Premature Deaths in Brazil Associated With Long-Term Exposure to PM2.5 From Amazon Fires Between 2016 and 2019.

Amazonian deforestation from slash-and-burn practices is a significant contributor to biomass burning within Brazil. Fires emit carbonaceous aerosols that negatively impact human health by increasing fine particulate matter (PM2.5) exposure. These negative effects on health compound the already detrimental climatological and ecological impacts. Despite high biomass burning emissions in Brazil and the international attention drawn by the relaxation of Amazon protections in 2019, little is known about the health impacts from PM2.5 exposure attributable to these fires. We estimate PM2.5-related premature deaths in Brazil associated with biomass burning, focusing on temporal, interannual, and spatial trends. We find that during the fire season of 2019, 4,966 (2,427, 8,340) premature deaths were attributable to fire emissions making up 10% (5, 17) of all PM2.5-related premature deaths in Brazil. Between the 2019 and 2018 seasons, fire emissions increased by 1.37 Tg (1.00, 2.18) or 115% (60, 201), which was responsible for an increase in health impacts of 2,109 (965, 3,623) premature deaths or 74% (54, 98). Biomass burning emissions throughout Brazil contribute significantly to premature deaths, with the largest burning events occurring in northwestern Brazil. The impact of fires on PM2.5-related premature deaths is highest in heavily populated regions despite their fires being 1 to 2 orders of magnitude smaller than the largest burning events. Results from this study characterize the extent to which elevated PM2.5 exposure levels owing to fires affect public health in Brazil and present an additional, public health-focused, support for increased Amazon protections.

Quantifying global terrestrial methanol emissions using observations from the TES satellite sensor.

We employ new global space-based measurements of atmospheric methanol from the Tropospheric Emission Spectrometer (TES) with the adjoint of the GEOS-Chem chemical transport model to quantify terrestrial emissions of methanol to the atmosphere. Biogenic methanol emissions in the model are based on version 2.1 of the Model of Emissions of Gases and Aerosols from Nature (MEGANv2.1), using leaf area data from NASA's Moderate Resolution Imaging Spectroradiometer (MODIS) and GEOS-5 assimilated meteorological fields. We first carry out a pseudo observation test to validate the overall approach, and find that the TES sampling density is sufficient to accurately quantify regional- to continental-scale methanol emissions using this method. A global inversion of two years of TES data yields an optimized annual global surface flux of 122 Tg yr-1 (including biogenic, pyrogenic, and anthropogenic sources), an increase of 60 % from the a priori global flux of 76 Tg yr-1. Global terrestrial methanol emissions are thus nearly 25 % those of isoprene (~540 Tg yr-1), and are comparable to the combined emissions of all anthropogenic volatile organic compounds (~100-200 Tg yr-1). Our a posteriori terrestrial methanol source leads to a strong improvement of the simulation relative to an ensemble of airborne observations, and corroborates two other recent top-down estimates (114-120 Tg yr-1) derived using in situ and space-based measurements. Inversions testing the sensitivity of optimized fluxes to model errors in OH, dry deposition, and oceanic uptake of methanol, as well as to the assumed a priori constraint, lead to global fluxes ranging from 118 to 126 Tg yr-1. The TES data imply a relatively modest revision of model emissions over most of the tropics, but a significant upward revision in midlatitudes, particularly over Europe and North America. We interpret the inversion results in terms of specific source types using the methanol : CO correlations measured by TES, and find that biogenic emissions are overestimated relative to biomass burning and anthropogenic emissions in central Africa and southeastern China, while they are underestimated in regions such as Brazil and the US. Based on our optimized emissions, methanol accounts for > 25 % of the photochemical source of CO and HCHO over many parts of the northern extratropics during springtime, and contributes ~6 % of the global secondary source of those compounds annually.

[Value of hyperbaric oxygen in the treatment of advanced skull base osteomyelitis]. / Nutzen der HBO bei der Therapie der fortgeschrittenen Schädelbasisosteomyelitis.

BACKGROUND: The therapy of skull base osteomyelitis (SBO) is still challenging. Standard therapy includes the use of antibiotics, local treatment and surgical removal of necrotic bone and tissue. This study reports on the value of adjuvant hyperbaric oxygen therapy with respect to the functional outcome in SBO. Furthermore diagnostic signs especially on imaging are elaborated. METHODS: The retrospective study included all cases of SBO treated between July 2002 and November 2006 in our department. Clinical data, microbiology, laboratory and radiological findings were reviewed. Treatment modality data, especially the use of adjuvant hyperbaric oxygen therapy (HBO) were analysed. The outcome with regard to neurological or functional deficit was assessed and the value of adjuvant HBO therapy was evaluated in comparison with the literature. RESULTS: In the given time period ten patients with SBO could be selected. The presumption diagnosis based on CT and/or MRI in first line. It was confirmed by histology in all cases. Treatment included high dose antibiotics, surgical debridement and adjuvant HBO therapy. Cure rate of treated patients was 8/8, regarding inflammatory signs. Two patients refused any further therapy during the course, in both the outcome was fatal. Functional recovery of cranial nerve deficits could be reached in 6/8. Two patients had residual cranial nerve palsies. The outcome was mainly influenced by the treatment modality and duration of cranial nerve involvement. CONCLUSIONS: Adjuvant hyperbaric oxygen therapy has been proved to be highly effective in the treatment of advanced SBO. Cranial nerve palsies can recover completely under optimized treatment including adjuvant HBO therapy.

Local and systemic hemorheological effects of cerebral hyper- and hypoperfusion in a porcine model.

Using a well defined pig model, we investigated whether cerebral hypertension and hypotension influence hemorheological factors. After surgical preparation and stabilization, periods of hyperventilation, controlled periods of cerebral perfusion pressure increases and decreases were utilized. After each period, blood samples were collected from the cannulated femoral artery and vein, and from the superior sagittal sinus. Erythrocyte deformability, whole blood and plasma viscosity and hematological parameters were determined. Erythrocyte deformability significantly worsened in arterial samples after hypertension and hypotension, and in sinus samples it was impaired after hypotension period. Hematocrit significantly increased in arterial and sinus samples during hypertensive period, accompanied by similar alterations in whole blood viscosity. We conclude that hemodynamic changes caused by hyperventilation, hyper- or hypotension can influence hemorheological factors, and suggest that the rheological alterations can affect local hemodynamic and metabolic conditions.

Quantitative measures of cluster quality for use in extracellular recordings.

While the use of multi-channel electrodes (stereotrodes and tetrodes) has allowed for the simultaneous recording and identification of many neurons, quantitative measures of the quality of neurons in such recordings are lacking. In multi-channel recordings, each spike waveform is discriminated in a high-dimensional space, making traditional measures of unit quality inapplicable. We describe two measures of unit isolation quality, Lratio and Isolation Distance, and evaluate their performance using simulations and tetrode recordings. Both measures quantified how well separated the spikes of one cluster (putative neuron) were from other spikes recorded simultaneously on the same multi-channel electrode. In simulations and tetrode recordings, both Lratio and Isolation Distance discriminated well- and poorly-separated clusters. In data sets from the rodent hippocampus in which neurons were simultaneously recorded intracellularly and extracellularly, values of Isolation Distance and Lratio were related to the correct identification of spikes.

Brain tissue oxygen monitoring for assessment of autoregulation: preliminary results suggest a new hypothesis.

Brain tissue oxygen monitoring (P(ti)O2 (Neurotrend, Codman, Germany) was employed in addition to standard intracranial pressure (ICP) and cerebral perfusion pressure (CPP) monitoring in seven patients with severe neuronal damage of heterogeneous etiology. The correlation between P(ti)O2 changes and CPP fluctuations during periods of 30 minutes were analyzed, when CPP was above 70 mmHg and lower than 100 mmHg. A new ratio, the CPP-oxygen-reactivity (COR) index was calculated as COR=delta p(ti)O2 %/delta CPP%. The patient COR values were compared to those found in the brain of six noninjured anesthetized piglets. The analysis was performed to determine the significance of synchronous fluctuations of CPP and P(ti)O2, when CPP is above the lower threshold of autoregulation. The correlation between CPP variations and p(ti)O2 variations was found to be strong (R(mean)) = 0.74 +/- 0.17) in the patients and was weak in the uninjured animals (R(mean)) =0.38 +/- 0.43). The COR (mean) was 2.05 +/- 0.57 in patients and 0.78 +/- 0.6 in the animals. In the injured brain of our patients, we observed an unexpectedly close correlation between P(ti)O2 and CPP variations when CPP levels were within a therapeutically targeted range (70 to 100 mmHg). In a porcine model, we could not find this relationship in the noninjured brain. We speculate that an increased COR might be indicative for an impaired local pressure autoregulation. The preliminary data suggest that COR values above "1" might be pathologic. However, the reported sample sizes are too small to provide sufficient statistical power to justify inferential statistical analyses. As such, results are presented with descriptive statistics only, and should be regarded as a hypothesis.

Dopamine modulation of neuronal function in the monkey prefrontal cortex.

We developed a brain slice preparation that allowed us to apply whole-cell recordings to examine the electrophysiological properties of identified synapses, neurons, and local circuits in the dorsolateral prefrontal cortex (DLPFC) of macaque monkeys. In this article, we summarize the results from some of our recent and current in vitro studies in the DLPFC with special emphasis on the modulatory effects of dopamine (DA) receptor activation on pyramidal and nonpyramidal cell function in superficial layers in DLPFC areas 46 and 9.

Temporal interaction between single spikes and complex spike bursts in hippocampal pyramidal cells.

Cortical pyramidal cells fire single spikes and complex spike bursts. However, neither the conditions necessary for triggering complex spikes, nor their computational function are well understood. CA1 pyramidal cell burst activity was examined in behaving rats. The fraction of bursts was not reliably higher in place field centers, but rather in places where discharge frequency was 6-7 Hz. Burst probability was lower and bursts were shorter after recent spiking activity than after prolonged periods of silence (100 ms-1 s). Burst initiation probability and burst length were correlated with extracellular spike amplitude and with intracellular action potential rising slope. We suggest that bursts may function as "conditional synchrony detectors," signaling strong afferent synchrony after neuronal silence, and that single spikes triggered by a weak input may suppress bursts evoked by a subsequent strong input.

Revisiting the role of the hippocampal mossy fiber synapse.

The mossy fiber pathway has long been considered to provide the major source of excitatory input to pyramidal cells of hippocampal area CA3. In this review we describe anatomical and physiological properties of this pathway that challenge this view. We argue that the mossy fiber pathway does not provide the main input to CA3 pyramidal cells, and that the short-term plasticity and amplitude variance of mossy fiber synapses may be more important features than their long-term plasticity or absolute input strength.

Action potential threshold of hippocampal pyramidal cells in vivo is increased by recent spiking activity.

Understanding the mechanisms that influence the initiation of action potentials in single neurons is an important step in determining the way information is processed by neural networks. Therefore, we have investigated the properties of action potential thresholds for hippocampal neurons using in vivo intracellular recording methods in Sprague-Dawley rats. The use of in vivo recording has the advantage of the presence of naturally occurring spatio-temporal patterns of synaptic activity which lead to action potential initiation. We have found there is a large variability in the threshold voltage (5.7+/-1.7 mV; n=22) of individual action potentials. We have identified two separate factors that contribute to this variation in threshold: (1) fast rates of membrane potential change prior to the action potential are associated with more hyperpolarized thresholds (increased excitability) and (2) the occurrence of other action potentials in the 1 s prior to any given action potential is associated with more depolarized thresholds (decreased excitability). We suggest that prior action potentials cause sodium channel inactivation that recovers with approximately a 1-s time constant and thus depresses action potential threshold during this period.

Experiences with continuous intra-arterial blood gas monitoring.

Management of critically ill patients requires frequent arterial blood gas analyses for assessing the pulmonary situation and adjusting ventilator settings and circulatory therapeutic measures. Continuous arterial blood gas analysis is a real-time monitoring tool, which reliably detects the onset of adverse pulmonary effects. It gives rapid confirmation of ventilator setting changes and resuscitation and helps to ensure precise adjustment of therapy. In this study a newly available fiber optic sensor system has been employed for continuous intraarterial blood gas monitoring. The measurement performance was compared with a bench top blood gas analyzer. A prospective study was performed enrolling 20 patients undergoing surgery. A comparison between intermittent blood gas analyses (ABL Radiometer 610) and the results of continuous blood gas monitoring (Paratrend 7+, Agilent Technol.) was performed by simultaneous measurements. Statistical analysis in agreement with the method of "Bland and Altman" was employed. Two case reports are provided of patients with Acute Adult Respiratory Distress Syndrome and rapid changes in ventilator settings. Over a range of arterial oxygenation from 10 to 50 kPa the bias for pO2-measurement was 0.2 (limits of agreement 4), R2 = 0.9. If the arterial pO2 was higher than 50 kPa the bias was -7 (10) kPa. PCO2-measurement showed a bias of 0.25 (limits of agreement 0.45), R2 = 0.7. pH bias was -0.02 (limits of agreement 0.04), R2 = 0.7. The Paratrend 7+ sensor proved to be clinical feasible and showed an improved precision in terms of clinical situations with an arterial pO2 smaller than 50 kPa. However, the results are not much different regarding the findings with older systems consisting of hybrid technology combining optodes and electrochemical oxygen measurement. The advantages might be seen if the sensor is used for a period over several days in patients on ICU as demonstrated by the two case reports.

The apical shaft of CA1 pyramidal cells is under GABAergic interneuronal control.

Dendrites of pyramidal cells perform complex amplification and integration (reviewed in Refs 5, 9, 12 and 20). The presence of a large proximal apical dendrite has been shown to have functional implications for neuronal firing patterns (13) and under a variety of experimental conditions, the largest increases in intracellular Ca2+ occur in the apical shaft.(4,8,15,16,19,21-23) An important step in understanding the functional role of the proximal apical dendrite is to describe the nature of synaptic input to this dendritic region. Using light and electron microscopic methods combined with in vivo labeling of rat hippocampal CA1 pyramidal cells, we examined the total number of GABAergic and non-GABAergic inputs converging onto the first 200microm of the apical trunk. The number of spines associated with excitatory terminals increased from <0.2 spines/microm adjacent to the soma to 5.5 spines/microm at 200microm from the soma, whereas the number of GABAergic, symmetric terminals decreased from 0.8/microm to 0.08/microm over the same anatomical region. GABAergic terminals were either parvalbumin-, cholecystokinin- or vasointestinal peptide-immunoreactive. These findings indicate that the apical dendritic trunk mainly receives synaptic input from GABAergic interneurons. GABAergic inhibition during network oscillation may serve to periodically isolate the dendritic compartments from the perisomatic action potential generating sites.

Dopamine increases excitability of pyramidal neurons in primate prefrontal cortex.

Dopaminergic modulation of neuronal networks in the dorsolateral prefrontal cortex (PFC) is believed to play an important role in information processing during working memory tasks in both humans and nonhuman primates. To understand the basic cellular mechanisms that underlie these actions of dopamine (DA), we have investigated the influence of DA on the cellular properties of layer 3 pyramidal cells in area 46 of the macaque monkey PFC. Intracellular voltage recordings were obtained with sharp and whole cell patch-clamp electrodes in a PFC brain-slice preparation. All of the recorded neurons in layer 3 (n = 86) exhibited regular spiking firing properties consistent with those of pyramidal neurons. We found that DA had no significant effects on resting membrane potential or input resistance of these cells. However DA, at concentrations as low as 0.5 microM, increased the excitability of PFC cells in response to depolarizing current steps injected at the soma. Enhanced excitability was associated with a hyperpolarizing shift in action potential threshold and a decreased first interspike interval. These effects required activation of D1-like but not D2-like receptors since they were inhibited by the D1 receptor antagonist SCH23390 (3 microM) but not significantly altered by the D2 antagonist sulpiride (2.5 microM). These results show, for the first time, that DA modulates the activity of layer 3 pyramidal neurons in area 46 of monkey dorsolateral PFC in vitro. Furthermore the results suggest that, by means of these effects alone, DA modulation would generally enhance the response of PFC pyramidal neurons to excitatory currents that reach the action potential initiation site.

Intracellular features predicted by extracellular recordings in the hippocampus in vivo.

Multichannel tetrode array recording in awake behaving animals provides a powerful method to record the activity of large numbers of neurons. The power of this method could be extended if further information concerning the intracellular state of the neurons could be extracted from the extracellularly recorded signals. Toward this end, we have simultaneously recorded intracellular and extracellular signals from hippocampal CA1 pyramidal cells and interneurons in the anesthetized rat. We found that several intracellular parameters can be deduced from extracellular spike waveforms. The width of the intracellular action potential is defined precisely by distinct points on the extracellular spike. Amplitude changes of the intracellular action potential are reflected by changes in the amplitude of the initial negative phase of the extracellular spike, and these amplitude changes are dependent on the state of the network. In addition, intracellular recordings from dendrites with simultaneous extracellular recordings from the soma indicate that, on average, action potentials are initiated in the perisomatic region and propagate to the dendrites at 1.68 m/s. Finally we determined that a tetrode in hippocampal area CA1 theoretically should be able to record electrical signals from approximately 1, 000 neurons. Of these, 60-100 neurons should generate spikes of sufficient amplitude to be detectable from the noise and to allow for their separation using current spatial clustering methods. This theoretical maximum is in contrast to the approximately six units that are usually detected per tetrode. From this, we conclude that a large percentage of hippocampal CA1 pyramidal cells are silent in any given behavioral condition.

Accuracy of tetrode spike separation as determined by simultaneous intracellular and extracellular measurements.

Simultaneous recording from large numbers of neurons is a prerequisite for understanding their cooperative behavior. Various recording techniques and spike separation methods are being used toward this goal. However, the error rates involved in spike separation have not yet been quantified. We studied the separation reliability of "tetrode" (4-wire electrode)-recorded spikes by monitoring simultaneously from the same cell intracellularly with a glass pipette and extracellularly with a tetrode. With manual spike sorting, we found a trade-off between Type I and Type II errors, with errors typically ranging from 0 to 30% depending on the amplitude and firing pattern of the cell, the similarity of the waveshapes of neighboring neurons, and the experience of the operator. Performance using only a single wire was markedly lower, indicating the advantages of multiple-site monitoring techniques over single-wire recordings. For tetrode recordings, error rates were increased by burst activity and during periods of cellular synchrony. The lowest possible separation error rates were estimated by a search for the best ellipsoidal cluster shape. Human operator performance was significantly below the estimated optimum. Investigation of error distributions indicated that suboptimal performance was caused by inability of the operators to mark cluster boundaries accurately in a high-dimensional feature space. We therefore hypothesized that automatic spike-sorting algorithms have the potential to significantly lower error rates. Implementation of a semi-automatic classification system confirms this suggestion, reducing errors close to the estimated optimum, in the range 0-8%.

The multifarious hippocampal mossy fiber pathway: a review.

The hippocampal mossy fiber pathway between the granule cells of the dentate gyrus and the pyramidal cells of area CA3 has been the target of numerous scientific studies. Initially, attention was focused on the mossy fiber to CA3 pyramidal cell synapse because it was suggested to be a model synapse for studying the basic properties of synaptic transmission in the CNS. However, the accumulated body of research suggests that the mossy fiber synapse is rather unique in that it has many distinct features not usually observed in cortical synapses. In this review, we have attempted to summarize the many unique features of this hippocampal pathway. We also have attempted to reconcile some discrepancies that exist in the literature concerning the pharmacology, physiology and plasticity of this pathway. In addition we also point out some of the experimental challenges that make electrophysiological study of this pathway so difficult.Finally, we suggest that understanding the functional role of the hippocampal mossy fiber pathway may lie in an appreciation of its variety of unique properties that make it a strong yet broadly modulated synaptic input to postsynaptic targets in the hilus of the dentate gyrus and area CA3 of the hippocampal formation.

[Continuous recording of cardiac output volume with the OptiQ system--experiences with clinical application]. / Kontinuierliche Messung des Herzzeitvolumens mit dem OptiQ-System--Erfahrungen im klinischen Einsatz.

This report discusses initial experiences with the clinical application of continuous cardiac output measurement (OptiQ SvO2/CCO-System). The system was used in 9 intensive care patients suffering either global cardiac insufficiency or systemic inflammatory response syndrome. Continuous cardiac output measurement was recorded during a period of stable blood pressure conditions and compared with the results of the conventional thermodilution method (bolus technique) in these patients. Regression analyses yielded r = 0.523 (r2 = 0.274) for the "urgent" mode, r = 0.943 (r2 = 0.889) for the "fast" mode, r = 0.953 (r2 = 0.907) for the "fast filter" mode and r = 0.990 (r2 = 0.980) for the "normal" mode. Mean differences between the continuous and the bolus technique were calculated as -0.13 +/- 1.81 l/min for the "urgent" mode, -0.42 +/- 0.51 l/min for the "fast" mode, -0.14 +/- 0.48 l/min for the "fast filter" mode and -0.08 +/- 0.19 l/min for the "normal" mode. After a period of two days, the costs of the conventional bolus technique significantly exceeded those of continuous measurement. The expenses for the conventional thermodilution technique are largely determined by the frequency of application and, hence, by the personnel and laboratory costs. In our experience, easy component handling and stable measuring properties make this new method of continuous cardiac output monitoring a valuable method in the diagnose and care of patients who are critically ill.

[Cerebral oxygen reactivity determination--a simple test with potential prognostic relevance]. / Zerebrale Sauerstoffreaktivitätsbestimmung--ein einfacher Test mit potentiell prognostischer Relevanz.

UNLABELLED: Brain tissue oximetry (ptiO2) using flexible micro-polarographic electrodes is a loco-regional approach to monitor oxygen supply to the injured brain, after neuronal damage. In patients after severe head injury (SHI), disturbances of CBF and CO2 related vasoconstriction have been demonstrated. CO2 reactivity testing may assist to determine outcome in these patients. Not much information is available on the preservation of vasoreactivity to arterial hyperoxia after neuronal damage. Therefore, we studied the response of ptiO2 in 7 piglets and in 14 patients on day one after trauma to 100% FiO2 ventilation (O2rea) and analyzed the 3 month outcome using the Glasgow-Outcome-Score (GOS). In the animal study, we placed a Paratrend 7 (P7) sensor for ptiO2 measurements in the non injured frontal white matter. The animals were anesthetized and mechanically ventilated. FiO2 was increased from 30 (+/- 5)% to 100% over a period of 5 minutes. In patients, we placed the P7 probe in the frontal lobe. FiO2 was increased from 35 (+/- 5)% to 100% over a period of 6 hours. O2rea was tested by calculating the percentage change of ptiO2 during 100% FiO2 ventilation, compared to the baseline value of 35% FiO2. By analyzing the patient outcome, we were able to define two patient populations according to the GOS at three month (Group I: favorable outcome [GOS 0-2]; Group II: poor outcome [GOS 3-4]). For the non-injured brain tissue in animals were revealed an O2rea = 0.21 (+/- 0.12). PATIENTS: Group I: O2rea = 0.4 (+/- 0.16); Group II: 0.9 (+/- 0.6). Group I and II were statistical significant different (p < 0.05; unpaired t-test). Oxygen reactivity in severely head patients is a simple test with prognostic value using ptiO2 measurement. These results may be explained by the close relationship of CBF disturbances to oxygen vasoreactivity after traumatic brain injury. The O2rea in animals without neuronal damage is smaller than in patients after SHI. We speculate, the animal data could be considered as normal value of O2rea in non injured brain tissue.

Ultra-slow oscillation (0.025 Hz) triggers hippocampal afterdischarges in Wistar rats.

Oscillations in neuronal networks are assumed to serve various physiological functions, from coordination of motor patterns to perceptual binding of sensory information. Here, we describe an ultra-slow oscillation (0.025 Hz) in the hippocampus. Extracellular and intracellular activity was recorded from the CA1 and subicular regions in rats of the Wistar and Sprague-Dawley strains, anesthetized with urethane. In a subgroup of Wistar rats (23%), spontaneous afterdischarges (4.7+/-1.6 s) occurred regularly at 40.8+/-15.7 s. The afterdischarge was initiated by a fast increase of population synchrony (100-250 Hz oscillation; "tonic" phase), followed by large-amplitude rhythmic waves and associated action potentials at gamma and beta frequency (15-50 Hz; "clonic" phase). The afterdischarges were bilaterally synchronous and terminated relatively abruptly without post-ictal depression. Single-pulse stimulation of the commissural input could trigger afterdischarges, but only at times when they were about to occur. Commissural stimulation evoked inhibitory postsynaptic potentials in pyramidal cells. However, when the stimulus triggered an afterdischarge, the inhibitory postsynaptic potential was absent and the cells remained depolarized during most of the afterdischarge. Afterdischarges were not observed in the Sprague-Dawley rats. Long-term analysis of interneuronal activity in intact, drug-free rats also revealed periodic excitability changes in the hippocampal network at 0.025 Hz. These findings indicate the presence of an ultra-slow oscillation in the hippocampal formation. The ultra-slow clock induced afterdischarges in susceptible animals. We hypothesize that a transient failure of GABAergic inhibition in a subset of Wistar rats is responsible for the emergence of epileptiform patterns.

Hebbian modification of a hippocampal population pattern in the rat.

1. The study of the physiological role of long-term potentiation (LTP) is often hampered by the challenge of finding a physiological event that can be used to assess synaptic strength. We explored the possibility of utilising a naturally occurring event, the hippocampal sharp wave (SPW), for the assessment of synaptic strength and the induction of LTP in vivo. 2. We used two methods in which hippocampal cells were either recorded intracellularly or extracellularly in vivo. In both cases, a linear association between the magnitude of the SPW and cellular responsiveness was observed. 3. LTP was induced by depolarising cells during SPWs by either direct intracellular current injection or extracellular microstimulation adjacent to the cell body. Both of these approaches led to an increase in the slope of the linear association between SPWs and cellular responsiveness. 4. This change was achieved without a rise in overall cell excitability, implying that the synapses providing input to CA1 cells during sharp waves had undergone potentiation. 5. Our findings show that the Hebbian pairing of cellular activation with spontaneous, naturally occurring synaptic events is capable of inducing LTP.