupling. We have found that the mean frequency of selected groups of continuously oscillating mitochondria was 16.49 ± 1.04 mHz, whereas the mean frequency in the normalized mean global wavelet spectrum was 22.84 ± 1.80 mHz (n = 9 myocytes). In conclusion, this novel methodology will help shed new light on the dynamical properties of the mitochondrial network on the verge of synchronization.