Reduced spike-timing reliability correlates with the emergence of fast ripples in the rat epileptic hippocampus

Ripples are sharp-wave-associated field oscillations (100-300 Hz) recorded in the hippocampus during behavioral immobility and slow-wave sleep. In epileptic rats and humans, a different and faster oscillation (200-600 Hz), termed fast ripples, has been described. However, the basic mechanisms are unknown. Here, we propose that fast ripples emerge from a disorganized ripple pattern caused by unreliable firing in the epileptic hippocampus. Enhanced synaptic activity is responsible for the irregular bursting of CA3 pyramidal cells due to large membrane potential fluctuations. Lower field interactions and a reduced spike-timing reliability concur with decreased spatial synchronization and the emergence of fast ripples. Reducing synaptically driven membrane potential fluctuations improves both spike-timing reliability and spatial synchronization and restores ripples in the epileptic hippocampus. Conversely, a lower spike-timing reliability, with reduced potassium currents, is associated with ripple shuffling in normal hippocampus. Therefore, fast ripples may reflect a pathological desynchronization of the normal ripple pattern.     

Hippocampal ripple oscillations (200 Hz) in mechanisms of memory consolidation

A current status of knowledge about high-frequency (140-200 Hz) ripple oscillations in the CA1 hippocampal subfield is summarized and considered in the context of two-stage model of the hippocampal memory processing. A large body of evidence suggests highly-selective recruitment of pyramidal cells and interneurons in the generation of the oscillatory pattern after co-operative sharp-wave-related discharge of CA3 pyramidal neurons. We also discuss a role of transmission via gap junctions in the mechanisms of ripple oscillations as well as their adaptive aminergic (histaminergic) modulation. Patterns of neuronal firing in the hippocampus observed during ripple oscillations reproduce space-dependant neuronal activity from the previous waking period. Together with a data about efficacy of high-frequency stimulation for induction of synaptic modification it points out a role for ripples in the formation of long-term memory. Focal ultra fast ripples (up to 500 Hz) have been shown to participate in the development of temporal lobe epilepsy.     

Use of substratum ripples for flow refuging by Atlantic cod, Gadus morhua

The ability to maintain position in a current without actively swimming (station-holding) was measured on substratum ripples for Atlantic cod, Gadus morhua, a bentho-pelagic fusiform species. The current velocities tested ranged from 0–111 cm sec^-1. Ripples were sinusoidal, with twelve combinations of ripple wavelength (10, 25, 50, 125 cm) and ripple amplitude (1.0, 2.5, 5.0 cm). Ripple wavelengths were chosen to approximate 0.5, 1.0, 2.0 and 5.0 times fish total length. The potential of ripples to locally retard current and thereby provide a refuge from the flow was measured as a velocity ratio, u_trough/u_free-stream, where u_trough is the flow velocity measured at a height of 0.5 cm from the bottom of a trough and u_free-stream the flow velocity measured at a height of 10 cm above ripple crests. Cod usually swam steadily above substratum ripple crests in the free-stream flow. They used substratum ripples to hold station on only 3 of the 12 ripples tested by refuging from the flow in the ripple troughs (flow refuging). These ripples had wavelengths approaching twice the body length, with ripple amplitudes that produced velocity ratios of 0.44–0.65, thus providing at least a 35% flow reduction in the troughs. In addition, these ripples were only used at intermediate velocities starting at 49–78 cm sec^-1 and ending at 81–109 cm sec^-1 depending on the ripple morphology, suggesting there may be costs involved in flow refuging, probably in stability control. Flow refuging on substratum ripples could dramatically impact the physiology and ecology of cod in high current velocities by providing areas of retreat for energetic savings, but also offering opportunities for enhanced feeding and migration.     

Temperature-controlled structure and kinetics of ripple phases in one- and two-component supported lipid bilayers

Temperature-controlled atomic force microscopy (AFM) has been used to visualize and study the structure and kinetics of ripple phases in one-component dipalmitoylphosphatidylcholine (DPPC) and two-component dimyristoylphosphatidylcholine-distearoylphosphatidylcholine (DMPC-DSPC) lipid bilayers. The lipid bilayers are mica-supported double bilayers in which ripple-phase formation occurs in the top bilayer. In one-component DPPC lipid bilayers, the stable and metastable ripple phases were observed. In addition, a third ripple structure with approximately twice the wavelength of the metastable ripples was seen. From height profiles of the AFM images, estimates of the amplitudes of the different ripple phases are reported. To elucidate the processes of ripple formation and disappearance, a ripple-phase DPPC lipid bilayer was taken through the pretransition in the cooling and the heating direction and the disappearance and formation of ripples was visualized. It was found that both the disappearance and formation of ripples take place virtually one ripple at a time, thereby demonstrating the highly anisotropic nature of the ripple phase. Furthermore, when a two-component DMPC-DSPC mixture was heated from the ripple phase and into the ripple-phase/fluid-phase coexistence temperature region, the AFM images revealed that several dynamic properties of the ripple phase are important for the melting behavior of the lipid mixture. Onset of melting is observed at grain boundaries between different ripple types and different ripple orientations, and the longer-wavelength metastable ripple phase melts before the shorter-wavelength stable ripple phase. Moreover, it was observed that the ripple phase favors domain growth along the ripple direction and is responsible for creating straight-edged domains with 60 degrees and 120 degrees angles, as reported previously.     

电刺激诱导大鼠海马癫痫电网络神经信息分析

探讨电刺激致海马(hippocampus,HPC)癫痫网络的神经信息特征和M型胆碱能受体阻断剂东莨菪碱(scopolamine)对该信息特征的调制作用。实验用雄性SD大鼠45只,体重150￣250g。急性强直电(60Hz,2s,0.4￣0.6mA)刺激右侧后背HPC(acutetetanizationoftherightposteriordorsalhippocampus,ATPDH),双电极同步记录同侧HPC网络和单个神经元电活动。分析癫痫发作样高频电振荡(ripple)功率谱(powerspec-trum)、尖波连续发放峰间间隔(interpeakinterval,IPI)和单位时间内平均频率(Hz),并同步分析单个神经元放电脉冲间隔(interspikeinterval,ISI)的变化特征。发现:(1)ATPDH诱导的HPC癫痫放电模式主要包括rip-ple和具有稳定频率特征的尖波样连续发放;(2)东莨菪碱(i.p.)可以提前ripple第1组分最大功率(μV2)与单个神经元原发性单位后放电最大ISI出现的时间,对最大ISI的作用更明显;(3)东莨菪碱可以部分再现重复施加ATPDH诱导出现巨大尖波连续发放IPI和神经元放电ISI平行发展特征。结果提示:M胆碱能受体阻断剂东莨菪碱可以同时调制HPC癫痫网络成员电场和细胞的瞬时编码信息;而成员电场ripple功率谱/连续尖波IPI和神经元放电ISI点分布的对比研究,可以用于分析癫痫网络瞬时编码信息和药物生物学效应。     

Evolution of a rippled membrane during phospholipase A2 hydrolysis studied by time-resolved AFM

The sensitivity of phospholipase A(2) (PLA(2)) for lipid membrane curvature is explored by monitoring, through time-resolved atomic force microscopy, the hydrolysis of supported double bilayers in the ripple phase. The ripple phase presents a corrugated morphology. PLA(2) is shown to have higher activity toward the ripple phase compared to the gel phase in 1,2-dimyristoyl-sn-glycero-3-phosphocholine (DMPC) membranes, indicating its preference for this highly curved membrane morphology. Hydrolysis of the stable and metastable ripple structures is monitored for equimolar DMPC/1,2-distearoyl-sn-glycero-3-phosphocholine (DSPC)-supported double bilayers. As shown by high-performance liquid chromatography results, DSPC is resistant to hydrolysis at this temperature, resulting in a more gradual hydrolysis of the surface that leads to a change in membrane morphology without loss of membrane integrity. This is reflected in an increase in ripple spacing, followed by a sudden flattening of the lipid membrane during hydrolysis. Hydrolysis of the ripple phase results in anisotropic holes running parallel to the ripples, suggesting that the ripple phase has strip regions of higher sensitivity to enzymatic attack. Bulk high-performance liquid chromatography measurements indicate that PLA(2) preferentially hydrolyzes DMPC in the DMPC/DSPC ripples. We suggest that this leads to the formation of a flat gel-phase lipid membrane due to enrichment in DSPC. The results point to the ability of PLA(2) for inducing a compositional phase transition in multicomponent membranes through preferential hydrolysis while preserving membrane integrity.     

Ripple-associated high-firing interneurons in the hippocampal CA1 region

By simultaneously recording the activity of individual neurons and field potentials in freely behaving mice, we found two types of interneurons firing at high frequency in the hippocampal CA1 region, which had high correlations with characteristic sharp wave-associated ripple oscillations (100–250 Hz) during slow-wave sleep. The firing of these two types of interneurons highly synchronized with ripple oscillations during slow-wave sleep, with strongly increased firing rates corresponding to individual ripple episodes. Interneuron type I had at most one spike in each sub-ripple cycle of ripple episodes and the peak firing rate was 310±33.17 Hz. Interneuron type II had one or two spikes in each sub-ripple cycle and the peak firing rate was 410±47.61 Hz. During active exploration, their firing was phase locked to theta oscillations with the highest probability at the trough of theta wave. Both two types of interneurons increased transiently their firing rates responding to the startling shake stimuli. The results showed that these two types of high-frequency interneurons in the hippocampal CA1 region were involved in the modulation of the hippocampal neural network during different states.     

Dynamics of appearance and disappearance of the ripple structure in multilamellar liposomes of dipalmitoylphosphatidylcholine

The physical properties of the pretransition (P beta'----L beta') of dipalmitoylphosphatidylcholine liposomes were investigated using freeze-fracture electron microscopy. The kinetics of pretransition examined in the previous paper using TEMPO spin probe (Tsuchida, K., et al. (1985) Biochim. Biophys. Acta 812, 249-254) was extensively studied by observing the ripple structures in the freeze-fractured surfaces at different time intervals. When the temperature is decreased from 38 degrees C to 30 degrees C, the ripple structure disappears in the following steps. The intervals between ripples begin to expand with the decrease of ripple density upon the temperature shift, and this process continues for several tens minutes. Then, each ripple disappears gradually and changes into a completely smooth surface at 3 h after the temperature shift. The comparison of relaxation times between the previous ESR measurement and the present experiment suggests that the fast relaxation observed in the previous study corresponds to the expansion of the intervals between ripples. On the other hand, the ripple structure of regular intervals appears rapidly in some places and then spreads over the whole area of fractured surface when the temperature is increased from 23 degrees C to 35 degrees C. The results obtained in this work and the previous ESR work strongly suggest that the formation and disappearance of ripple structure is closely related to the relaxation processes near the pretransition temperature.     

Lipid-cholesterol interactions in the P beta' phase. Application of a statistical mechanical model.

We describe a statistical mechanical model for lipid-cholesterol mixtures in the P beta' (ripple) phase of lipid bilayers. The model is a simple extension of an earlier model for the ripple phase in pure lipid bilayers. The extension consists of adding a degree of freedom to allow for the occupation of underlying lattice sites by cholesterol molecules, and adding a lipid-cholesterol interaction term to the model Hamiltonian. The interaction term was constructed based on numerical calculations of lipid-cholesterol energies for several different packing juxtapositions of the two molecules. Other than the lipid-cholesterol interactions, the extended model uses the same parameter set as the earlier model, so that comparison of the properties of the extended model with experimental data serves as a test of the validity of the original model. Properties of the model were calculated using the Monte Carlo method. Results are displayed as snapshots of the ripple configurations at different cholesterol concentrations. The spacing of the ripples increases with increasing cholesterol concentration and the rate of increase compares very well with experimental data. The success of this model supports the conclusion drawn earlier that frustration arising from anisotropic packing interactions is responsible for the ripple phase in lipid bilayers. In the extended model these packing interactions are responsible for the selective partitioning of cholesterol in the regions between the ripples.     

Ripple-associated high-firing interneurons in the hippocampal CA1 region

By simultaneously recording the activity of individual neurons and field potentials in freely behaving mice, we found two types of interneurons firing at high frequency in the hippocampal CA1 region, which had high correlations with characteristic sharp wave-associated ripple oscillations (100―250 Hz) during slow-wave sleep. The firing of these two types of interneurons highly synchronized with ripple oscillations during slow-wave sleep, with strongly increased firing rates corresponding to individual ripple episodes. Interneuron type I had at most one spike in each sub-ripple cycle of ripple episodes and the peak firing rate was 310±33.17 Hz. Interneuron type II had one or two spikes in each sub-ripple cycle and the peak firing rate was 410±47.61 Hz. During active exploration, their firing was phase locked to theta oscillations with the highest probability at the trough of theta wave. Both two types of interneurons increased transiently their firing rates responding to the startling shake stimuli. The results showed that these two types of high-frequency interneurons in the hippocampal CA1 region were involved in the modulation of the hippocampal neural network during different states.     

Slow gamma takes the reins in replay

The mechanisms supporting hippocampal memory reactivation are puzzling. Reactivation occurs during ripple oscillations, yet ripples are not coordinated across regions. In this issue of Neuron, Carr et?al. (2012) report that another oscillation, slow gamma, coordinates memory reactivation across the hippocampal network.     

Hippocampal ripples and memory consolidation

During slow wave sleep and quiet wakefulness, the hippocampus generates high frequency field oscillations (ripples) during which pyramidal neurons replay previous waking activity in a temporally compressed manner. As a result, reactivated firing patterns occur within shorter time windows propitious for synaptic plasticity within the hippocampal network and in downstream neocortical structures. This is consistent with the long-held view that ripples participate in strengthening and reorganizing memory traces, possibly by mediating information transfer to neocortical areas. Recent studies have confirmed that ripples and associated neuronal reactivations play a causal role in memory consolidation during sleep and rest. However, further research will be necessary to better understand the neurophysiological mechanisms of memory consolidation, in particular the selection of reactivated assemblies, and the functional specificity of awake ripples.     

Induction of coordinated movement of Myxococcus xanthus cells.

Rhythmically advancing waves of cells, called ripples, arise spontaneously during the aggregation of Myxococcus xanthus into fruiting bodies. Extracts prepared by washing rippling cells contain a substance that will induce quiescent cells to ripple. Three lines of evidence indicate that murein (peptidoglycan) is the ripple-inducing substance in the extracts. First, ripple-inducing activity is associated with the cell envelope of sonically disrupted M. xanthus cells. Second, whole cells, cell extracts, or purified murein from a variety of different bacteria are capable of inducing ripples. In contrast, extracts prepared from Methanobacterium spp. which contain pseudomurein instead of typical bacterial murein fail to induce ripples. Third, four components of M. xanthus murein, N-acetylglucosamine, N-acetylmuramic acid, diaminopimelate, and D-alanine, are able to induce ripples. Ripples produced by aggregating cells have a wavelength of 45 micrometers and a maximum velocity of 2 micrometers/min. Both of the multigene systems that control gliding motility appear to be required for rippling, and all known mutations at the spoC locus eliminate both rippling and sporulation.     

Persistence at low temperature of the P beta' ripple in dipalmitoylphosphatidylcholine multilamellar vesicles containing either glycosphingolipids or cholesterol

The disappearance and reappearance of the P beta' ripple in multilamellar liposomes of dipalmitoylphosphatidylcholine (DPPC) has been examined by freeze-etch electron microscopy. The presence of less than 10 mol% of various glycosphingolipids or cholesterol in the liposomes markedly increases the time required for ripple disappearance when the vesicles are cooled from 38 degrees C to 30 degrees C, as compared to the pure phospholipid. Once the ripples have begun to disappear in the two-component vesicles, they do not uniformly reappear until the system is heated above the main transition of DPPC and allowed to cool into the pretransition region. These results suggest that the long time for ripple disappearance in the two-component systems reflects a slow molecular reorganization process which occurs when the systems are forced to change from the P beta' gel to the L beta' gel by a temperature downshift.     

Spectrotemporal Response Properties of Core Auditory Cortex Neurons in Awake Monkey

So far, most studies of core auditory cortex (AC) have characterized the spectral and temporal tuning properties of cells in non-awake, anesthetized preparations. As experiments in awake animals are scarce, we here used dynamic spectral-temporal broadband ripples to study the properties of the spectrotemporal receptive fields (STRFs) of AC cells in awake monkeys. We show that AC neurons were typically most sensitive to low ripple densities (spectral) and low velocities (temporal), and that most cells were not selective for a particular spectrotemporal sweep direction. A substantial proportion of neurons preferred amplitude-modulated sounds (at zero ripple density) to dynamic ripples (at non-zero densities). The vast majority (>93%) of modulation transfer functions were separable with respect to spectral and temporal modulations, indicating that time and spectrum are independently processed in AC neurons. We also analyzed the linear predictability of AC responses to natural vocalizations on the basis of the STRF. We discuss our findings in the light of results obtained from the monkey midbrain inferior colliculus by comparing the spectrotemporal tuning properties and linear predictability of these two important auditory stages.     

Ripples and the formation of anisotropic lipid domains: imaging two-component supported double bilayers by atomic force microscopy

Direct visualization of the fluid-phase/ordered-phase domain structure in mica-supported bilayers composed of 1,2-dimyristoyl-sn-glycero-3-phosphocholine/1,2-distearoyl-sn-glycero-3-phosphocholine mixtures is performed with atomic force microscopy. The system studied is a double bilayer supported on a mica surface in which the top bilayer (which is not in direct contact with the mica) is visualized as a function of temperature. Because the top bilayer is not as restricted by the interactions with the surface as single supported bilayers, its behavior is more similar to a free-standing bilayer. Intriguing straight-edged anisotropic fluid-phase domains were observed in the fluid-phase/ordered-phase coexistence temperature range, which resemble the fluid-phase/ordered-phase domain patterns observed in giant unilamellar vesicles composed of such phospholipid mixtures. With the high resolution provided by atomic force microscopy, we investigated the origin of these anisotropic lipid domain patterns, and found that ripple phase formation is directly responsible for the anisotropic nature of these domains. The nucleation and growth of fluid-phase domains are found to be directed by the presence of ripples. In particular, the fluid-phase domains elongate parallel to the ripples. The results show that ripple phase formation may have implications for domain formation in biological systems.     

Hippocampal Sharp Wave/Ripples during Sleep for Consolidation of Associative Memory

The beneficial effect of sleep on memory has been well-established by extensive research on humans, but the neurophysiological mechanisms remain a matter of speculation. This study addresses the hypothesis that the fast oscillations known as ripples recorded in the CA1 region of the hippocampus during slow wave sleep (SWS) may provide a physiological substrate for long term memory consolidation. We trained rats in a spatial discrimination task to retrieve palatable reward in three fixed locations. Hippocampal local field potentials and cortical EEG were recorded for 2 h after each daily training session. There was an increase in ripple density during SWS after early training sessions, in both trained rats and in rats randomly rewarded for exploring the maze. In rats learning the place -reward association, there was a striking further significant increase in ripple density correlated with subsequent improvements in behavioral performance as the rat learned the spatial discrimination aspect of the task. The results corroborate others showing an experience-dependent increase in ripple activity and associated ensemble replay after exploratory activity, but in addition, for the first time, reveal a clear further increase in ripple activity related to associative learning based on spatial discrimination.     

Place-selective firing of CA1 pyramidal cells during sharp wave/ripple network patterns in exploratory behavior

We observed sharp wave/ripples (SWR) during exploration within brief (<2.4 s) interruptions of or during theta oscillations. CA1 network responses of SWRs occurring during exploration (eSWR) and SWRs detected in waking immobility or sleep were similar. However, neuronal activity during eSWR was location dependent, and eSWR-related firing was stronger inside the place field than outside. The eSPW-related firing increase was stronger than the baseline increase inside compared to outside, suggesting a "supralinear" summation of eSWR and place-selective inputs. Pairs of cells with similar place fields and/or correlated firing during exploration showed stronger coactivation during eSWRs and subsequent sleep-SWRs. Sequential activation of place cells was not required for the reactivation of waking co-firing patterns; cell pairs with symmetrical cross-correlations still showed reactivated waking co-firing patterns during sleep-SWRs. We suggest that place-selective firing during eSWRs facilitates initial associations between cells with similar place fields that enable place-related ensemble patterns to recur during subsequent sleep-SWRs.     

Diffraction of X-rays by rippled phosphatidylcholine bilayers

X-ray diffraction patterns have been obtained from the rippled phases of two pure synthetic phosphatidylcholines (dimyristoyl and dipalmitoyl) and mixtures of these phospholipids and cholesterol arranged in oriented multibilayer stacks. These show for the first time in an oriented specimen, a two-dimensionally resolved pattern near the meridian. For example, in pure dipalmitoylphosphatidylcholine the unit cell is two-dimensional and oblique. The ripples have a wavelength of 165.3 Å and are at least 1000 Å wide in the direction perpendicular to this, in the plane of the bilayer. The shape of the ripple is more complex than simply sinusoidal.     

Small pits associated with renilla (Cnidaria: Pennatulacea) on a modern low‐energy sandflat,Kiawah Island,South Carolina,U.S.A.

Small, shallow circular pits containing the Atlantic sea pansy, Renilla reniformis, were fairly common at one locality on the lower foreshore of Kiawah Island in June, 1997. Many of the pits were positioned on the stoss side of sand ripples; the organisms were oriented with their bilateral plane of symmetry essentially parallel to ripple crests. If preserved as concave epireliefs or convex hyporeliefs on bedding surfaces, such pits would be difficult not only to attribute to a trace producer or traditional ethologic category, but to identify as trace fossils in the first place.