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At least 847 records · Page 47Linked to original sources
PubMed2003

A model of reverse spike frequency adaptation and repetitive firing of subthalamic nucleus neurons.

Subthalamic nucleus neurons exhibit reverse spike-frequency adaptation. This occurs only at firing rates of 20-50 spikes/s and higher. Over this same frequency range, there is an increase in the steady-state frequency-intensity (F-I) curve's slope (the secondary range). Specific blockade of high-voltage activated calcium currents reduced the F-I curve slope and reverse adaptation. Blockade of calcium-dependent potassium current enhanced secondary range firing. A simple model that exhibited these properties used spike-triggered conductances similar to those in subthalamic neurons. It showed: 1) Nonaccumulating spike afterhyperpolarizations produce positively accelerating F-I curves and spike-frequency adaptation that is complete after the second spike. 2) Combinations of accumulating aftercurrents result in a linear F-I curve, whose slope depends on the relative contributions of inward and outward currents. Spike-frequency adaptation can be gradual. 3) With both accumulating and nonaccumulating aftercurrents, primary and secondary ranges will be present in the F-I curve. The slope of the primary range is determined by the nonaccumulating conductance; the accumulating conductances govern the secondary range. The transition is determined by the relative strengths of accumulating and nonaccumulating currents. 4) Spike-threshold accommodation contributes to the secondary range, reducing its slope at high firing rates. Threshold accommodation can stabilize firing when inward aftercurrents exceed outward ones. 5) Steady-state reverse adaptation results when accumulated inward aftercurrents exceed outward ones. This requires spike-threshold accommodation. Transient speedup arises when inward currents are smaller than outward ones at steady state, but accumulate more rapidly. 6) The same mechanisms alter firing in response to irregular patterns of synaptic conductances, as cell excitability fluctuates with changes in firing rate.

Adaptation, Physiological↗
PubMed2004

A combinatorial method for analyzing sequential firing patterns involving an arbitrary number of neurons based on relative time order.

Information processing in the brain is believed to require coordinated activity across many neurons. With the recent development of techniques for simultaneously recording the spiking activity of large numbers of individual neurons, the search for complex multicell firing patterns that could help reveal this neural code has become possible. Here we develop a new approach for analyzing sequential firing patterns involving an arbitrary number of neurons based on relative firing order. Specifically, we develop a combinatorial method for quantifying the degree of matching between a "reference sequence" of N distinct "letters" (representing a particular target order of firing by N cells) and an arbitrarily long "word" composed of any subset of those letters including repeats (representing the relative time order of spikes in an arbitrary firing pattern). The method involves computing the probability that a random permutation of the word's letters would by chance alone match the reference sequence as well as or better than the actual word does, assuming all permutations were equally likely. Lower probabilities thus indicate better matching. The overall degree and statistical significance of sequence matching across a heterogeneous set of words (such as those produced during the course of an experiment) can be computed from the corresponding set of probabilities. This approach can reduce the sample size problem associated with analyzing complex firing patterns. The approach is general and thus applicable to other types of neural data beyond multiple spike trains, such as EEG events or imaging signals from multiple locations. We have recently applied this method to quantify memory traces of sequential experience in the rodent hippocampus during slow wave sleep.

Algorithms↗
PubMed2006

5-HT2 receptor activation facilitates a persistent sodium current and repetitive firing in spinal motoneurons of rats with and without chronic spinal cord injury.

We examined the modulation of persistent inward currents (PICs) by serotonin (5-HT) in spinal motoneurons of normal and chronic spinal rats. PICs are composed of both a TTX-sensitive persistent sodium current (Na PIC) and a nimodipine-sensitive persistent calcium current (Ca PIC), and we focused on quantifying the Na PIC (and its action on the total PIC), which is known to be critical in enabling repetitive firing. Intracellular recordings were made from motoneurons of the whole sacrocaudal spinal cord of normal adult rats after the cord was acutely transected at the S2 spinal level (acute spinal rat condition), removed from the animal, and then maintained in vitro. In vitro motoneuron recordings were likewise made from rats that had a sacral spinal transection 2 mo previously (chronic spinal rats). In motoneurons from acute spinal rats, moderately high doses of 5-HT (> or = 10 microM), or the 5-HT2 receptor agonist DOI (> or = 30 microM), significantly increased the total PIC, hyperpolarized the PIC onset voltage, and hyperpolarized the spike threshold, whereas lower doses had no effect. Both 5-HT and DOI specifically increased the Na PIC portion of the total PIC (tested with nimodipine blocking the Ca PIC). Additionally, 5-HT, but not DOI, depolarized the resting membrane potential (Vm) and increased the input resistance (Rm) in a dose-dependent manner. Therefore 5-HT2 receptor activation facilitated the Na PIC, whereas other 5-HT receptors modulated Vm and Rm. Motoneurons of chronic spinal rats responded to 5-HT and DOI in the same way, but with larger responses and at much lower doses (0.3-1 microM), thus exhibiting a 30-fold supersensitivity to 5-HT. Specifically the Na PIC was supersensitive to 5-HT2 receptor activation with DOI. Also, Rm and Vm were supersensitive to 5-HT. Consistent with the known critical role of the Na PIC in repetitive firing, enhancement of the Na PIC by DOI or 5-HT facilitated the repetitive firing evoked by steady current injection and enabled repetitive firing in a subpopulation of motoneurons of acute spinal rats that were initially unable to produce sustained repetitive firing. We suggest that after spinal transection, residual endogenous spinal sources of 5-HT help facilitate the Na PIC and repetitive firing. With chronic injury, the developed 5-HT supersensitivity more than compensates for lost brain stem 5-HT, so that the Na PIC is large and motoneurons are very excitable, thus contributing to spasticity.

Amphetamines↗
PubMed2003

Distinct firing properties of higher order thalamic relay neurons.

It has been proposed that the thalamus is composed of at least two types of nuclei. First-order relay nuclei transmit signals from the periphery to the cortex while higher order nuclei may route information from one cortical area to another. Although much is known about the functional properties of relay neurons in first-order nuclei, little is known about relay neurons belonging to higher-order nuclei. We investigated the electrophysiological properties of relay cells in a higher-order thalamic nucleus using in vitro intracellular recordings from thalamic slices of the rat's lateral posterior nucleus (LPN). We found neurons of the LPN possess many of the same membrane properties as first-order relay neurons. These included low-threshold calcium spikes (IT) and burst firing, a mixed cation conductance (IH) that prevented membrane hyperpolarization, and a transient K+ conductance that delayed spike firing (IA). The repetitive firing characteristics of LPN neurons were more distinct. One group of cells, located in the more caudal regions of the LPN responded to depolarizing current pulses with a train of action potentials or in a regular spiking (RS) mode. This form of firing showed a steep but highly linear increase in firing frequency with increasing levels of membrane depolarization. Another group of cells, located in the more rostral regions of the LPN, responded to depolarizing current pulses with clusters of high-frequency bursts or in a clustered spiking (CS) mode. The overall firing frequency rose nonlinearly with membrane depolarization, but the frequency of a given burst remained relatively constant. The caudal LPN receives input from the superior colliculus, whereas the rostral LPN receives input from layers V and VI of the visual cortex. Thus the RS and CS cells may be driven by subcortical and cortical inputs respectively, and the distinct temporal properties of their response modes may be a necessary component of the LPN circuitry.

Action Potentials↗
PubMed2006

Effects of sodium pump activity on spontaneous firing in neurons of the rat suprachiasmatic nucleus.

Cell-attached and whole cell recording techniques were used to study the effects of electrogenic sodium pump on the excitability of rat suprachiasmatic nucleus (SCN) neurons. Blocking the sodium pump with the cardiac steroid strophanthidin or zero K+ increased the spontaneous firing of SCN neurons to different degrees with different recording modes, whereas turning the sodium pump into a nonselective cation channel with the marine toxin palytoxin invariably increased the spontaneous firing to the point of total blockade. Current-clamp recordings indicated that strophanthidin increased the rate of membrane depolarization and reduced the peak afterhyperpolarization potential (AHP), whereas zero K+ also increased the rate of depolarization, but enhanced the peak AHP. The dual effect of zero K+ was reflected by the biphasic time course of voltage responses to zero K+: an inhibitory phase with enhanced peak AHP and slower firing, followed by a delayed excitatory phase with faster rate of membrane depolarization and faster firing. In the presence of strophanthidin to block the sodium pump, zero K+ consistently decreased firing by enhancing the peak AHP. Repetitive applications of K+ -free solution gradually turned the biphasic inhibitory-followed-by-excitatory voltage response into a monophasic inhibitory response in cells recorded with the whole cell (but not the cell-attached) mode, suggesting rundown of sodium pump activity. Taken together, the results suggest that spontaneous firing of SCN neurons is regulated by sodium pump activity as well as the AHP, and that sodium pump activity is modulated by intracellular soluble substances subject to rundown under the whole cell conditions.

Acrylamides↗
PubMed1989

Repetitive firing properties of neurons in the ventral region of nucleus tractus solitarius. In vitro studies in adult and neonatal rat.

1. A brain stem slice preparation and intracellular techniques were used to examine the cellular properties of neurons within the ventral and ventrolateral region of the nucleus tractus solitarius (v-NTS) in adult and neonatal (3-12 days old) rats. These neurons are believed to be involved in the control of respiratory function. 2. On the basis of their active and passive electrophysiologic properties, cells in the v-NTS of adult rats were categorized into type A and type B neurons. Type A neurons fired spontaneously with rates ranging from 0.5 to 5 spikes/s at resting potential (-59.0 +/- 6 mV, mean +/- SD). When depolarized, type A cells responded with an initial high rate of firing, which rapidly declined to a steady state level. Spike-frequency adaptation (SFA) index (defined as steady state firing divided by peak activity x 100) was 40%, with a time constant for adaptation of 100-280 ms. When depolarized from membrane potentials more negative than resting, these neurons exhibited a silent period (up to 900 ms) before any spiking was observed (delayed excitation). The delay depended on the duration and magnitude of the hyperpolarizing prepulse that preceded depolarization. The action potentials of type A cells had a shoulder on the repolarization phase, measured 2-3 ms at one-half height, and increased in duration during repetitive firing. 3. At resting potential, type B neurons fired three to five times faster than type A. Although both type A and type B neurons showed spike-frequency adaptation, type B neurons adapted at a much faster rate than type A. The time constant for adaptation was 2-14 ms in type B cells. These cells displayed no delayed excitation on depolarization from membrane potentials more negative than rest. Some type B cells exhibited postinhibitory rebound (PIR) and depolarizing afterpotentials (DAPs). Both types A and B v-NTS neurons had comparable input resistance and showed inward rectification. 4. Neonatal v-NTS cells, in contrast to adult cells, belonged to a single population of neurons. Their resting membrane potential was -58 +/- 6.3 mV (mean +/- SD). The majority of these cells (30/34) were active (5-10 spikes/s) at rest. When depolarized, they showed an immediate increase in firing rate, which gradually slowed down to reach a steady state. Spike-frequency adaptation index was 59%, with a time constant for adaptation of 300-750 ms.(ABSTRACT TRUNCATED AT 400 WORDS)

Action Potentials↗
PubMed1990

Vertical eye movement-related secondary vestibular neurons ascending in medial longitudinal fasciculus in cat I. Firing properties and projection pathways.

1. The firing characteristics and projection patterns of secondary vestibular nucleus neurons involved in the vertical vestibuloocular pathways were investigated in alert cats. Single-unit recordings were made in the medial longitudinal fasciculus (MLF) near the trochlear nucleus from axons that were monosynaptically activated after electrical stimulation of the vestibular nerve. In a total of 253 identified secondary neurons, 225 discharged in relation to vertical eye movements; 189 of these increased their firing rate for downward eye movements and 36 for upward movements. The activity of the remaining 28 axons was not related to eye movements when the head was still. 2. Virtually all of the secondary neurons with downward on-direction displayed tonic activity that was primarily related to steady eye position during fixation (DPV neurons). The slope of the relationship between firing rate and vertical eye position ranged from 1.2 to 9.1 (spikes/s)/deg with a mean of 3.2 (spikes/s)/deg. The regularity of firing was quantified by calculating the coefficient of variation (CV) of interspike intervals. A comparison of the CV in the population units indicated that DPV neurons could be classified as either regular or irregular neurons. There was a tendency for regular neurons to have higher firing rates and higher correlation coefficients for the rate-position relationships than irregular neurons. 3. During pitch rotation in the light, all the DPV neurons tested increased their firing rate with upward head rotation. Both the phase and the amplitude of the response indicated that DPV neurons discharged not only in relation to eye position but also in relation to head velocity, suggesting that they received monosynaptic input from the posterior semicircular canal. The gain and phase lag of the response relative to head velocity were measured at 0.5 Hz. The range of the gain was 1.1-5.1 (spikes/s)/(deg/s), and that of the phase lag was 18.3-62.4 degrees. There was a tendency for irregular DPV neurons to have a larger gain and smaller phase lag than regular DPV neurons. 4. Ascending and descending projection pathways were determined for 147 DPV axons. Of these, 69 ascended in the contralateral MLF with respect to their soma (crossed-DPV axons), and 78 in the ipsilateral MLF (uncrossed-DPV axons), as revealed by their monosynaptic activation from the contralateral or ipsilateral vestibular nerve. Stimulation of the caudal MLF at the level of the obex evoked direct responses caused by antidromic activation of descending collaterals in approximately 70% (49/69) of the crossed-DPV axons.(ABSTRACT TRUNCATED AT 400 WORDS)

Action Potentials↗
PubMed1999

Convergent mechanosensory input structures the firing phase of a steering motor neuron in the blowfly, Calliphora.

The first basalar muscle (B1) is 1 of 17 small steering muscles in flies that control changes in wing stroke kinematics during flight. The B1 is often tonically active, firing a single phase-locked action potential in each and every wingbeat cycle. Changes in activation phase alter the biomechanical properties of B1, which in turn cause aerodynamically relevant changes in wing motion. The phase-locked firing of the B1 motor neuron (MNB1), is thought to arise from an interaction of wingbeat-synchronous inputs from the wings and from specialized equilibrium organs called halteres that beat antiphase to the wings and function to detect angular rotation of the body during flight. We investigated how the wing and haltere inputs interact to determine the firing phase of MNB1. Our results indicate that both wing and haltere afferents make strong monosynaptic connections with MNB1, consisting of fast electrical and slow Ca(2+)-sensitive components. Although both the wing and haltere-evoked excitatory postsynaptic potentials (EPSPs) display the two components, their relative contribution is different for the two inputs. Whereas the haltere-evoked EPSP is dominated by the fast electrical component, the wing-evoked EPSP is dominated by a large chemically mediated component and displays an additional prolonged Ca(2+)-dependent component that is absent in the haltere-evoked EPSP. Both inputs display an activity-dependent fatigue affecting both electrical and Ca(2+)-sensitive components, from which the haltere synapse recovers more rapidly. The net result of these synaptic differences is that the two pathways differ significantly in their relative ability to evoke action potentials in MNB1. Although the haltere pathway displays greater temporal precision, the wing pathway is stronger, judged by its ability to entrain MNB1 within a background of haltere stimulation. We propose a model by which these physiological differences play a functional role in tuning the firing phase of MNB1 during flight. The wing input may serve primarily to set the background firing phase of MNB1, whereas the haltere input serves to transiently advance the firing phase during equilibrium reflexes.

Animals↗
PubMed2002

Firing rate modulation of motoneurons activated by cutaneous and muscle receptor afferents in the decerebrate cat.

The aim of this study was to investigate whether activation of spinal motoneurons by sensory afferents of the caudal cutaneous sural (CCS) nerve evokes an atypical motor control scheme. In this scheme, motor units that contract fast and forcefully are driven by CCS afferents to fire faster than motor units that contract more slowly and weakly. This is the opposite of the scheme described by the size principle. Earlier studies from this lab do not support the atypical scheme and instead demonstrate that both CCS and muscle stretch recruit motor units according to the size principle. The latter finding may indicate that CCS and muscle-stretch inputs have similar functional organizations or that comparison of recruitment sequence was simply unable to resolve a difference. In the present experiments, we examine this issue using rate modulation as a more sensitive index of motoneuron activation than recruitment. Quantification of the firing output generated by these two inputs in the same pairs of motoneurons enabled direct comparison of the functional arrangements of CCS versus muscle-stretch inputs across the pool of medial gastrocnemius (MG) motoneurons. No systematic difference was observed in the rate modulation produced by CCS versus muscle-stretch inputs for 35 pairs of MG motoneurons. For the subset of 24 motoneuron pairs exhibiting linear co-modulation of firing rate (r > 0.5) in response to both CCS and muscle inputs, the slopes of the regression lines were statistically indistinguishable between the two inputs. For individual motoneuron pairs, small differences in slope between inputs were not related to differences in conduction velocity (CV), recruitment order, or, for a small sample, differences in motor unit force. We conclude that an atypical motor control scheme involving selective activation of typically less excitable motoneurons, if it does occur during normal movement, is not an obligatory consequence of activation by sural nerve afferents. On average and for both muscle-stretch and skin-pinch inputs, the motoneuron with the faster CV in the pair tended to be driven to fire at slightly but significantly faster firing rates. Computer simulations based in part on frequency-current relations measured directly from motoneurons revealed that properties intrinsic to motoneurons are sufficient to account for the higher firing rates of the faster CV motoneuron in a pair.

Action Potentials↗
PubMed2002

Integrate-and-fire neurons driven by correlated stochastic input.

Neurons are sensitive to correlations among synaptic inputs. However, analytical models that explicitly include correlations are hard to solve analytically, so their influence on a neuron's response has been difficult to ascertain. To gain some intuition on this problem, we studied the firing times of two simple integrate-and-fire model neurons driven by a correlated binary variable that represents the total input current. Analytic expressions were obtained for the average firing rate and coefficient of variation (a measure of spike-train variability) as functions of the mean, variance, and correlation time of the stochastic input. The results of computer simulations were in excellent agreement with these expressions. In these models, an increase in correlation time in general produces an increase in both the average firing rate and the variability of the output spike trains. However, the magnitude of the changes depends differentially on the relative values of the input mean and variance: the increase in firing rate is higher when the variance is large relative to the mean, whereas the increase in variability is higher when the variance is relatively small. In addition, the firing rate always tends to a finite limit value as the correlation time increases toward infinity, whereas the coefficient of variation typically diverges. These results suggest that temporal correlations may play a major role in determining the variability as well as the intensity of neuronal spike trains.

Action Potentials↗
PubMed2003

Synchronous firing and higher-order interactions in neuron pool.

The stochastic mechanism of synchronous firing in a population of neurons is studied from the point of view of information geometry. Higher-order interactions of neurons, which cannot be reduced to pairwise correlations, are proved to exist in synchronous firing. In a neuron pool where each neuron fires stochastically, the probability distribution q(r) of the activity r, which is the fraction of firing neurons in the pool, is studied. When q(r) has a widespread distribution, in particular, when q(r) has two peaks, the neurons fire synchronously at one time and are quiescent at other times. The mechanism of generating such a probability distribution is interesting because the activity r is concentrated on its mean value when each neuron fires independently, because of the law of large numbers. Even when pairwise interactions, or third-order interactions, exist, the concentration is not resolved. This shows that higher-order interactions are necessary to generate widespread activity distributions. We analyze a simple model in which neurons receive common overlapping inputs and prove that such a model can have a widespread distribution of activity, generating higher-order stochastic interactions.

Neurons↗
PubMed1998

Predicting the distribution of synaptic strengths and cell firing correlations in a self-organizing, sequence prediction model.

This article investigates the synaptic weight distribution of a self-supervised, sparse, and randomly connected recurrent network inspired by hippocampal region CA3. This network solves nontrivial sequence prediction problems by creating, on a neuron-by-neuron basis, special patterns of cell firing called local context units. These specialized patterns of cell firing--possibly an analog of hippocampal place cells--allow accurate prediction of the statistical distribution of synaptic weights, and this distribution is not at all gaussian. Aside from the majority of synapses that are, at least functionally, lost due to synaptic depression, the distribution is approximately uniform. Unexpectedly, this result is relatively independent of the input environment, and the uniform distribution of synaptic weights can be approximately parameterized based solely on the average activity level. Next, the results are generalized to other cell firing types (frequency codes and stochastic firing) and place cell-like firing distributions. Finally, we note that our predictions concerning the synaptic strength distribution can be extended to the distribution of correlated cell firings. Recent published neurophysiological results are consistent with this extension.

Electrophysiology↗
PubMed2006

Allopregnanolone reduces immobility in the forced swimming test and increases the firing rate of lateral septal neurons through actions on the GABAA receptor in the rat.

Since allopregnanolone reduces the total time of immobility in rats submitted to the forced swimming test, we decided to explore whether this neuroactive steroid shares other antidepressant-like actions, such as increasing the neuronal firing rate in the lateral septal nucleus (LSN). In order to discard the influence of the oestrous cycle on immobility and on the firing rate of LSN neurons, all Wistar rats used in the study underwent ovariectomy before treatments. A group of rats received different doses of allopregnanolone (0.5, 1.0, 2.0 and 3.0 mg/kg, i.p.) 1 hour before being forced to swim in order to identify the minimum effective dose diminishing immobility. None of the tested doses of allopregnanolone produced significant changes in motor activity in the open-field test. The minimum dose of allopregnanolone producing a significant reduction in the total time of immobility (p<0.05) against the vehicle was 1.0 mg/kg, while 2.0 mg/kg and above also increased the latency to the first period of immobility (p<0.05). The minimum effective dose of allopregnanolone reducing immobility in the forced swimming test (1.0 mg/kg) significantly (p <0.05) produced a higher (twofold) neuronal firing rate in LSN neurons, but did not produce any change in septofimbrial nucleus neurons, which fired at a rate similar to that of vehicle-treated rats. The pretreatment with the non-competitive GABAA receptor antagonist, picrotoxin (1.0 mg/kg), blocked the aforementioned actions of allopregnanolone on both immobility and LSN firing rate. In conclusion, allopregnanolone produces an antidepressant-like effect in the forced swimming test, associated with an increase in the LSN neuronal firing rate, seemingly mediated by the GABAA receptor.

Action Potentials↗
PubMed2006

Reduction of anion reversal potential subverts the inhibitory control of firing rate in spinal lamina I neurons: towards a biophysical basis for neuropathic pain.

BACKGROUND: Reduction of the transmembrane chloride gradient in spinal lamina I neurons contributes to the cellular hyperexcitability producing allodynia and hyperalgesia after peripheral nerve injury. The resultant decrease in anion reversal potential (i.e. shift in Eanion to less negative potentials) reduces glycine/GABAA receptor-mediated hyperpolarization, but the large increase in membrane conductance caused by inhibitory input can nonetheless shunt concurrent excitatory input. Without knowing the relative contribution of hyperpolarization and shunting to inhibition's modulation of firing rate, it is difficult to predict how much net disinhibition results from reduction of Eanion. We therefore used a biophysically accurate lamina I neuron model to investigate quantitatively how changes in Eanion affect firing rate modulation. RESULTS: Simulations reveal that even a small reduction of Eanion compromises inhibitory control of firing rate because reduction of Eanion not only decreases glycine/GABAA receptor-mediated hyperpolarization, but can also indirectly compromise the capacity of shunting to reduce spiking. The latter effect occurs because shunting-mediated modulation of firing rate depends on a competition between two biophysical phenomena: shunting reduces depolarization, which translates into reduced spiking, but shunting also shortens the membrane time constant, which translates into faster membrane charging and increased spiking; the latter effect predominates when average depolarization is suprathreshold. Disinhibition therefore occurs as both hyperpolarization- and shunting-mediated modulation of firing rate are subverted by reduction of Eanion. Small reductions may be compensated for by increased glycine/GABAA receptor-mediated input, but the system decompensates (i.e. compensation fails) as reduction of Eanion exceeds a critical value. Hyperexcitability necessarily develops once disinhibition becomes incompensable. Furthermore, compensation by increased glycine/GABAA receptor-mediated input introduces instability into the system, rendering it increasingly prone to abrupt decompensation and even paradoxical excitation. CONCLUSION: Reduction of Eanion dramatically compromises the inhibitory control of firing rate and, if compensation fails, is likely to contribute to the allodynia and hyperalgesia associated with neuropathic pain. These data help explain the relative intractability of neuropathic pain and illustrate how it is important to choose therapies not only based on disease mechanism, but based on quantitative understanding of that mechanism.

Animals↗
PubMed2005

Firing pattern and rapid modulation of activity by estrogen in primate luteinizing hormone releasing hormone-1 neurons.

We have shown previously that cultured LHRH-1 neurons, derived from monkey olfactory placode region, exhibit pulsatile LHRH-1 release at hourly intervals and spontaneous intracellular calcium oscillations, which synchronize at a frequency similar to LHRH-1 release. Brief application of estrogen induced a rapid increase in the frequency of intracellular calcium oscillations and the frequency of synchronizations. The estrogen-induced frequency of intracellular calcium oscillations was mediated by estrogen receptors (ER), whereas the frequency of synchronizations was not mediated by ER. In the present study, we further examined the rapid action of estrogen using patch-clamp recording in primate LHRH-1 neurons. Cell-attached patch-clamp recording showed that LHRH-1 neurons exhibited monophasic or biphasic action currents that were sensitive to an increase in extracellular K+ and the sodium channel blocker tetrodotoxin. The majority (90%) of LHRH-1 neurons showed irregular firing patterns composed of bursts and irregular beatings of action currents, which further formed a "cluster" firing pattern. Brief application of 17beta-estradiol (1 nM) increased the firing frequency and burst duration of LHRH-1 neurons with a latency of 60-120 sec for up to 25 min. ICI182,780, an ER antagonist, blocked the 17beta-estradiol-induced increase in the firing activity of LHRH-1 neurons. These results suggest that 1) primate LHRH-1 neurons exhibit complex firing patterns composed of activities with different time domains, 2) estrogen causes rapid stimulatory action of firing activity, and 3) this estrogen action is mediated by ER in primate LHRH-1 neurons.

Animals↗
PubMed2005

Androgens increase gonadotropin-releasing hormone neuron firing activity in females and interfere with progesterone negative feedback.

GnRH neurons are the central regulators of fertility, and their activity is modulated by steroid feedback. In women with hyperandrogenemic infertility and in animal models of these disorders, elevated androgen levels interfere with progesterone (P) negative feedback. Our previous work showed that steroids altered the frequency and amplitude of gamma-aminobutyric acid (GABA) transmission to GnRH neurons. Specifically, P inhibited GABA transmission, which can excite GnRH neurons, whereas dihydrotestosterone (DHT) increased GABA transmission. In this study the GnRH neuron firing rate was examined in the same animal models. Adult (>2 months) female mice were ovariectomized and treated for 8-12 d with implants containing estradiol (E), E and P, E and DHT, or E, P, and DHT. Targeted extracellular recordings were used to examine the long-term firing activity of green fluorescent protein-identified GnRH neurons in brain slices from these mice. In comparing E alone to E plus P animals, P increased the percentage of time that GnRH neurons were quiescent and reduced the area under the curve of the firing rate and the instantaneous firing frequency, suggesting that P provides additional negative feedback over E alone. The addition of DHT markedly increased GnRH neuron activity in both the presence and absence of P. DHT also altered the firing pattern of GnRH neurons, such that peaks in the firing rate detected by the Cluster8 algorithm were approximately doubled in frequency and amplitude. These data support and extend our previous findings and are consistent with the hypothesis that the changes in GABAergic transmission observed in these animal models impact upon the activity of GnRH neurons, and central androgen action probably stimulates GnRH release.

Algorithms↗
PubMed1986

Respiratory symptoms and annoyance in the vicinity of coal-fired plants.

This study constitutes one part of a program for assessing the impact of coal-fired power plants on the surrounding communities. A questionnaire was mailed to a total of 12,000 subjects living in six areas with coal-fired plants and in matched reference areas. The participation rate was 77.3%. In one coal-fired plant/reference area pair, a more detailed medical examination was carried out among subjects who reported symptoms of the respiratory tract. The match between coal-fired plant and reference areas was successful primarily in three pairs. Neither respiratory symptoms nor disease rates were increased among adults or children near any of these plants, but one plant seemed to give rise to annoyance. For the remaining coal-fired plants, consistently higher prevalences of respiratory tract symptoms and annoyance were observed in the surrounding population. The effects cannot, however, conclusively be related to the coal-fired plants. It should be pointed out that the air pollution levels were relatively low, also in the vicinity of most of the plants in this study.

Air Pollutants, Occupational↗
PubMed2006

Impaired firing and cell-specific compensation in neurons lacking nav1.6 sodium channels.

The ability of neurons to fire precise patterns of action potentials is critical for encoding inputs and efficiently driving target neurons. At the axon initial segment and nodes of Ranvier, where nerve impulses are generated and propagated, a high density of Na(v)1.2 sodium channels is developmentally replaced by Na(v)1.6 channels. In retinal ganglion cells (GCs), this isoform switch coincides with the developmental transition from single spikes to repetitive firing. Also, Na(v)1.6 channels are required for repetitive spiking in cerebellar Purkinje neurons. These previous observations suggest that the developmental appearance of Na(v)1.6 underlies the transition to repetitive spiking in GCs. To test this possibility, we recorded from GCs of med (Na(v)1.6-null) and wild-type mice during postnatal development. By postnatal day 18, when the switch to Na(v)1.6 at GC initial segments is normally complete, the maximal sustained and instantaneous firing rates were lower in med than in wild-type GCs, demonstrating that Na(v)1.6 channels are necessary to attain physiologically relevant firing frequencies in GCs. However, the firing impairment was milder than that reported previously in med Purkinje neurons, which prompted us to look for differences in compensatory sodium channel expression. Both Na(v)1.2 and Na(v)1.1 channels accumulated at initial segments and nodes of med GCs, sites normally occupied by Na(v)1.6. In med Purkinje cells, only Na(v)1.1 channels were found at initial segments, whereas in other brain regions, only Na(v)1.2 was detected at med initial segments and nodes. Thus, compensatory mechanisms in channel isoform distribution are cell specific, which likely results in different firing properties.

Action Potentials↗