From: Robert Riedlinger [mailto:r_riedlin@telus.net]
Sent: 09 November 2004 02:35
To: repacholim
Cc: Art Thansandote; Imelda Oconnor
Subject: Sensitivity of Neurons to Weak Electric Fields
 
|
|
| |||||||
| |||||||||
Previous
Article | Next
Article 
Sensitivity of Neurons to Weak Electric Fields
1Krasnow Institute for Advanced Studies and Departments of 2Physics and Astronomy and 3Psychology, George Mason University, Fairfax, Virginia 22030, and 4Neuroscience Program, The George Washington University, Washington, DC 20037
 |
Abstract |
|---|
 Top Abstract IntroductionMaterials and MethodsResultsDiscussionReferences |
|---|
Weak electric fields modulate neuronal activity, and knowledge of the interaction threshold is important in the understanding of neuronal synchronization, in neural prosthetic design, and in the public health assessment of environmental extremely low frequency fields. Previous experimental measurements have placed the threshold between 1 and 5 mV/mm, although theory predicts that elongated neurons should have submillivolt per millimeter sensitivity near 100 µV/mm. We here provide the first experimental confirmation that neuronal networks are detectably sensitive to submillivolt per millimeter electrical fields [Gaussian pulses 26 msec full width at half-maximal, 140 µV/mm root mean square (rms), 295 µV/mm peak amplitude], an order of magnitude below previous findings, and further demonstrate that these networks are more sensitive than the average single neuron threshold (185 µV/mm rms, 394 µV/mm peak amplitude) to field modulation.
Key words: electric field; neuron; threshold; synchrony; ephaptic; hippocampus
|
Introduction |
|---|
| TopAbstractIntroductionMaterials and MethodsResultsDiscussionReferences |
|---|
Weak electric fields modulate neuronal activity (Jefferys, 1995
), and knowledge of the interaction threshold is
important in the understanding of neuronal synchronization, in
neural prosthetic design, and in the public health assessment of
environmental extremely low frequency (ELF) fields.
Previous experimental measurements have placed the threshold for
neuronal interaction with electric fields between 1 and 5 mV/mm
(field strength applied to tissue). In mammalian brain, direct
current (DC) electric fields 5-10 mV/mm cause changes in neuronal
evoked population spikes in hippocampal slices (Jefferys, 1981). In experiments that used both sinusoidal
input fields and added noise, stochastic resonance, Gluckman
et al. (1996b) detected field interactions as low as 2.5 mV/mm
root mean square (rms) in the CA1 region of the hippocampal
slice. More recently, Ghai et al. (2000) demonstrated the ability to modify
activity in low calcium hippocampal slices with electric fields as
low as 1 mV/mm.
Theory, however, predicts that elongated neurons should have
submillivolt per millimeter sensitivity (Weaver et al., 1998). Significant interaction with an electric
field requires an effect on cellular biochemical processes greater
than the "molecular shot noise" driven by macromolecular thermal
fluctuations. Based on an elongated neuron model with thermal
noise, the threshold for electric field interaction was estimated
near 100 µV/mm (Weaver et al., 1998).
The mammalian hippocampus has several unique features that render
it particularly sensitive to electric fields. Cellular packing
is so dense that it can display epileptiform events even in
the absence of functioning chemical synapses (Jefferys and
Haas, 1982; Taylor and Dudek, 1982), a condition under which electric fields
likely play a significant role in ensemble activity. Hippocampal
pyramidal cells have somata asymmetrically placed with respect to
their dendritic trees, and the sensitivity of a neuron to firing
rate modulation from an imposed electric field is related to the
amount of positional asymmetry of the soma with respect to the
dendritic tree (Chan and Nicholson, 1986; Chan et al., 1988). In addition, the individual pyramidal
cells are aligned such that adjacent cells have parallel dendrites,
which favor interaction with fields aligned along the collective
somatodendritic axes (Rushton, 1927). These oriented low amplitude effects are
distinct from the depolarization block seen with unoriented fields
of higher amplitude and frequency (Bikson et al., 2001).
In the experiments that are described here, we used a longitudinal hippocampal slice to maximize alignment of CA1 or CA3 neurons with the parallel electric field lines generated from parallel plate electrodes. We also used an electric field waveform with similarities to natural CA3 population extracellular fields, mimicking the low frequency characteristics of CA3 population activity local field potentials. We examined the effect of weak fields both on network responses and single neurons.
|
Materials and Methods |
|---|
| TopAbstractIntroductionMaterials and
MethodsResultsDiscussionReferences |
|---|
Slice preparation. Hippocampal slices were prepared from 45-to 80-d-old Sprague Dawley rats that were anesthetized deeply with diethyl-ether and decapitated. Slices (350 µm thick) were cut longitudinally with a tissue chopper and placed in an interface type perfusion chamber at 34°C. Consistently healthy longitudinal slices were obtained if slices were placed into the chamber at room temperature before being warmed with the temperature control circuit. Slices were perfused for 90 min with artificial CSF (ACSF) composed of (in mM): 155 Na+, 136 Cl-, 3.5 K+, 1.2 Ca 2+, 1.2 Mg 2+, 1.25 PO4 2-, 24 HCO3-, 1.2 SO42-, and 10 dextrose. To generate synchronous population events in the hippocampal slice, we then replaced the perfusate with elevated potassium ACSF containing 8.5 mM K+ and 141 mM Cl - (Rutecki et al., 1985
). Slices were allowed to acclimate to the
elevated K+ for 1-1.5 hr.
Recording methods. All neuronal activity was recorded with the
use of saline-filled micropipette electrodes (1-3 M
for recording population bursts and 9-15 M for single-unit recording), which were amplified
differentially (Grass model P16, Grass Instruments, Quincy, MA)
with respect to a saline agar bridge reference electrode (75 K). This bridge electrode contained agar prepared with
8.5 mM KCl as the solvent. To minimize the
stimulation artifact, we placed the reference electrode on an
isopotential of the applied field, manipulating it with respect to
the recording electrode to minimize a test sinusoidal electric
field (Gluckman et al., 1996b).
In the presence of elevated K+ the hippocampal slices exhibit
population burst firing activity in the CA3 region (Rutecki
et al., 1985). CA1 activity from longitudinal slices in
elevated K+ consists of smaller population events than
seen in CA3 and prominent single-unit activity. This differs from
transverse slice CA1 dynamics in elevated K+ because the
CA1 effectively is disconnected from the CA3 in this longitudinal
preparation. We used a simple threshold-crossing technique to
detect the onset times of the CA3 population bursts and CA1
neuronal activity. Single-unit spike extraction was performed with
Common Processing and Autocut software (DataWave Technologies,
Longmont, CO).
Electric field production. Slices were placed between two
field-generating Ag-AgCl parallel plate electrodes submerged in the
perfusate. The electric field was generated in the chamber from
driving current between two 12-mm-wide parallel Ag-AgCl plates,
spaced 17 mm apart, embedded within the chamber floor. To
compensate for electrode polarization, we feedback-controlled the
current that was applied by using a four-electrode technique (Fig. 1 A) such that the electrical
potential between two 1-mm-in-diameter sensing electrodes placed 12
mm apart was proportional to a control signal (Gluckman et al.,
2001). The resulting electric field in the
central 1 cm 2 region, where the slices were placed, was
mapped by using sinusoidal applied fields to establish electric
field uniformity and to calibrate the stimulation electronics. The
stimulation electronics were constructed such that the potentials
of the stimulation electrodes could float with respect to
measurement ground. The final current-generating stage was battery
powered, based on an Analog Devices Amp01 instrumentation amplifier
(Wilmington, MA), with an additional operational amplifier stage.
Additionally, the input stage of the stimulation amplifier
contained a zeroing offset, used to set the electric field to zero
when the control signal was zero. In practice, this offset was
adjusted at the beginning of each experiment until the
differentially measured potential difference between micropipette
electrodes placed within the chamber 5-10 mm apart in the direction
of the field was minimized, yielding a baseline DC field with a
magnitude <10 µV/mm.
|
To stimulate the slices, we used simulated burst stimulus waveforms (Fig. 1 F) that had a Gaussian profile (26 msec full width at half-maximal) and a low frequency spectrum with a similar distribution (Fig. 1C,D) to that of a CA3 population burst (Fig. 1 E). The stimulus waveform was generated at 10 kHz on a PC, producing an analog signal via a digital-to-analog circuit (M16-E National Instruments, Austin, TX). This analog signal was low-pass-filtered (<1.5 kHz) to reduce artifacts from the digital-to-analog conversion. Because such waveforms differ significantly from the typical square wave stimuli used in previous electric field threshold experiments, we will report both the peak amplitude and the rms amplitude of these simulated burst waveforms. The rms amplitude of stimulus waveforms was calculated over a window of 90 msec. All amplitudes that appear in the figures are in units of rms.
CA3 experimental protocol. In experiments conducted on the CA3, we chose slices that both exhibited robust population bursting and could be entrained fully by input fields with a maximum peak of 10 mV/mm. This excluded slices that were insensitive to electric field modulation, presumably because of the variability of the slicing procedure. Because of our alignment of the reference electrode along an isopotential, the stimulation artifacts from fields as large as 10 mV/mm were small with respect to the CA3 population burst activity and allowed for straightforward burst time extraction by using a simple threshold crossing. CA3 data were low-pass-filtered below 500-1000 Hz (recorded in true DC).
At the beginning of each CA3 experiment the mean interburst interval (IBI) of the slice was established over a 2 min period. A periodic input time series of simulated bursts was generated, with inter-event intervals 12% faster than the mean rate of the slice for slices with decreasing IBI and 10% faster for slices with increasing or stable IBI. The mean IBI rate of the slice was recalculated after each trial to ensure that the mean input frequency used for the stimulus remained faster than the new intrinsic mean of the slice. If after a trial the slice had a mean intrinsic IBI faster than that of the stimulus, then the data were discarded, because this implied that at some time during the experiment the rate of the input and slice were the same. Such identical frequencies would generate spurious cross-correlation, which could not be distinguished from true synchronization because of coupling between the two systems.
In an effort to reduce further the spurious cross-correlation because of shared frequency content, the phase of the input field was perturbed randomly (see Fig. 2 B) at least once per minute. Recordings during stimulation were 7 min in length, a time chosen as a compromise in obtaining sufficient data for statistical analysis while minimizing drift in the intrinsic mean IBI.
|
Sham experiments were conducted with the field electronics turned off and were interspersed with the field experiments. These sham experiments were used to generate statistical confidence limits for the field stimulation experiments.
CA1 experimental protocol. Experiments conducted on the CA1 were taken from slices that showed robust cellular activity in this region and that retained little or no anatomic CA3 after slicing. Such slices therefore were devoid of large-scale population burst firing events from the CA3, which minimized endogenous electric field or synaptic input to the CA1 that would have complicated interpretation of the results. Small spontaneous population responses and single-cell activity were observed. Stimulation frequency of 1-2 Hz was used for CA1 experiments.
All of the CA1 data were bandpass-filtered (250-2000 Hz) before data analysis. This bandpass served to capture multiple and single-unit activity well and, when applied to recordings of the stimuli from the chamber without a slice present, nearly eliminated the stimulus waveform. The same phase perturbations and sham experiments discussed above also were used for CA1 experiments.
However, because of the smaller signal-to-noise ratio of CA1 activity, we remained cautious of spurious stimulus artifacts and therefore generated two peri-stimulus time histograms (PSTHs) that used both upper and lower threshold crossings (Fig. 1 B). Because of the asymmetry of the input field with respect to zero voltage, we would expect mirror image changes in these two PSTH values from stimulus artifact contamination. The sum of these PSTHs was calculated for each bin so that field artifacts would sum to zero, giving distributions similar to the sham experiments. Biological activity that synchronized to the fields, either excitatory or inhibitory, would give asymmetric PSTH distributions after such dual-threshold PSTHs were combined.
|
Results |
|---|
| TopAbstractIntroductionMaterials and MethodsResultsDiscussionReferences |
|---|
CA3 activity
Raw data from a CA3 experiment are shown in Figure 2. In Figure 2, A and B, the top traces (thick lines) mark the timing of the stimulus field inputs, and the bottom trace (thin lines) shows the simultaneously recorded neuronal activity. At the beginning of the epoch shown in Figure 2A, the stimulus and CA3 activity start out of phase and remain unsynchronized for several stimulus cycles. This illustrates the subthreshold nature of small input fields, which are not able to produce arbitrarily large phase resets for the population bursts. However, once the stimulus phase comes into close alignment with the CA3 population phase, it captures and entrains the network (by pulse 4) at this field strength of 3.9 mV/mm rms (6.8 mV/mm peak). The residual stimulus artifact (SA) shown in Figure 2 is the largest we observed in these experiments after properly aligning the reference electrode close to an isopotential. The amplitude disparity between CA3 bursts and such residual SA made use of a simple threshold adequate to discriminate population firing times from SA in CA3 experiments without errors. Figure 2B illustrates data from the corresponding sham experiment in which the independent nature of the signals can be observed readily. An example of a phase perturbation (PP) is shown at the beginning of the epoch in Figure 2B.
Raster plots of the population events shown in Figure 2, A and B, are shown in Figure 2, C and D, respectively. It is clear that in Figure 2C the neuronal data are synchronized strongly to the stimulus input. Note that the neuronal activity escapes entrainment near the 45th stimulus, followed by steady advance of the phase difference between the stimulus and the neuronal activity until capture again is effected. No entrainment is seen in the raster plot from the sham experiment in Figure 2D. The raster plots in Figure 2 represent just over 3 min of recording.
CA3 synchronization at smaller field strengths from one experiment is illustrated in Figure 3. The left column demonstrates synchronization between an electric field stimulus and CA3 population burst activity with field strengths as low as 560 µV/mm rms (1.2 mV/mm peak amplitude) in Figure 3, E and G. On the right side of the figure are the corresponding sham experimental results. Figure 3, A and C, demonstrates strong synchronization at a field strength of 1.68 mV/mm rms (3.6 mV/mm peak), whereas the weaker synchronization remains visually evident in the raster and histogram plots in Figure 3, E and G. The dotted lines in Figure 3 indicate 2 SD above the mean histogram bin values.
|
To estimate the electric field threshold that would cause statistically
reliable synchronization, we examined all of the data from
slices that would synchronize completely with the input field at
a peak strength of 10 mV/mm. This relatively large field
(Terzuolo and Bullock, 1956; Jefferys, 1981; Gluckman et al., 1996a,b; Ghai et al., 2000) would synchronize more than one-half of
the slices that were tested.
For individual experiments (see supplementary data; available at www.jneurosci.org), significant consecutive histogram peaks just after stimulation were observed for three of 10 slices at 460 µV/mm rms (979 µV/mm peak). For random variables drawn from a normal distribution, consecutive histogram values >2SD should occur with frequencies <0.0025. We observed a significant consecutive histogram peak in only one of six experiments at 370 µV/mm rms (787 µV/mm peak).
Such simple threshold statistics do not reflect the broader histogram deviations just after stimulation, with values below 2 SD evident in these experiments. To better estimate a population threshold, we therefore pooled data from all of the experiments. The pooled and averaged results for 35 slices from six rats at a selection of field strengths are illustrated in Figure 4. In each panel the means (thin solid line) ± 2 SD (dashed lines) of the pooled and averaged sham experiments are indicated. We sought to match the number of bursts in the sham experimental groups to the number of bursts in the respective field experimental groups. If the total number of events in a given experimental group was less than the total number of sham events, we would resample the sham experiments randomly. Using the sham results to establish statistical confidence, we found that the lowest field strength that produced statistically significant pooled synchronization results in CA3 experiments was 370 µV/mm rms (787 µV/mm peak amplitude).
|
CA1 network activity
Synchronization between CA1
network activity and the electric field stimulus is illustrated in
Figure 5 for experiments from one slice. At the
top of the figure is an example of raw CA1 network data with small
population and multiunit activity (calibration 0.04 mV, 1000 msec),
stimulated with the Gaussian-shaped field indicated in the bottom
trace, with an excitatory field of 1.75 mV/mm rms. The expanded
insets show the Gaussian profile of the slight residual field
artifact and the increased CA1 network activity responding with
small time lags to the onset of each stimulus field. The raster
plots and histograms of the left column of Figure
5 illustrate an experiment in which the electric field was
excitatory (top left inset), and the right column illustrates data
in which the electric field was inhibitory (top right inset). Each
panel shows the mean ± 2 SD of the histogram (10 msec bins).
Evidence of synchronization is present for each field strength that
is shown. At the larger field strengths in Figure
5, the histogram peaks easily can be seen reflected in the
raster plots.
|
To estimate the electric field threshold limit that would cause statistically reliable synchronization, we examined all of the data from slices that would synchronize significantly with the input field at a peak strength of 1 mV/mm. This was in contrast to 10 mV/mm used for the CA3, because the CA1 was much more sensitive to electric fields. Almost every slice that exhibited robust CA1 cellular activity met this criterion.
For individual experiments (see supplementary data) significant consecutive histogram values just after stimulation were observed (from 6 slices) for three of five excitatory (+) and two of four inhibitory (-) experiments at 140 µV/mm rms (298 µV/mm peak).
Figure 6 shows the pooled and averaged results from 18 experiments on five rats, using seven slices with two field strengths: 290 µV/mm and 140 µV/mm (rms). The field orientations correspond to the excitatory (top) and inhibitory (bottom) orientations. In each plot the PSTHs are a combination of the upper and lower threshold crossings, with the mean ± 2 SD for event number-matched shams plotted as solid and dotted lines, respectively (sham data histograms are plotted as insets). The lowest field strength used that produced significant synchronization in these averaged CA1 experiments was 140 µV/mm rms (298 µV/mm peak amplitude).
|
CA1 single-unit activity
Figure
7A shows 10 sec of bandpass-filtered recording (250-2000
Hz) from an experiment observing a single unit in CA1 (further
illustrated in Fig. 8). Note the absence of stimulus
artifact. A single-unit trace is shown as an inset at an expanded
time base in Figure 7A. Figure 7B shows an overlay of all of the
first spike waveforms from the bursts from this experiment,
confirming that this was indeed a single unit.
|
|
Raster plots from two separate single-unit experiments are shown in Figure 8, A, B, E, and F, along with the corresponding PSTH in Figure 8, C, D, G, and H. Figure 8, E and G, demonstrates data from the solitary observed case of a single unit synchronizing with a field of 140 µV/mm rms (298 µV/mm peak amplitude), along with the corresponding sham experiment in Figure 8, F and H. Once again the dashed lines in the histograms are the mean histogram value ± 2 SD. Although frequent network synchronization was observed at this field strength, this was the only single unit observed to synchronize at such low field intensity.
For individual experiments (see supplementary data) significant consecutive histogram peaks just after stimulation were observed in three of 11 experiments of single-unit modulation at 185 µV/mm rms (394 µV/mm peak) and a single significant result for one of 14 slices at 140 µV/mm rms (298 µV/mm peak).
Most single units demonstrated burst firing activity as shown in Figure 7. If the electrodes were pushed against the cells during positioning, burst firing often would convert transiently to singlet activity. After electrodes were positioned, most cells would switch spontaneously from burst to singlet firing during recording at some point during the experiment, although burst firing remained the predominant mode of activity (>80%). Single-cell data were pooled from both singlet and burst firing modes, and all spikes were used for the analysis shown here. When only the first spike in a burst was used for analysis, the electric field interaction threshold appeared to be unchanged (data not shown).
Figure 9 illustrates averaged results for a selection of excitatory field strengths for CA1 single-unit activity. Event number-matched sham data averaged for each experimental group are indicated (thin lines) along with ± 2 SD of the sham mean (dashed lines). The lowest field strength that produced significant synchronization in pooled and averaged data (15 experiments on 4 rats, using 6 slices) was 185 µV/mm rms (393 µV/mm peak).
|
|
Discussion |
|---|
| TopAbstractIntroductionMaterials and MethodsResultsDiscussionReferences |
|---|
Our findings are the first experimental evidence that neurons are indeed capable of synchronizing to weak electric fields below 1 mV/mm, and our results demonstrate thresholds for electrical field interactions close to the best available theoretical limits. CA1 pyramidal cell networks were sensitive to fields with rms amplitudes as small as 140 µV/mm. In addition, we have shown the first experimental demonstration that neuronal networks appear to respond to fields with more sensitivity than single neurons.
We observed both excitation and suppression of network activity
in CA1 at the lowest field strengths that were used (140 µV/mm
rms). Such weak interaction thresholds are important for several
reasons: the potential use of weak electric fields for neuronal
modulation in prosthetic device design (Gluckman et al., 1996a, 2001; Ghai et al., 2000; Richardson et al., 2003), the environmental ELF field threshold for
interaction with biological systems (Adair, 1991; Weaver et al., 1998), or consideration of the significance of
endogenous field interactions within the intact nervous system
(Jefferys and Haas, 1982; Snow and Dudek, 1984a,b, 1986; Traub et al., 1985a,b; Dudek et al., 1986; Vigmond et al., 1997).
The CA1 networks were more sensitive to the electric fields than
the CA3 networks. Anatomic evidence suggests that the CA1 pyramidal
cells are more consistent in their total dendritic lengths from one
area of the CA1 to the next, in contrast to CA3 (Ishizuka et al.,
1995). The pyramidal cells of the CA1 region
also have a smaller extracellular-to-intracellular volume ratio
than that of the CA3 region (McBain et al., 1990), and such tight packing of neurons
increases the electrical impedance and field interactions between
cells (Vigmond et al., 1997).
The observation that weak perturbations can synchronize oscillatory
physical systems is centuries old (Huygenii, 1673). In vivo
measurements of hippocampal sharp waves can be as large as
8-14 mV/mm (Buzsaki, 1986), nearly two orders of magnitude larger
than needed to observe the effects seen in our experiments.
Our findings suggest that endogenous local field potentials
are large enough to play a role in the synchronization of neuronal
networks in the intact brain (Traub et al., 1985a,b). Because small fields can modulate
neuronal excitability in a subthreshold manner, network activity
could modulate the excitability of cells that are not spiking and
of cells not connected synaptically to the firing neurons producing
the electrical fields. Examples of place cells (Skaggs et al.,
1996) and odor recognition (Wehr and Laurent,
1996), in which the phase of the rhythmic local
field potential is important in neural encoding, are situations in
which endogenous electric fields could play a role.
Recent work predicts that the theoretical limit for the threshold
to detect a response in an elongated cell (25 x 1000 µm) to ELF electric fields would
be 
100 µV/mm (Weaver et al., 1998). This estimation is based on the assumption that
the electric field must produce effects larger than the stochastic
fluctuations relevant to biological membranes such as voltage-gated
ion channels and their associated ion fluxes, the so-called
molecular shot noise (Astumian et al., 1995). Our findings of a threshold for the CA1
networks and single cells between 100 and 200 µV/mm are the first
experimental data consistent with this predicted limit (Weaver et
al., 1998).
In addition, to our knowledge, this is the first demonstration
that neuronal networks respond to fields more sensitively than
single neurons. Whether this is a manifestation of simply
increasing the numbers of neuronal detectors or is from
array-enhanced signal detection caused by coupling (Linder et al.,
1995; Gailey, 2000; Krawiecki et al., 2000) remains to be determined.
We made no attempt to optimize the stimulus waveforms that were
used. Instead, we selected the field temporal profiles to mimic
naturally occurring population burst profiles from CA3. Optimizing
waveforms to incorporate neuronal resonant frequencies (Hutcheon
and Yarom, 2000) might decrease further the field strength
required to observe synchronization. The use of white noise
electric field stimulation with spike-triggered averaging of
the preceding electric field (Bryant and Segundo, 1976) could serve as a useful tool for
optimizing the electric field morphology.
Modulation by small fields has advantages in control devices
that use electric fields to modulate neuronal networks (Gluckman
et al., 2001; Richardson et al., 2003). Designing such devices to operate at the
smallest possible field strengths will minimize the potential for
unwanted functional effects or tissue damage from long-term chronic
stimulation.
Whether weak environmental ELF fields affect neuronal firing
will be a function of the reduction in ambient field by the
anatomic layers surrounding the brain and the neuronal modulation
threshold. Estimates suggest that typical ambient fields will
be attenuated below the thresholds we have determined (Adair,
1991). We view it as important to fill in two remaining
experimental gaps in our knowledge of ELF field effects: to verify
experimentally the predicted attenuation of fields and, in the
manner described here, to measure the synchronization threshold for
50-60 Hz fields.
|
Footnotes |
|---|
Received Mar. 20, 2003; revised May. 9, 2003; accepted May. 13, 2003.
This work was supported by National Institutes of Health Grants K02MH01493 and R01MH50006 and the Whitaker Foundation.
Correspondence should be addressed to Steven J. Schiff, Krasnow Institute, Mail Stop 2A1, George Mason University, Fairfax, VA 22030. E-mail: sschiff@gmu.edu.
J. T. Francis' present address: State University of New York Downstate Medical Center, Brooklyn, NY 11203.
Copyright © 2003 Society for Neuroscience 0270-6474/03/237255-07$15.00/0
|
References |
|---|
| TopAbstractIntroductionMaterials and MethodsResultsDiscussionReferences |
|---|
Adair RK (1991) Biological effects on the cellular level of electric field pulses. Health Phys 61: 395-399.[ISI][Medline]
Astumian RD, Weaver JC, Adair RK (1995) Rectification and signal averaging
of weak electric fields by biological cells. Proc Natl Acad Sci USA 92:
3740-3743.
Bikson M, Lian J, Hahn PJ, Stacey WC, Sciortino C, Durand DM (2001)
Suppression of epileptiform activity by high frequency sinusoidal fields in
rat hippocampal slices. J Physiol (Lond) 531: 181-191.
Bryant HL, Segundo JP (1976) Spike initiation by transmembrane current: a white-noise analysis. J Physiol (Lond) 260: 279-314.[Abstract]
Buzsaki G (1986) Hippocampal sharp waves: their origin and significance. Brain Res 398: 242-252.[ISI][Medline]
Chan CY, Nicholson C (1986) Modulation by applied electric fields of Purkinje and stellate cell activity in the isolated turtle cerebellum. J Physiol (Lond) 371: 89-114.[Abstract]
Chan CY, Houndsgaard J, Nicholson C (1988) Effects of electric fields on transmembrane potential and excitability of turtle cerebellar Purkinje cells in vitro. J Physiol (Lond) 402: 751-771.[Abstract]
Dudek FE, Snow RW, Taylor CP (1986) Role of electrical interactions in synchronization of epileptiform bursts. Adv Neurol 44: 593-617.[Medline]
Gailey PC (2000) Electrical signal detection and noise in systems with long-range coherence. In: Self-organized biological dynamics and nonlinear control (Wallenczek J, ed), pp 147-172. Cambridge, UK: Cambridge UP.
Ghai RS, Bikson M, Durand DM (2000) Effects of applied electric fields on
low-calcium epileptiform activity in the CA1 region of rat hippocampal slices.
J Neurophysiol 84: 274-280.
Gluckman BJ, Neel EJ, Netoff TI, Ditto WL, Spano ML, Schiff SJ (1996a)
Electric field suppression of epileptiform activity in hippocampal slices. J
Neurophysiol 76: 4202-4205.
Gluckman BJ, Netoff TI, Neel EJ, Ditto WL, Spano ML, Schiff SJ (1996b) Stochastic resonance in a neuronal network from mammalian brain. Phys Rev Lett 77: 4098-4101.[ISI][Medline]
Gluckman BJ, Nguyen H, Weinstein SL, Schiff SJ (2001) Adaptive electric
field control of epileptic seizures. J Neurosci 21: 590-600.
Hugenii C (1673) Horoloquim oscilatorium. Paris: Muguet. Reprinted in English as: The pendulum clock. Ames, IA: Iowa State UP, 1986.
Hutcheon B, Yarom Y (2000) Resonance, oscillation, and the intrinsic frequency preferences of neurons. Trends Neurosci 23: 216-222.[ISI][Medline]
Ishizuka N, Cowan WM, Amaral DG (1995) A quantitative analysis of the dendritic organization of pyramidal cells in the rat hippocampus. J Comp Neurol 362: 17-45.[ISI][Medline]
Jefferys JG (1981) Influence of electric fields on the excitability of granule cells in guinea-pig hippocampal slices. J Physiol (Lond) 319: 143-152.[Abstract]
Jefferys JGR (1995) Nonsynaptic modulation of neuronal activity in the
brain: electric currents and extracellular ions. Physiol Rev 75: 689-723.
Jefferys JGR, Haas HL (1982) Synchronized bursting of CA1 hippocampal pyramidal cells in the absence of synaptic transmission. Nature 300: 448-450.[ISI][Medline]
Krawiecki A, Sukiennicki A, Kosinski RA (2000) Stochastic resonance and noise-enhanced order with spatiotemporal periodic signal. Phys Rev E 62: 7683-7689.[ISI]
Linder JG, Meadows BK, Ditto WL (1995) Array-enhanced stochastic resonance and spatiotemporal synchronization. Phys Rev Lett 75: 3-6.[ISI][Medline]
McBain CJ, Traynelis SF, Dingledine R (1990) Regional variation of extracellular space in the hippocampus. Science 249: 674-677.[ISI][Medline]
Richardson KA, Gluckman BJ, Weinstein SL, Glosch CE, Moon JB, Gwinn RP, Gale K, Schiff SJ (2003) In vivo modulation of epileptiform activity with radial hippocampal electric fields. Epilepsia 44: 768-777.[ISI][Medline]
Rushton WAH (1927) The effect upon the threshold for nervous excitation of the length of nerve exposed, and the angle between current and nerve. J Physiol (Lond) 63: 357-377.
Rutecki PA, Lebeda FJ, Johnston D (1985) Epileptiform activity induced by
changes in extracellular potassium in hippocampus. J Neurophysiol 54:
1363-1374.
Skaggs WE, McNaughton BL, Wilson MA, Barnes CA (1996) Theta phase precession in hippocampal neuronal populations and the compression of temporal sequences. Hippocampus 6: 149-172.[ISI][Medline]
Snow RW, Dudek EF (1984a) Electrical fields directly contribute to action potential synchronization during convulsant-induced epileptiform bursts. Brain Res 323: 114-118.[ISI][Medline]
Snow RW, Dudek FE (1984b) Synchronous epileptiform bursts without chemical transmission in CA2, CA3, and dentate areas of the hippocampus. Brain Res 298: 382-385.[ISI][Medline]
Snow RW, Dudek FE (1986) Evidence for neuronal interactions by electrical field effects in the CA3 and dentate regions of rat hippocampal slices. Brain Res 367: 292-295.[ISI][Medline]
Taylor CP, Dudek FE (1982) Synchronous neural afterdischarges in rat hippocampal slices without active chemical synapses. Science 218: 810-812.[ISI][Medline]
Terzuolo CA, Bullock TH (1956) Measurement of imposed voltage gradient adequate to modulate neuronal firing. Physiology 42: 687-694.
Traub RD, Dudek FE, Taylor CP, Knowles WD (1985a) Simulation of hippocampal afterdischarges synchronized by electrical interactions. Neuroscience 14: 1033-1038.[ISI][Medline]
Traub RD, Dudek FE, Snow RW, Knowles WD (1985b) Computer simulations indicate that electrical field effects contribute to the shape of the epileptiform field potential. Neuroscience 15: 947-958.[ISI][Medline]
Vigmond EJ, Perez Velazquez JL, Valiante TA, Bardakjian BL, Carlen PL
(1997) Mechanisms of electrical coupling between pyramidal cells. J
Neurophysiol 78: 3107-3116.
Weaver JC, Vaughan TE, Adair RK, Astumian RD (1998) Theoretical limits on
the threshold for the response of long cells to weak extremely low frequency
electric fields due to ionic and molecular flux rectification. Biophys J 75:
2251-2254.
Wehr M, Laurent G (1996) Odour encoding by temporal sequences of firing in
oscillating neural assemblies. Nature 384: 162-166.[ISI][Medline]
This article has been cited by other articles:
|
|
 |
|
  M. Bikson, M. Inoue, H. Akiyama, J. K. Deans, J. E. Fox, H. Miyakawa, and J. G. R. Jefferys Effects of uniform extracellular DC electric fields on excitability in rat hippocampal slices in vitro J. Physiol., May 15, 2004; 557(1): 175 - 190. [Abstract] [Full Text] [PDF] |
|
|
| |||||
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| ~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~ | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||