Learning about brain physiology and complexity from the study of the epilepsies

The brain is a complex system, which produces emergent properties such as those associated with activity-dependent plasticity in processes of learning and memory. Therefore, understanding the integrated structures and functions of the brain is well beyond the scope of either superficial or extremely reductionistic approaches. Although a combination of zoom-in and zoom-out strategies is desirable when the brain is studied, constructing the appropriate interfaces to connect all levels of analysis is one of the most difficult challenges of contemporary neuroscience. Is it possible to build appropriate models of brain function and dysfunctions with computational tools? Among the best-known brain dysfunctions, epilepsies are neurological syndromes that reach a variety of networks, from widespread anatomical brain circuits to local molecular environments. One logical question would be: are those complex brain networks always producing maladaptive emergent properties compatible with epileptogenic substrates? The present review will deal with this question and will try to answer it by illustrating several points from the literature and from our laboratory data, with examples at the behavioral, electrophysiological, cellular and molecular levels. We conclude that, because the brain is a complex system compatible with the production of emergent properties, including plasticity, its functions should be approached using an integrated view. Concepts such as brain networks, graphics theory, neuroinformatics, and e-neuroscience are discussed as new transdisciplinary approaches dealing with the continuous growth of information about brain physiology and its dysfunctions. The epilepsies are discussed as neurobiological models of complex systems displaying maladaptive plasticity.FAPESPFAPESP-CinapceCNPq-ProsulPROEX/CAPES-FisiologiaPROEX/CAPES-NeurologiaFAEP

Evaluation of cardiovascular risk factors in the Wistar Audiogenic Rat (WAR) Strain

Introduction: Risk factors for life-threatening cardiovascular events were evaluated in an experimental model of epilepsy, the Wistar Audiogenic Rat (WAR) strain. Methods: We used long-term ECG recordings in conscious, one year old, WAR and Wistar control counterparts to evaluate spontaneous arrhythmias and heart rate variability, a tool to assess autonomic cardiac control. Ventricular function was also evaluated using the pressure-volume conductance system in anesthetized rats. Results: Basal RR interval (RRi) was similar between WAR and Wistar rats (188\ub15 vs 199\ub16 ms). RRi variability strongly suggests that WAR present an autonomic imbalance with sympathetic overactivity, which is an isolated risk factor for cardiovascular events. Anesthetized WAR showed lower arterial pressure (92\ub13 vs 115\ub15 mmHg) and exhibited indices of systolic dysfunction, such as higher ventricle end-diastolic pressure (9.2\ub10.6 vs 5.6\ub11 mmHg) and volume (137\ub19 vs 68\ub19 \u3bcL) as well as lower rate of increase in ventricular pressure (5266\ub1602 vs 7320\ub1538 mmHg.s-1). Indices of diastolic cardiac function, such as lower rate of decrease in ventricular pressure (-5014\ub1780 vs -7766\ub1998 mmHg.s-1) and a higher slope of the linear relationship between end-diastolic pressure and volume (0.078\ub10.011 vs 0.036\ub10.011 mmHg.\u3bcL), were also found in WAR as compared to Wistar control rats. Moreover, Wistar rats had 3 to 6 ventricular ectopic beats, whereas WAR showed 15 to 30 ectopic beats out of the 20,000 beats analyzed in each rat. Conclusions: The autonomic imbalance observed previously at younger age is also present in aged WAR and, additionally, a cardiac dysfunction was also observed in the rats. These findings make this experimental model of epilepsy a valuable tool to study risk factors for cardiovascular events in epilepsy

Glass pipette-carbon fiber microelectrodes for evoked potential recordings

Current methods for recording field potentials with tungsten electrodes make it virtually impossible to use the same recording electrode also as a lesioning electrode, for example for histological confirmation of the recorded site, because the lesioning procedure usually wears off the tungsten tip. Therefore, the electrode would have to be replaced after each lesioning procedure, which is a very high cost solution to the problem. We present here a low cost, easy to make, high quality glass pipette-carbon fiber microelectrode that shows resistive, signal/noise and electrochemical coupling advantages over tungsten electrodes. Also, currently used carbon fiber microelectrodes often show problems with electrical continuity, especially regarding electrochemical applications using a carbon-powder/resin mixture, with consequent low performance, besides the inconvenience of handling such a mixture. We propose here a new method for manufacturing glass pipette-carbon fiber microelectrodes with several advantages when recording intracerebral field potential

Possible Interaction Between The Inferior Colliculus And The Substantia Nigra In Audiogenic Seizures In Wistar Rats

Male Wistar rats were tested for sensitivity to audiogenic seizures (AS; 110 dB), using an audiogenic severity index (SI). Sensitive (S) animals were subjected to bilateral lesion of the inferior colliculus (IC) and/or the lateral lemniscus (LL). Resistant (R) animals were subjected to bilateral lesions of the IC, unilateral sequential lesions of the substantia nigra reticulata (SN) and/or IC (contralateral to one another), and unilateral thalamic and sham lesions. Bilateral lesions of the IC and LL abolish AS in r rats. Lesion of the SN resulted in more pronounced sensitivity to AS than unilateral lesion of IC, in R rats. When the SN lesion was contralateral to a previous IC lesion, the effect was not only an increase in the SI, but also a reversal of the asymmetry generated by IC lesion. 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Low-cost automatic activity data recording system

We describe a low-cost, high quality device capable of monitoring indirect activity by detecting touch-release events on a conducting surface, i.e., the animal's cage cover. In addition to the detecting sensor itself, the system includes an IBM PC interface for prompt data storage. The hardware/software design, while serving for other purposes, is used to record the circadian activity rhythm pattern of rats with time in an automated computerized fashion using minimal cost computer equipment (IBM PC XT). Once the sensor detects a touch-release action of the rat in the upper portion of the cage, the interface sends a command to the PC which records the time (hours-minutes-seconds) when the activity occurred. As a result, the computer builds up several files (one per detector/sensor) containing a time list of all recorded events. Data can be visualized in terms of actograms, indicating the number of detections per hour, and analyzed by mathematical tools such as Fast Fourier Transform (FFT) or cosinor. In order to demonstrate method validation, an experiment was conducted on 8 Wistar rats under 12/12-h light/dark cycle conditions (lights on at 7:00 a.m.). Results show a biological validation of the method since it detected the presence of circadian activity rhythm patterns in the behavior of the rat