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Objective. Ultrasound modulates the firing activity of retinal ganglion cells (RGCs), but the effects of lower-frequency, lower-intensity ultrasound on RGCs and underlying mechanism(s) remain poorly understood. This study aims to address these questions. Approach. Multi-electrode recordings were used in this study to record the firing sequences of RGCs in isolated mouse retinas. RGCs’ background firing activities as well as their light responses were recorded with or without ultrasound stimulation. Cross-correlation analyses were performed to investigate the possible cellular/circuitry mechanism(s) underlying ultrasound modulation. Main results. It was found that ultrasound stimulation of isolated mouse retina enhanced the background activity of ON-RGCs and OFF-RGCs. In addition, background ultrasound stimulation shortened the light response latency of both ON-RGCs and OFF-RGCs, while enhancing part of the RGCs’ (both ON- and OFF-subtypes) light response and decreasing that of the others. In some ON-OFF RGCs, the ON- and OFF-responses of an individual cell were oppositely modulated by the ultrasound stimulation, which suggests that ultrasound stimulation does not necessarily exert its effect directly on RGCs, but rather via its influence on other type(s) of cells. By analyzing the cross-correlation between the firing sequences of RGC pairs, it was found that concerted activity occurred during ultrasound stimulation differed from that occurred during light stimulation, in both spatial and temporal aspects. These results suggest that the cellular circuits involved in ultrasound- and light-induced concerted activities are different and glial cells may be involved in the circuit in response to ultrasound. Significance. These findings demonstrate that ultrasound affects neuronal background activity and light responsiveness, which are critical for visual information processing. These results may also imply a hitherto unrecognized role of glial cell activation in the bidirectional modulation effects of RGCs and may be critical for the nervous system.

Localization of the epileptogenic zone (EZ) is essential for the successful surgical treatment of medically intractable epilepsy. In the present study, stereo-EEG (SEEG) recordings were obtained from seven patients underwent presurgical evaluation for treatment of intractable epilepsy. Partial directed coherence (PDC) analysis was applied to construct peri-ictal effective connectivity networks. The graphic measures, in-degree, out-degree and betweenness centrality, were evaluated to localize the EZ. A receiver operating characteristic (ROC) analysis was used to quantify the localization accuracy. We found that the in-degree coincided well with the EZ identified by epileptologists' visual inspection in all seven patients who had a significant improvement in seizure outcomes, however, the other two measures were effective only in some cases. Furthermore, in all seven patients the electrode contact with the highest in-degree was always located within the EZ identified by epileptologists' visual inspection. These results indicate that the graph theory is an effective method to localize the EZ when suitable graphic measures were chosen. Furthermore, the in-degree was the most effective measure among the three graphic measures in localizing the EZ when the PDC method was used.

Oscillatory activity of retinal ganglion cell (RGC) has been observed in various species. It was reported such oscillatory activity is raised within large neural network and involved in retinal information coding. In the present research, we found an oscillation-like activity in ON–OFF RGC of bullfrog retina, and studied the mechanisms underlying the ON and OFF activities respectively. Pharmacological experiments revealed that the oscillation-like activity patterns in both ON and OFF pathways were abolished by GABA receptor antagonists, indicating GABAergic inhibition is essential for generating them. At the meantime, such activities in the ON and OFF pathways showed different responses to several other applied drugs. The oscillation-like pattern in the OFF pathway was abolished by glycine receptor antagonist or gap junction blocker, whereas that in the ON pathway was not affected. Furthermore, the blockade of the ON pathway by metabotropic glutamate receptor agonist led to suppression of the oscillation-like pattern in the OFF pathway. These results suggest that the ON pathway has modulatory effect on the oscillation-like activity in the OFF pathway. Therefore, the mechanisms underlying the oscillation-like activities in the ON and OFF pathways are different: the oscillation-like activity in the ON pathway is likely caused by GABAergic amacrine cell network, while that in the OFF pathway needs the contributions of GABAergic and glycinergic amacrine cell network, as well as gap junction connections.

In the daily life, we perceive the world around us by integrating multiple sensory cues (visual, auditory, olfactory, gustatory, tactile, vestibular and proprioceptive) to create a coherent, reliable representation that allows us to interact meaningfully with the environment. The integration of different sensory information is necessary for our perception, motor transformation, decision making, learning and memory. In the past decades, many interdisciplinary researchers have been attracted to the field of multisensory research, and tremendous advances have been made in this field. We review the researches on multisensory integration during self-motion perception in the past decades from the candidate areas, the integration principles and the neural correlation of the behaviors, with the intention to provide a comprehensive source for those interested in understanding the neural substrates for multisensory integration. Meanwhile, we also provide a prospect for the future research in this field.

Oscillations in intracellular free Ca(2+) concentration ([Ca(2+)]i) have been observed in a variety of cell types. In the present study, we constructed a mathematical model to simulate the caffeine-induced [Ca(2+)]i oscillations based on experimental data obtained from isolated type I horizontal cell of carp retina. The results of model analysis confirm the notion that the caffeine-induced [Ca(2+)]i oscillations involve a number of cytoplasmic and endoplasmic Ca(2+) processes that interact with each other. Using this model, we evaluated the importance of store-operated channel (SOC) in caffeine-induced [Ca(2+)]i oscillations. The model suggests that store-operated Ca(2+) entry (SOCE) is elicited upon depletion of the endoplasmic reticulum (ER). When the SOC conductance is set to 0, caffeine-induced [Ca(2+)]i oscillations are abolished, which agrees with the experimental observation that [Ca(2+)]i oscillations were abolished when SOC was blocked pharmacologically, verifying that SOC is necessary for sustained [Ca(2+)]i oscillations.

Retinal ganglion cells (RGCs) exhibit adaptive changes in response to sustained light stimulation, which include decrease in firing rate, tendency to shrink in receptive field (RF) size and reduction in synchronized activities. Gamma-aminobutyric acid-ergic (GABAergic) pathway is an important inhibitory pathway in retina. In the present study, the effects of GABAergic pathway on the contrast adaptation process of bullfrog RGCs were studied using multi-electrode recording technique. It was found that the application of bicuculline (BIC), a gamma-aminobutyric acid A (GABAA) receptor antagonist, caused a number of changes in the RGCs’ response characteristics, including attenuation in adaptation-dependent firing rate decrease and the adaptation-dependent weakening in synchronized activities between adjacent neuron-pairs, whereas intensified the adaptation-dependent RF size shrinkage. These results suggest that GABAA receptors are involved in the modulation of the firing activity and synchronized activities in contrast adaptation process of the RGCs, whereas the adaptation-related RF property changes involve more complicated mechanisms.

Studies have reported that the subiculum is one origin of interictal-like discharges in adult patients with temporal lobe epilepsy; however, whether the subiculum represents a site of ictogenesis for neonatal seizures remains unclear. In this study, multi-electrode recording techniques were used to record epileptiform discharges induced by low-Mg2+ or high-K+ artificial cerebrospinal fluid in neonatal mouse hippocampal slices, and the spatiotemporal dynamics of the epileptiform discharges were analyzed. The Na+-K+-2Cl- cotransporter 1 (NKCC1) blocker, bumetanide, was applied to test its effect upon epileptiform discharges in low-Mg2+ model. The effect of N-methyl-D-aspartate receptors (NMDARs) antagonist, D-AP5, upon the epileptiform discharges in high-K+ model was examined. We found that the neonatal subiculum not only relayed epileptiform discharges emanating from the hippocampus proper, but also initiated epileptiform discharges (interictal- and ictal-like discharges) independently. The latency to onset of the first epileptiform discharge initiated in the subiculum was similar to that initiated in the hippocampus proper. Bumetanide efficiently blocked seizures in the neonatal hippocampus proper, but was less effectively in suppressing seizures initiated in the subiculum. In high-K+ model, D-AP5 was more effective in blocking seizures initiated in the subiculum than that initiated in the hippocampus proper. Furthermore, Western blotting analysis showed that NKCC1 expression was lower in the subiculum than that in the hippocampus proper, whereas the expression of NMDAR subunits, NR2A and NR2B, was higher in the subiculum than that in the hippocampus proper. Our results revealed that the subiculum was a potential site of ictogenesis in neonatal seizures and possessed similar seizure susceptibility to the hippocampus proper. GABAergic excitation resulting from NKCC1 may play a less dominant role during ictogenesis in the subiculum than that in the hippocampus proper. The subicular ictogenesis may be related to the glutamatergic excitation mediated by NMDARs.

A 'trial-to-trial adaptation' of bullfrog retinal ganglion cells in response to a repetitive light stimulus was investigated in the present study. Using the multielectrode recording technique, we studied the trial-to-trial adaptive properties of ganglion cells and explored the activity of population neurons during this adaptation process. It was found that the ganglion cells adapted with different degrees: their firing rates were decreased in different extents from early-adaptation to late-adaptation stage, and this was accompanied by a decrease in cross-correlation strength. In addition, adaptation behavior was different for ON-response and OFF-response, which implied that the mechanism of the trial-to-trial adaptation might involve bipolar cells and/or their synapses with other neurons and the stronger adaptation in the ganglion cells' OFF-responses might reflect the requirement to avoid possible saturation in the OFF circuit.

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.

Stimulus duration is an important feature of visual stimulation. In the present study, response properties of bullfrog ON-OFF retinal ganglion cells (RGCs) in exposure to different visual stimulus durations were studied. By using a multi-electrode recording system, spike discharges from ON-OFF RGCs were simultaneously recorded, and the cells' ON and OFF responses were analyzed. It was found that the ON response characteristics, including response latency, spike count, as well as correlated activity and relative latency between pair-wise cells, were modulated by different light OFF intervals, while the OFF response characteristics were modulated by different light ON durations. Stimulus information carried by the ON and OFF responses was then analyzed, and it was found that information about different light ON durations was more carried by transient OFF response, whereas information about different light OFF intervals were more carried by transient ON response. Meanwhile, more than 80 % information about stimulus durations was carried by firing rate. These results suggest that ON-OFF RGCs are sensitive to different stimulus durations, and they can efficiently encode the information about visual stimulus duration by firing rate.

Epilepsy is growingly considered as a brain network disorder. In this study, epileptiform discharges were induced by low-Mg2+ in mouse entorhinal cortex-hippocampal slices, and recorded with a micro-electrode array. Dynamic effective network connectivity was constructed by calculating the time-variant partial directed coherence (tvPDC) of signals. We proposed a novel approach to track the state transitions of epileptic networks over time, and characterized the network topology by using graphical measures. We found that the hub nodes with high degrees in the network coincided with the epileptogenic zone in previous electrophysiological findings. Two consecutive states with distinct network topologies were identified during the ictal-like discharges. The small-worldness remained at a low level at the first state but increased significantly at the second state. Our results indicate the ability of tvPDC to capture the causal interaction between multi-channel signals important in indentifying the epileptogenetic zone. Moreover, the evolution of network states extends our knowledge of the network drivers for the initiation and maintenance of ical activity, and suggests the practical value of our network clustering approach.

Objectives: Accurate localization of epileptogenic zones (EZs) is essential for successful surgical treatment of refractory focal epilepsy. The aim of the present study is to investigate whether a dynamic network connectivity analysis based on stereo-electroencephalography (SEEG) signals is effective in localizing EZs. Methods: SEEG data were recorded from seven patients who underwent presurgical evaluation for the treatment of refractory focal epilepsy and for whom the subsequent resective surgery gave a good outcome. A time-variant multivariate autoregressive model was constructed using a Kalman filter, and the time-variant partial directed coherence was computed. This was then used to construct a dynamic directed network model of the epileptic brain. Three graph measures (in-degree, out-degree, and betweenness centrality) were used to analyze the characteristics of the dynamic network and to find the important nodes in it. Results: In all seven patients, the indicative EZs localized by the in-degree and the betweenness centrality were highly consistent with the clinically diagnosed EZs. However, the out-degree did not indicate any significant differences between nodes in the network. Conclusions: In this work, a method based on ictal SEEG signals and effective connectivity analysis localized EZs accurately. The results suggest that the in-degree and betweenness centrality may be better network characteristics to localize EZs than the out-degree.

Objective It has been shown that low-intensity ultrasound (LIUS) can suppress seizures in some laboratory studies. However, the mechanism of the suppression effect of LIUS remains unclear. The goal of this study is to investigate the modulation effects of focused LIUS on epileptiform discharges in mouse hippocampal slices as well as the underlying mechanism. Approach Epileptiform discharges in hippocampal slices of 8 d-old mice were induced by low-Mg2+ artificial cerebrospinal fluid and recorded by a micro-electrode array in vitro. LIUS was delivered to hippocampal slices to investigate its modulation effects on epileptiform discharges. Pharmacological experiments were conducted to study the mechanism of the modulation effects. Main results LIUS suppressed the amplitude, rate and duration of ictal discharges. For inter-ictal discharges, LIUS suppressed the amplitude but facilitated the rate. LIUS suppressed the spontaneous spiking activities of pyramidal neurons in CA3, and the suppression effect was eliminated by Kaliotoxin. The suppression effect of LIUS on epileptiform discharges was weakened when the perfusion was mixed with Kaliotoxin. Significance Those findings demonstrate that LIUS suppresses the epileptiform discharges in 8 d-old mouse hippocampal slices and that its suppression effect can mainly attributed to the activation of mechanosensitive Kv1.1 channels.

Neuronal responses to prolonged stimulation attenuate over time. Here, we ask a fundamental question: is adaptation a simple process for the neural system during which sustained input is ignored, or is it actually part of a strategy for the neural system to adjust its encoding properties dynamically? After simultaneously recording the activities of a group of bullfrog's retinal ganglion cells (dimming detectors) in response to sustained dimming stimulation, we applied a combination of information analysis approaches to explore the time-dependent nature of information encoding during the adaptation. We found that at the early stage of the adaptation, the stimulus information was mainly encoded in firing rates, whereas at the late stage of the adaptation, it was more encoded in neural correlations. Such a transition in encoding properties is not a simple consequence of the attenuation of neuronal firing rates, but rather involves an active change in the neural correlation strengths, suggesting that it is a strategy adopted by the neural system for functional purposes. Our results reveal that in encoding a prolonged stimulation, the neural system may utilize concerted, but less active, firings of neurons to encode information.

Synchronized activities among retinal ganglion cells (RGCs) via gap junctions can be increased by exogenous dopamine (DA). During DA application, single neurons' firing activities become more synchronized with its adjacent neighbors. One intriguing question is how the enhanced spatial synchronization alters the temporal firing structure of single neurons. In the present study, firing activities of bullfrog's dimming detectors in response to binary pseudo-random checker-board flickering were recorded via a multi-channel recording system. DA was applied in the retina to modulate synchronized activities between RGCs, and the effect of DA on firing activities of single neurons was examined. It was found that, during application of DA, synchronized activities between single neuron and its neighboring neurons was enhanced. At the meantime, the temporal structures of single neuron spike train changed significantly, and the temporal correlation in single neuron's response decreased. The pharmacological study results indicated that the activation of D1 receptor might have effects on gap junction permeability between RGCs. Our results suggested that the dopaminergic pathway participated in the modulation of spatial and temporal correlation of RGCs' firing activities, and may exert critical effects on visual information processing in the retina.

In vertebrate visual system, retina is the first stage for visual information processing. Retinal ganglion cells are the only output neurons of the retina, and their firing activities are dependent on visual stimuli. Retinal ganglion cells can effectively encode visual information via various manners, such as firing rate, temporal structure of spike trains, and concerted activity, etc. Adaptation is one of the basic characteristics of the nervous system, which enables retinal neurons to encode stimuli under a wide variety of natural conditions with limited range in their output. This article reviews the recent studies focused on the coding properties and adaptation of retinal ganglion cells. Relevant issues about dynamical adjustment of coding strategies of retinal ganglion cells in response to different visual stimulation, as well as physiological property and function of adaptation are discussed.

In resting human subjects, successive breaths are correlated (12). In order to investigate the relationship between the present breath and previous ones, time-series analysis (autoregressive modelling) has been applied to study the breath-by-breath variations in ventilation during steady breathing under different conditions for different species (4, 8, 9, 10).