Getting a Foothold on Diabetic Foot Disease-Outcomes of a Multidisciplinary Clinical Pathway for Inpatient Diabetic Foot Care: A 17-Year Institutional Review.

INTRODUCTION: Diabetes foot disease (DFD) contributes to poor quality of life, clinical and economic burden. Multidisciplinary diabetes foot teams provide prompt access to specialist teams thereby improving limb salvage. We present a 17-year review of an inpatient multidisciplinary clinical care path (MCCP) for DFD in Singapore. METHODS: This was a retrospective cohort study of patients admitted for DFD and enrolled in our MCCP to a 1700-bed university hospital from 2005 to 2021. RESULTS: There were 9279 patients admitted with DFD with a mean of 545 (±119) admissions per year. The mean age was 64 (±13.3) years, 61% were Chinese, 18% Malay and 17% Indian. There was a higher proportion of Malay (18%) and Indian (17%) patients compared to the country's ethnic composition. A third of the patients had end stage renal disease and prior contralateral minor amputation. There was a reduction in inpatient major lower extremity amputation (LEA) from 18.2% in 2005 to 5.4% in 2021 (odds ratio 0.26, 95% confidence interval 0.16-0.40, P < .001) which was the lowest since pathway inception. Mean time from admission to first surgical intervention was 2.8 days and mean time from decision for revascularization to procedure was 4.8 days. The major-to-minor amputation rate reduced from 1.09 in 2005 to 0.18 in 2021, reflecting diabetic limb salvage efforts. Mean and median length of stay (LOS) for patients in the pathway was 8.2 (±14.9) and 5 (IQR = 3) days, respectively. There was a gradual trend of increase in the mean LOS from 2005 to 2021. Inpatient mortality and readmission rate was stable at 1% and 11%. CONCLUSION: Since the institution of a MCCP, there was a significant improvement in major LEA rate. An inpatient multidisciplinary diabetic foot care path helped to improve care for patients with DFD.

Mechanism of low-frequency, low-intensity ultrasound modulation of the mouse retina.

Objective.Ultrasound has been shown to modulate the activity of retinal ganglion cells (RGCs) in mice, but the mechanism remains poorly understood. This study aims to address this question.Approach.Multi-electrode recordings together with pharmacological methods were used to investigate the possible cellular/circuitry mechanism(s) underlying the neuronal modulation induced by low-frequency (1 MHz), low-intensity (ISPTA0.5 W cm-2) ultrasound stimulation.Main results.We found that ultrasound activated mechanosensitive channels (transient receptor potential vanilloid 4 (TRPV4) channels are involved) in Müller cells, causing the release of glutamate, which acts on the extrasynapticN-methyl-D-aspartate receptors of RGCs, thus leading to the modulation of neuronal activity.Significance.Our results reveal a novel mechanism of low-frequency, low-intensity ultrasound modulation, involving TRPV4 as a mechanosensitive target for ultrasound and glutamate as an essential mediator of neuron-glia communication. These findings also demonstrate that the mechanical-force-mediated pathway is important for retinal signal modulation during visual processes, such as visual accommodation.

Complementary effects of phosphorus supply and planting density on maize growth and phosphorus use efficiency.

Phosphorus (P) supply and planting density regulate plant growth by altering root morphological traits and soil P dynamics. However, the compensatory effects of P supply and planting density on maize (Zea mays L.) growth and P use efficiency remain unknown. In this study, we conducted pot experiments of approximately 60 days to determine the effect of P supply, i.e., no P (CK), single superphosphate (SSP), and monoammonium phosphate (MAP), and different planting densities (low: two plants per pot; and high: four plants per pot) on maize growth. A similar shoot biomass accumulation was observed at high planting density under CK treatment (91.5 g plot-1) and low planting density under SSP treatment (94.3 g plot-1), with similar trends in P uptake, root morphological traits, and arbuscular mycorrhizal colonization. There was no significant difference in shoot biomass between high planting density under SSP (107.3 g plot-1) and low planting density under MAP (105.2 g plot-1); the corresponding P uptake, root growth, and P fraction in the soil showed the same trend. These results suggest that improved P supply could compensate for the limitations of low planting density by regulating the interaction between root morphological traits and soil P dynamics. Furthermore, under the same P supply, the limitations of low planting density could be compensated for by substituting MAP for SSP. Our results indicate that maize growth and P use efficiency could be improved by harnessing the compensatory effects of P supply and planting density to alter root plasticity and soil P dynamics.

Low-frequency, low-intensity ultrasound modulates light responsiveness of mouse retinal ganglion cells.

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.

Synergies in sustainable phosphorus use and greenhouse gas emissions mitigation in China: Perspectives from the entire supply chain from fertilizer production to agricultural use.

Synergies to achieve high phosphorus (P) use efficiency (PUE) and mitigate greenhouse gas (GHG) emissions are critical for developing strategies aimed toward agricultural green development. However, the potential effects of such synergies in the entire P supply chain through optimizing P management in crop production are poorly understood. In this study, a partial life cycle of a GHG emissions model was developed to quantify the P-related GHG emissions in the entire P supply chain in China. Our results showed that 16.3 kg CO2-equivalent (CO2-eq) was produced from the entire P supply chain per unit of P used for grain agriculture (maize, rice, and wheat). P-related GHG emissions in China increased more than five-fold from 1980 (7.2 Tg CO2-eq) to 2018 (44.9 Tg CO2-eq). GHG emissions were found to be strongly associated with the intensity of grain production in China, and they varied considerably across production regions owing to the differences in the P fertilizer production efficiency. Mineral P fertilizer use in crop production was the primary source of P-related GHG emissions. The results suggest that sustainable P management by matching mineral P fertilizer rates and fertilizer types with crop needs can mitigate GHG emissions by 10.8-27.7 Tg (24.0-65.1%). Moreover, this can improve PUE and reduce mineral P input by 0.7-1.4 Tg (24.0-46.0%). These findings highlight that potential synergies between high PUE and low P-related GHG emissions can be achieved via sustainable P management, thereby enhancing green agricultural development in China and other regions worldwide.

Using knowledge-based management for sustainable phosphorus use in China.

Sustainable phosphorus (P) management presents challenges in crop production and environmental protection; the current understanding of chemical P-fertilizer manufacturing, rock phosphate (RP) mining, P loss within supply chains, and strategies to mitigate loss is incomplete because of a fragmented understanding of P in the crop production supply chain. Therefore, we develop a knowledge-based management theoretical framework to analyze P supply chains to explore ways to mitigate China's P crisis. This framework connects upstream P industries and crop production, addressing knowledge gaps and stakeholder involvement. We demonstrate the potential to improve P use efficiency in the supply chain, thereby mitigating the P crisis using optimized P management. Our results showed that P footprint and grain production demand for RP can be reduced without yield penalty using a crop-demand-oriented P supply chain management that integrates P use in crop production, P-fertilizer manufacturing, and RP mining. Food security and P-related environment sustainability can be achieved by sharing responsibility and knowledge among stakeholders.

Toward the sustainable use of mineral phosphorus fertilizers for crop production in China: From primary resource demand to final agricultural use.

Sustainable phosphorus (P) management is crucial to both food security and environmental conservation. The optimization of P input from mineral fertilizers has been advocated as an effective approach to improve P use efficiency. However, strategies for maximizing P use efficiency by linking soil-crop systems and fertilizer types with the P flow, from a whole P supply chain perspective, are lacking. In this study, a meta-analysis and substance flow analysis (SFA) were employed to evaluate the effects of different mineral P fertilizer types on crop yield and P flow from rock phosphate (RP) exploitation to P use in China. Compared to single superphosphate (SSP), triple superphosphate (TSP), and calcium magnesium phosphate (CMP), a significantly higher yield was obtained when diammonium phosphate (DAP) and monoammonium phosphate (MAP) were used 2005 onwards. However, P loss, from RP extraction to application, was 24% higher for DAP and MAP than for SSP, TSP, and CMP. DAP and MAP use led to a 6% larger P footprint than SSP, TSP, and CMP use. The P use efficiency could be improved by 22%, 36%, and 40% in wheat, maize, and rice production, respectively, by integrating the soil-crop system with mineral P fertilizer types, while P loss and P footprint could be reduced by 13% and 17%, respectively. These results indicate that P use efficiency can be significantly improved by integrating mineral P fertilizer types with soil-crop systems, providing an effective approach for RP exploitation to improve P use efficiency and alleviate the overexploitation of RP.

Phosphorus-Use Efficiency Modified by Complementary Effects of P Supply Intensity With Limited Root Growth Space.

Space availability and the maintenance of adequate phosphorus (P) supply in the root zone are essential for achieving high yield and P-use efficiency in maize production by manipulating the root morphology and arbuscular mycorrhizal (AM) fungi colonization. A major trade-off exists between root growth and AM colonization that is influenced by soil P supply intensity and space availability. However, how soil P manipulates the root morphological characteristics and AM colonization to compensate for the limitation of root-growth space induced by high-planting density is not clear. Therefore, pot experiments were conducted to investigate interactions between the root growth and AM fungi by optimizing soil P supply to compensate for limited root growth space induced by high-planting density. Similar shoot biomass and P uptake values were obtained in P200 (200 mg P kg-1 soil) under D = 40 (i.e., diameter of the pot is 40 cm) and P400 under D = 30, and similar values were obtained for root length, tap root length, root angle, lateral root density, and AM colonization. However, the improvement in P supply in the root zone, shoot biomass, and P uptake in P400 under D = 20 were lower than in P200 under D = 30, and there were no significant differences in the root parameters between P200 and P400 under D = 20; similarly, the root growth and AM colonization exhibited similar trends. These results suggest that optimizing P supply in the root zone to regulate the interaction between root morphological traits and AM colonization can compensate for limited root-growth space. Although P supply in the root zone increased after the root-growth space was compressed, it could not meet the P demand of maize; thus, to achieve the most efficient use of P under intensive high-density maize production, it is necessary to optimally coordinate root growth space and P supply in the root zone.

Total and denitrifying bacterial communities associated with the interception of nitrate leaching by carbon amendment in the subsoil.

Nitrate leaching is severe in greenhouse where excessive nitrogen is often applied to maintain high crop productivities. In this study, we investigated the effects of carbon amendment in the subsoil on nitrate leaching and the emission of greenhouse gases (CH4 and N2O) using a soil column experiment. Carbon amendment resulted in over 39% reduction in nitrate leaching and 25.3% to 60.6% increase of total N content in the subsoil zone as compared to non-amended control. Strikingly, the abundance of nirS, nosZ, and 16S rRNA were higher in the treatment than the corresponding controls while no significant effect was detected for nirK. Carbon amendment explained 14%, 10%, and 4% of the variation in the community of nosZ, nirS, and nirK, respectively. It also considerably (more than 7 times) enriched genera such as Anaerovorax, Pseudobacteroides, Magnetospirillum, Prolixibacter, Sporobacter, Ignavibacterium, Syntrophobacter, Oxobacter, Hydrogenispora, Desulfosporomusa, Mangrovibacterium, and Sporomusa, as revealed by the analysis of 16S rRNA amplicon. Network analysis further uncovered that carbon amendment enriched three microbial hubs which mainly consists of positively correlated nirS, nosZ, and anaerobic bacterial populations. In summary, carbon amendment in the subsoil mitigated nitrate leaching and increased the nitrogen pool by possible activation of denitrifying and anaerobic bacterial populations. KEY POINTS: • Carbon amendment in subsoil reduced NO3- leaching by over 39% under high N input. • Carbon amendment increased the total N in subsoil from 25.3% to 60.6%. • Carbon amendment enriched nirS- and nosZ-type denitrifying bacteria in subsoil.

Low-intensity ultrasound suppresses low-Mg2+-induced epileptiform discharges in juvenile mouse hippocampal slices.

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.

The role of the substantia nigra pars reticulata anterior in amygdala-kindled seizures.

BACKGROUND: It has been reported that the substantia nigra pars reticulata (SNr) is of regional differences and involved in the initiation, generalization, and cessation of seizures. However, neuropharmacological investigations into the role of the SNr anterior (SNra) in temporal lobe epilepsy (TLE) have been inconsistent, suggesting that electrophysiological investigations are needed to elucidate the role of the SNra in TLE. METHODS: Local field potentials (LFPs) and single-unit activities were simultaneously obtained from the basolateral amygdala (BLA) and the SNra in amygdala-kindled mice. The electrophysiological characteristics of the neuronal activities in the BLA and SNra were investigated. Directionality index was used to measure information flow between LFPs in the two areas during kindled seizures. The effects of electrical lesion of the SNra on the kindled seizures were analyzed in fully-kindled mice. RESULTS: The information flow was predominantly from the SNra to the BLA during the clonic-like periods of stage 5 seizures, but this phenomenon was not found during other kindled seizures. In fully-kindled mice, SNra lesions facilitated the kindled seizures. After lesions were inflicted, the afterdischarge durations and clonic-like periods of stage 5 seizures increased significantly. CONCLUSION: The electrophysiological and lesion results show that the SNra may play an anti-convulsant role in amygdala-kindled seizures.

GABAA Receptor Activity Suppresses the Transition from Inter-ictal to Ictal Epileptiform Discharges in Juvenile Mouse Hippocampus.

Exploring the transition from inter-ictal to ictal epileptiform discharges (IDs) and how GABAA receptor-mediated action affects the onset of IDs will enrich our understanding of epileptogenesis and epilepsy treatment. We used Mg2+-free artificial cerebrospinal fluid (ACSF) to induce epileptiform discharges in juvenile mouse hippocampal slices and used a micro-electrode array to record the discharges. After the slices were exposed to Mg2+-free ACSF for 10 min-20 min, synchronous recurrent seizure-like events were recorded across the slices, and each event evolved from inter-ictal epileptiform discharges (IIDs) to pre-ictal epileptiform discharges (PIDs), and then to IDs. During the transition from IIDs to PIDs, the duration of discharges increased and the inter-discharge interval decreased. After adding 3 µmol/L of the GABAA receptor agonist muscimol, PIDs and IDs disappeared, and IIDs remained. Further, the application of 10 µmol/L muscimol abolished all the epileptiform discharges. When the GABAA receptor antagonist bicuculline was applied at 10 µmol/L, IIDs and PIDs disappeared, and IDs remained at decreased intervals. These results indicated that there are dynamic changes in the hippocampal network preceding the onset of IDs, and GABAA receptor activity suppresses the transition from IIDs to IDs in juvenile mouse hippocampus.

Different functional susceptibilities of mouse retinal ganglion cell subtypes to optic nerve crush injury.

In optic neuropathies, the progressive deterioration of retinal ganglion cell (RGC) function leads to irreversible vision loss. Increasing experimental evidence suggests differing susceptibility for RGC functional subtypes. Here with multi-electrode array recordings, RGC functional loss was characterized at multiple time points in a mouse model of optic nerve crush. Firing rate, latency of response and receptive field size were analyzed for ON, OFF and ON-OFF RGCs separately. It was observed that responses and receptive fields of OFF cells were impaired earlier than ON cells after the injury. For the ON-OFF cells, the OFF component of response was also more susceptible to optic nerve injury than the ON component. Moreover, more ON transient cells survived than ON sustained cells post the crush, implying a diversified vulnerability for ON cells. Together, these data support the contention that RGCs' functional degeneration in optic nerve injury is subtype dependent, a fact that needs to be considered when developing treatments of glaucomatous retinal ganglion cell degeneration and other optic neuropathies.

The Subiculum: A Potential Site of Ictogenesis in a Neonatal Seizure Model.

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 (HP) 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 HP. Bumetanide efficiently blocked seizures in the neonatal HP, 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 HP. Furthermore, Western blotting analysis showed that NKCC1 expression was lower in the subiculum than that in the HP, whereas the expression of NMDAR subunits, NR2A and NR2B, was higher in the subiculum than that in the HP. Our results revealed that the subiculum was a potential site of ictogenesis in neonatal seizures and possessed similar seizure susceptibility to the HP. GABAergic excitation resulting from NKCC1 may play a less dominant role during ictogenesis in the subiculum than that in the HP. The subicular ictogenesis may be related to the glutamatergic excitation mediated by NMDARs.

Interaction between Thalamus and Hippocampus in Termination of Amygdala-Kindled Seizures in Mice.

The thalamus and hippocampus have been found both involved in the initiation, propagation, and termination of temporal lobe epilepsy. However, the interaction of these regions during seizures is not clear. The present study is to explore whether some regular patterns exist in their interaction during the termination of seizures. Multichannel in vivo recording techniques were used to record the neural activities from the cornu ammonis 1 (CA1) of hippocampus and mediodorsal thalamus (MDT) in mice. The mice were kindled by electrically stimulating basolateral amygdala neurons, and Racine's rank standard was employed to classify the stage of behavioral responses (stage 1~5). The coupling index and directionality index were used to investigate the synchronization and information flow direction between CA1 and MDT. Two main results were found in this study. (1) High levels of synchronization between the thalamus and hippocampus were observed before the termination of seizures at stage 4~5 but after the termination of seizures at stage 1~2. (2) In the end of seizures at stage 4~5, the information tended to flow from MDT to CA1. Those results indicate that the synchronization and information flow direction between the thalamus and the hippocampus may participate in the termination of seizures.

The oscillation-like activity in bullfrog ON-OFF retinal ganglion cell.

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.

Coding Properties of Mouse Retinal Ganglion Cells with Dual-Peak Patterns with Respect to Stimulus Intervals.

How visual information is encoded in spikes of retinal ganglion cells (RGCs) is essential in visual neuroscience. In the present study, we investigated the coding properties of mouse RGCs with dual-peak patterns with respect to visual stimulus intervals. We first analyzed the response properties, and observed that the latencies and spike counts of the two response peaks in the dual-peak pattern exhibited systematic changes with the preceding light-OFF interval. We then applied linear discriminant analysis (LDA) to assess the relative contributions of response characteristics of both peaks in information coding regarding the preceding stimulus interval. It was found that for each peak, the discrimination results were far better than chance level based on either latency or spike count, and were further improved by using the combination of the two parameters. Furthermore, the best discrimination results were obtained when latencies and spike counts of both peaks were considered in combination. In addition, the correct rate for stimulation discrimination was higher when RGC population activity was considered as compare to single neuron's activity, and the correct rate was increased with the group size. These results suggest that rate coding, temporal coding, and population coding are all involved in encoding the different stimulus-interval patterns, and the two response peaks in the dual-peak pattern carry complementary information about stimulus interval.

[Information coding in retinal ganglion cells].

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.

Temporal properties of dual-peak responses of mouse retinal ganglion cells and effects of inhibitory pathways.

Dual-peak responses of retinal ganglion cells (RGCs) are observed in various species, previous researches suggested that both response peaks were involved in retinal information coding. In the present study, we investigated the temporal properties of the dual-peak responses recorded in mouse RGCs elicited by spatially homogeneous light flashes and the effect of the inhibitory inputs mediated by GABAergic and/or glycinergic pathways. We found that the two peaks in the dual-peak responses exhibited distinct temporal dynamics, similar to that of short-latency and long-latency single-peak responses respectively. Pharmacological studies demonstrated that the application of exogenous GABA or glycine greatly suppressed or even eliminated the second peak of the cells' firing activities, while little change was induced in the first peak. Co-application of glycine and GABA led to complete elimination of the second peak. Moreover, application of picrotoxin or strychnine induced dual-peak responses in some cells with transient responses by unmasking a second response phase. These results suggest that both GABAergic and glycinergic pathways are involved in the dual-peak responses of the mouse RGCs, and the two response peaks may arise from distinct pathways that would converge on the ganglion cells.

The Spatiotemporal Dynamics of Phase Synchronization during Epileptogenesis in Amygdala-Kindling Mice.

The synchronization among the activities of neural populations in functional regions is one of the most important electrophysiological phenomena in epileptic brains. The spatiotemporal dynamics of phase synchronization was investigated to reveal the reciprocal interaction between different functional regions during epileptogenesis. Local field potentials (LFPs) were recorded simultaneously from the basolateral amygdala (BLA), the cornu ammonis 1 of hippocampus (CA1) and the mediodorsal nucleus of thalamus (MDT) in the mouse amygdala-kindling models during the development of epileptic seizures. The synchronization of LFPs was quantified between BLA, CA1 and MDT using phase-locking value (PLV). During amygdala kindling, behavioral changes (from stage 0 to stage 5) of mice were accompanied by after-discharges (ADs) of similar waveforms appearing almost simultaneously in CA1, MDT, as well as BLA. AD durations were positively related to the intensity of seizures. During seizures at stages 1~2, PLVs remained relatively low and increased dramatically shortly after the termination of the seizures; by contrast, for stages 3~5, PLVs remained a relatively low level during the initial period but increased dramatically before the seizure termination. And in the theta band, the degree of PLV enhancement was positively associated with seizure intensity. The results suggested that during epileptogenesis, the functional regions were kept desynchronized rather than hyper-synchronized during either the initial or the entire period of the seizures; so different dynamic patterns of phase synchronization may be involved in different periods of the epileptogenesis, and this might also reflect that during seizures at different stages, the mechanisms underlying the dynamics of phase synchronization were different.