Hai-Qing Gong

Firing rates and dynamic correlated activities of ganglion cells both contribute to retinal information processing.

In the present study, the electrical activities of paired retinal ganglion cells, under full field light stimuli with a variety of chromatic configurations, were recorded from a small functioning piece of retina using multi-electrode array (MEA). Neurons that had increased firings at light-ON and -OFF transients and did not show color-opponent properties were investigated. Single neuronal analysis showed that firing rate of each individual neuron was dependent on the intensity of illumination. Multi-unit analyses revealed that adjacent neurons often fired in synchrony in response to light stimulation. However, in some cases, the strength of correlation between the paired neurons was higher when the retina was exposed to red or green light, and the correlation was attenuated when yellow or white light was given. This seems to suggest that the ensemble activity of non-color-opponent ganglion cells might partly participate in color-information processing, with the red- and green-pathway inputs influencing each other. Such arrangement reflects principle of parsimony: the firing rates of single neuron represent the luminance intensity, and the correlated activities may tell the brain about the color information.

Luminance adaptation increased the contrast sensitivity of retinal ganglion cells.

In the present study, the activity changes of chicken retinal ganglion cells in response to light stimuli with defined contrast were investigated, in the presence of various levels of sustained background illumination. Following a step increase of light illumination, the firing rate of most retinal ganglion cells increased abruptly, and then decreased to a steady-state level with a much lower firing rate during the sustained application of light. However, when a test flash was applied, which superimposed the prolonged background illumination, an increased firing rate was observed. Moreover, the neuron firing rate was increased to a greater extent when the intensity of the background illumination was higher. This may suggest that the neuron sensitivity can be modified by the background illumination level, although the neuron firing rate was reduced during sustained illumination.

Visual pattern recognition based on spatio-temporal patterns of retinal ganglion cells’ activities

Neural information is processed based on integrated activities of relevant neurons. Concerted population activity is one of the important ways for retinal ganglion cells to efficiently organize and process visual information. In the present study, the spike activities of bullfrog retinal ganglion cells in response to three different visual patterns (checker-board, vertical gratings and horizontal gratings) were recorded using multi-electrode arrays. A measurement of subsequence distribution discrepancy (MSDD) was applied to identify the spatio-temporal patterns of retinal ganglion cells’ activities in response to different stimulation patterns. The results show that the population activity patterns were different in response to different stimulation patterns, such difference in activity pattern was consistently detectable even when visual adaptation occurred during repeated experimental trials. Therefore, the stimulus pattern can be reliably discriminated according to the spatio-temporal pattern of the neuronal activities calculated using the MSDD algorithm.

Spatiotemporal dynamics of high-K + -induced epileptiform discharges in hippocampal slice and the effects of valproate

The epileptic seizure is a dynamic process involving a rapid transition from normal activity to a state of hypersynchronous neuronal discharges. Here we investigated the network properties of epileptiform discharges in hippocampal slices in the presence of high K+ concentration (8.5 mmol/L) in the bath, and the effects of the anti-epileptic drug valproate (VPA) on epileptiform discharges, using a microelectrode array. We demonstrated that epileptiform discharges were predominantly initiated from the stratum pyramidale layer of CA3a-b and propagated bi-directionally to CA1 and CA3c. Disconnection of CA3 from CA1 abolished the discharges in CA1 without disrupting the initiation of discharges in CA3. Further pharmacological experiments showed that VPA at a clinically relevant concentration (100 μmol/L) suppressed the propagation speed but not the rate or duration of high-K+-induced discharges. Our findings suggest that pacemakers exist in the CA3a-b region for the generation of epileptiform discharges in the hippocampus. VPA reduces the conduction of such discharges in the network by reducing the propagation speed.

Influence of GABAergic inhibition on concerted activity between the ganglion cells

In this study, the spike discharges of one subtype of bullfrog retinal ganglion cells (dimming detectors) in response to repetitive full field light-OFF stimuli were recorded using multi-electrode arrays. Two different types of concerted activity (precise synchronization and correlated activity) could be distinguished. The nearby cells with overlapped receptive field areas often fired in synchrony, whereas the correlated activity was mainly observed from remote cell pairs with separated receptive fields. After the bicuculline application, the strength of the synchronized activity was increased whereas that of the correlated activity was decreased. These results suggest that the activation of GABAA-receptor-mediated inhibitory pathways differentially modulates the concerted firing of the ganglion cells.

Involvement of Thalamus in Initiation of Epileptic Seizures Induced by Pilocarpine in Mice

Studies have suggested that thalamus is involved in temporal lobe epilepsy, but the role of thalamus is still unclear. We obtained local filed potentials (LFPs) and single-unit activities from CA1 of hippocampus and parafascicular nucleus of thalamus during the development of epileptic seizures induced by pilocarpine in mice. Two measures, redundancy and directionality index, were used to analyze the electrophysiological characters of neuronal activities and the information flow between thalamus and hippocampus. We found that LFPs became more regular during the seizure in both hippocampus and thalamus, and in some cases LFPs showed a transient disorder at seizure onset. The variation tendency of the peak values of cross-correlation function between neurons matched the variation tendency of the redundancy of LFPs. The information tended to flow from thalamus to hippocampus during seizure initiation period no matter what the information flow direction was before the seizure. In some cases the information flow was symmetrically bidirectional, but none was found in which the information flowed from hippocampus to thalamus during the seizure initiation period. In addition, inactivation of thalamus by tetrodotoxin (TTX) resulted in a suppression of seizures. These results suggest that thalamus may play an important role in the initiation of epileptic seizures.

Synaptic contribution of Ca2+-permeable and Ca2+-impermeable AMPA receptors on isolated carp retinal horizontal cells and their modulation by Zn2+

Ca(2+)-permeable and Ca(2+)-impermeable AMPA receptors are co-expressed on carp retinal horizontal cells. In the present study, we examined the synaptic contribution and Zn(2+) modulatory effect of these two AMPA receptor subtypes using whole-cell patch clamp technique. Specific Ca(2+)-permeable AMPA receptor antagonist (1-naphthyl acetyl spermine, NAS) and selective Ca(2+)-impermeable AMPA receptor blocker (pentobarbital, PB) were used to separate the glutamate-response in isolated H1 horizontal cell mediated by these two subtypes of AMPA receptors respectively. Application of 100 microM NAS substantially suppressed the current elicited by 3 mM glutamate and the remaining NAS-insensitive component was completely blocked by application of 100 microM PB. In addition, Zn(2+) had dual effects on Ca(2+)-permeable AMPA receptor-mediated current: at low concentration (10 microM), Zn(2+) potentiated the current, but at higher concentrations (100 and 1000 microM), Zn(2+) reduced the current in a dose-dependent manner. However, Zn(2+) (10, 100 and 1000 microM) failed to modulate the NAS-insensitive current mediated by Ca(2+)-impermeable AMPA receptors. Overall, our results suggest that Ca(2+)-permeable AMPA receptors contribute more to the cells glutamate-response than Ca(2+)-impermeable AMPA receptors. Furthermore, Zn(2+) has dual effects on the Ca(2+)-permeable AMPA receptor activity without affecting Ca(2+)-impermeable AMPA receptors.

NMDA modulation of GABA transporter current in carp retinal horizontal cells

In the present study, the modulatory effect of NMDA on GABA transporter current was investigated on enzymatically isolated horizontal cells of carp retina. After application of NMDA (0.1 mM) for 50 s, the GABA transporter current elicited by GABA (1 mM) was decreased to 78.07+/-3.10% (n=5) of the control level. When the extracellular Ca(2+) was removed from the Ringers solution, the NMDA inhibitory effect on the GABA transporter current was eliminated. The suppression effect could be attenuated when the Ca(2+) release and Ca(2+) uptake of intracellular Ca(2+) store were blocked after the cell had been pre-incubated with 20 muM ryanodine plus 2 muM thapsigargin. Application of 10 mM BAPTA in intracellular solution also suppressed the NMDA modulation of GABA transporters. These results suggest that the activation of NMDA receptors inhibits GABA transporter-mediated current by affecting Ca(2+) processes in the retinal horizontal cells.

Spatial and temporal correlations of spike trains in frog retinal ganglion cells

For a neuron, firing activity can be in synchrony with that of others, which results in spatial correlation; on the other hand, spike events within each individual spike train may also correlate with each other, which results in temporal correlation. In order to investigate the relationship between these two phenomena, population neurons’ activities of frog retinal ganglion cells in response to binary pseudo-random checker-board flickering were recorded via a multi-electrode recording system. The spatial correlation index (SCI) and temporal correlation index (TCI) were calculated for the investigated neurons. Statistical results showed that, for a single neuron, the SCI and TCI values were highly related—a neuron with a high SCI value generally had a high TCI value, and these two indices were both associated with burst activities in spike train of the investigated neuron. These results may suggest that spatial and temporal correlations of single neuron’s spiking activities could be mutually modulated; and that burst activities could play a role in the modulation. We also applied models to test the contribution of spatial and temporal correlations for visual information processing. We show that a model considering spatial and temporal correlations could predict spikes more accurately than a model does not include any correlation.

Caffeine-Induced Ca2+ Oscillations in Type I Horizontal Cells of the Carp Retina and the Contribution of the Store-Operated Ca2+ Entry Pathway

The mechanisms of release, depletion, and refilling of endoplasmic reticulum (ER) Ca2+ were investigated in type I horizontal cells of the carp retina using a fluo-3-based Ca2+ imaging technique. Exogenous application of caffeine, a ryanodine receptor agonist, induced oscillatory intracellular free Ca2+ concentration ([Ca2+]i) responses in a duration- and concentration-dependent manner. In Ca2+-free Ringer’s solution, [Ca2+]i transients could also be induced by a brief caffeine application, whereas subsequent caffeine application induced no [Ca2+]i increase, which implied that extracellular Ca2+ was required for ER refilling, confirming the necessity of a Ca2+ influx pathway for ER refilling. Depletion of ER Ca2+ by thapsigargin triggered a Ca2+ influx which could be blocked by the store-operated channel inhibitor 2-APB, which proved the existence of the store-operated Ca2+ entry pathway. Taken together, these results suggested that after being depleted by caffeine, the ER was replenished by Ca2+ influx via store-operated channels. These results reveal the fine modulation of ER Ca2+ signaling, and the activation of the store-operated Ca2+ entry pathway guarantees the replenishment of the ER so that the cell can be ready for response to the subsequent stimulus.