Calmodulin-dependent cyclic nucleotide phosphodiesterase activity is altered by 20 microT magnetostatic fields.

Absorbance measurements at 660 nm of calmodulin (CaM) dependent cyclic nucleotide phosphodiesterase activity under cell free conditions indicate that 30-min exposures to weak magnetostatic field intensities alters this activity, compared to zero magnetic field exposures. This effect depends nonlinearly on the concentration of free calcium, with maximum magnetic interaction apparently occurring at an optimal Ca(2+) concentration corresponding to 50% activation (EC(50)). If one regards Ca(2+)/CaM activation as a switching process, then increasing the magnetic field at Ca(2+) levels in excess of optimal acts to bias this switch towards lower calcium concentrations. A magnetic dependence has been previously reported by others in an homologous system, CaM dependent myosin light chain phosphorylation, implying that there may be an underlying magnetic interaction that involves the initial Ca(2+)/CaM binding process common to both enzymatic pathways. The level of magnetostatic intensity at which this effect is observed ( approximately 20 microT) implies that CaM activation may be functionally sensitive to the geomagnetic field.

Physical mechanisms in neuroelectromagnetic therapies.

Physical parameters that are used to characterize different types of electromagnetic devices used in neurotherapy can include power, frequency, carrier frequency, current, magnetic field intensity, and whether an application is primarily electric or primarily magnetic. Currents can range from tens of microamperes to hundreds of milliamperes, magnetic fields from tens of microtesla to more than one tesla, and frequencies from a few Hz to more than 50 GHz. A division into three device categories is proposed, based on the current applied and the specificity of the therapeutic signal. Two research areas have great potential for new neuroelectromagnetic strategies. Studies of endogenous neural oscillatory states suggest using external fields to reinforce or inhibit such states. Also, various independent groups have reported that weak magnetic fields, in particular ion cyclotron resonance fields, are capable of sharply altering behavior in rats.

Enhanced excitability induced by ionizing radiation in the kindled rat.

Evidence derived from both clinical and experimental investigations has suggested an influence of ionizing radiation on focal epileptogenicity. To better characterize this influence we applied focal ionizing radiation to a kindled epileptic focus in the rat amygdala. The right and left basolateral amygdala and right frontal cortex were implanted with concentric bipolar electrodes. Rats were kindled through a minimum of 10 stage 5 seizures by afterdischarge-threshold electrostimulation of the left amygdala, after which generalized seizure thresholds were determined prior to irradiation. The left amygdala was exposed to single-fraction central-axis doses of either 18 or 25 Gy using a beam-collimated (60)Co source (1.25 MeV). Generalized seizure thresholds were then redetermined at weekly intervals for 10 weeks and at monthly intervals for an additional 3 months. We observed no significant changes in seizure threshold during the postirradiation interval; however, we did observe persistent changes in seizure dynamics manifesting within the first week postirradiation. These consisted of an increased tendency for seizure activity to propagate into brain stem circuits during the primary ictus (i.e., "running fits") and an increased tendency for secondary convulsions to emerge postictally. These effects involving seizure dynamics have not been reported previously and appear to represent a radiation-induced disinhibition of one or more neural circuits. The disparity between these effects and earlier reports of seizure-suppressive effects resulting from analogous radiation exposures is discussed in relation to kindling and status epilepticus-induced pathogenesis within the hippocampus.

New model for the avian magnetic compass.

It is proposed that the avian magnetic compass depends on the angle between the horizontal component B(h) of the geomagnetic field (GMF) and E(r), the radial electric field distribution generated by gamma-oscillations within the optic tectum (TeO). We hypothesize that the orientation of the brain relative to B(h) is perceived as a set of electric field ion cyclotron resonance (ICR) frequencies that are distributed in spatially recognizeable regions within the TeO. For typical GMF intensities, the expected ICR frequencies fall within the 20-50 Hz range of gamma-oscillation frequencies observed during visual stimulation. The model builds on the fact that the superficial lamina of the TeO receive signals from the retina that spatially map the visual field. The ICR frequencies are recruited from the local wide-band gamma-oscillations and are superposed on the tectum for interpretation along with other sensory data. As a first approximation, our analysis is restricted to the medial horizontal plane of the TeO. For the bird to fly in a preferred, previously mapped direction relative to B(h), it hunts for that orientation that positions the frequency maxima at appropriate locations on the TeO. This condition can be maintained even as B(h) varies with geomagnetic latitude during the course of long-distance flights. The magnetovisual coordinate system (straight phi, omega) overlaying the two halves of the tectal surface in a nonsymmetric way may imply an additional orienting function for the TeO over and above that of a simple compass (e.g., homing navigation as distinct from migrational navigation).

Weak ELF magnetic field effects on hippocampal rhythmic slow activity.

Several investigations have revealed that electrical activity within the central nervous system (CNS) can be affected by exposure to weak extremely-low-frequency (ELF) magnetic fields. Many of these studies have implicated CNS structures exhibiting endogenous oscillation and synchrony as optimal sites for field coupling. A particularly well characterized structure in this regard is the rat hippocampus. Under urethane anesthesia, synchronous bursting among hippocampal pyramidal neurons produces a large-amplitude quasi-sinusoidal field potential oscillation, termed "rhythmic slow activity" (RSA) or "theta." Using this in vivo model, we investigated the effect of exposure to an externally applied sinusoidal magnetic field (16.0 Hz; 28.9 microT(rms)) on RSA. During a 60-min exposure interval, the probability of RSA decaying to a less coherent mode of oscillation, termed "large irregular-amplitude activity" (LIA), was increased significantly. Moreover, this instability persisted for up to 90 min postexposure. These results are consistent with the hypothesis that endogenous CNS oscillators are uniquely susceptible to field-mediated perturbation and suggest that the sensitivity of these networks to such fields may be far greater than had previously been assumed. This sensitivity may reflect nonlinearities inherent to these networks which permit amplification of endogenous fields mediating the initiation and propagation of neuronal synchrony.

Weak extremely-low-frequency magnetic field-induced regeneration anomalies in the planarian Dugesia tigrina.

We recently reported that cephalic regeneration in the planarian Dugesia tigrina was significantly delayed in populations exposed continuously to combined parallel DC and AC magnetic fields. This effect was consistent with hypotheses suggesting an underlying resonance phenomenon. We report here, in a parallel series of investigations on the same model system, that the incidence of regeneration anomalies presenting as tumor-like protuberances also increases significantly (P < .001) in association with exposure to weak 60 Hz magnetic fields, with peak intensities ranging between 1.0 and 80.0 microT. These anomalies often culminate in the complete disaggregation of the organism. Similar to regeneration rate effects, the incidence of regeneration anomalies is specifically dependent upon the planaria possessing a fixed orientation with respect to the applied magnetic field vectors. However, unlike the regeneration rate effects, the AC magnetic field alone, in the absence of any measurable DC field, is capable of producing these anomalies. Moreover, the incidence of regeneration anomalies follows a clear dose-response relationship as a function of AC magnetic field intensity, with the threshold for induced electric field intensity estimated at 5 microV/m. The addition of either 51.1 or 78.4 microT DC magnetic fields, applied in parallel combination with the AC field, enhances the appearance of anomalies relative to the 60 Hz AC field alone, but only at certain AC field intensities. Thus, whereas our previous study of regeneration rate effects appeared to involve exclusively resonance interactions, the regeneration anomalies reported here appear to result primarily from Faraday induction coupling. These results together with those reported previously point to two distinct physiological effects produced in regenerating planaria by exposure to weak extremely-low-frequency (ELF) magnetic fields. They further suggest that the planarian, which has recently been identified elsewhere as an excellent system for use in teratogenic investigations involving chemical teratogens, might be used similarly in teratogenic investigations involving ELF magnetic fields.

Weak extremely-low-frequency magnetic fields and regeneration in the planarian Dugesia tigrina.

Extremely-low-frequency (ELF), low-intensity magnetic fields have been shown to influence cell signaling processes in a variety of systems, both in vivo and in vitro. Similar effects have been demonstrated for nervous system development and neurite outgrowth. We report that regeneration in planaria, which incorporates many of these processes, is also affected by ELF magnetic fields. The rate of cephalic regeneration, reflected by the mean regeneration time (MRT), for planaria populations regenerating under continuous exposure to combined DC (78.4 muT) and AC (60.0 Hz at 10.0 muTpeak) magnetic fields applied in parallel was found to be significantly delayed (P << 0.001) by 48 +/- 1 h relative to two different types of control populations (MRT approximately 140 +/- 12 h). One control population was exposed to only the AC component of this field combination, while the other experienced only the ambient geomagnetic field. All measurements were conducted in a low-gradient, low-noise magnetics laboratory under well-maintained temperature conditions. This delay in regeneration was shown to be dependent on the planaria having a fixed orientation with respect to the magnetic field vectors. Results also indicate that this orientation-dependent transduction process does not result from Faraday induction but is consistent with a Ca2+ cyclotron resonance mechanism. Data interpretation also permits the tentative conclusion that the effect results from an inhibition of events at an early stage in the regeneration process before the onset of proliferation and differentiation.