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At least 397 records · Page 22Linked to original sources
PubMed1986

Hippocampal theta rhythm and the firing of neurons in walking and urethane anesthetized rats.

Recordings were taken from single neurons in the hippocampus and dentate gyrus of rats during walking and urethane anesthesia. Firing histograms for these cells were constructed as a function of the phase of the concurrent extracellularly recorded hippocampal slow wave theta rhythm. Care was taken to be sure of the site of recording of the theta rhythm and its phase with respect to a reliable reference, so that comparisons of the phases of firing could be made across animals. The firing of most of these neurons is deeply modulated as a function of the phase of the theta rhythm. This is true whether the theta rhythm occurs during walking or during urethane anesthesia, but for some types of cells the mean phases of firing are different in the two types of theta rhythm. During walking, pyramidal cells and interneurons in all hippocampal subregions and dentate granule cells have a maximum probability of firing near the positive peak of the theta rhythm recorded in the outer molecular layer of the dentate (dentate theta). During urethane anesthesia, the maximum firing probability for interneurons in CA1 and for dentate granule cells occurs near the negative peak of the dentate theta, while the phases of maximum firing for pyramidal cells and interneurons in CA3 and CA4 become widely distributed. The phases of maximum firing of pyramidal cells in CA1 are, if anything, more narrowly distributed around the positive peak of the dentate theta during urethane anesthesia than during walking. These differences in the firing of hippocampal cells during walking and urethane anesthesia represent some of the differences in cellular mechanisms distinguishing two kinds of hippocampal theta rhythm.

Action Potentials↗
PubMed1997

Patterns of neuronal firing in the human lateral thalamus during sleep and wakefulness.

The firing patterns of thalamic neurons in mammals undergo a dramatic change as the animal's state changes between sleep and wakefulness. During sleep the normal tonic firing of thalamic neurons changes into a slower bursting mode characterized by repetitive activation of a low-threshold calcium (Ca2+) current. The present report describes the patterns of thalamic neuronal firing during sleep and wakefulness in one human patient. Extracellular single neuron activity was recorded during functional stereotactic surgery in the thalamus of a patient with chronic pain, who was observed to fall asleep during the recording. Evolutive power spectra of the thalamic slow wave were used in place of cortical encephalography to confirm the patient's states of sleep and wakefulness. Twenty-nine sites were observed in motor and somatosensory thalamus (Vop, Vim, and Vc) that were characterized by the presence of neurons with bursting activity when the patient was asleep. Such bursting was not observed in the patient when she was awakened. At 14 of these sites we were able to discriminate the bursting activity of single units. In each case the cell stopped firing or its bursting was replaced by a tonic firing pattern when the patient was awakened. In three cases the patient began to lapse back into sleep and the neuron resumed firing in a bursting pattern once again. None of these units had a peripheral receptive field (RF), while several other units recorded in nearby regions that did not fire in a bursting pattern during sleep had kinesthetic or cutaneous RFs. Analysis of the intraburst firing pattern revealed increasing interspike intervals (ISI) for successive action potentials in a burst and that the duration of the first ISI in the burst decreased as the number of ISIs increased. This pattern is similar to that reported to occur as a result of a calcium spike. These data have confirmed for the first time that state-dependent changes in thalamic firing exist in the human and that the physiological substrates at the thalamic level that are involved in human sleep are similar to those observed in animals.

Adult↗
PubMed1997

Repetitive firing and oscillatory activity of pyramidal-like bursting neurons in the rat subiculum.

Electrophysiological characterization of neurons within the rat subiculum was carried out with intracellular recordings in an in vitro slice preparation. Subicular neurons responded to threshold pulses of depolarizing current delivered at a resting membrane potential (RMP) of 45.7+/-5.8 mV (mean+/-SD, n=85) with an initial burst of three to five fast action potentials that rode on a depolarizing envelope and was terminated by an afterhyperpolarization (burst AHP) (duration 113+/-35 ms; peak amplitude 2.7+/-0.6 mV, n=10). Tonic firing replaced the bursting mode at membrane potential less negative than -55 mV. Suprathreshold depolarizing pulses evoked at RMP both an initial burst and successive tonic firing. Intracellular staining with biocytin showed morphological features typical of pyramidal cells (n=8). The relationship between frequency of repetitive firing and injected current (f-I) revealed that the burst firing frequency (250-300 Hz) was only slightly influenced by the amount of injected current. By contrast, the f-I curve of the tonic firing phase depended upon current intensity: it displayed an initial segment that increased at first linearly and then turned into a plateau for both the early and the late inter-spike intervals. The frequency of the tonic firing declined only slightly with time, thus suggesting a lack of adaptation. During tonic firing, each single action potential was followed by a fast AHP and a depolarizing afterpotential. Termination of repetitive firing was followed by an AHP (spike-train AHP; duration 223+/-101 ms, peak amplitude 5.6+/-2.4 mV, n=17). Fast spike-train and burst AHPs were reduced by bath application of the Ca2+-channel blockers Co2+ (2 mM) and Cd2+ (1 mM) (n=8), thus suggesting the participation of Ca2+-dependent K+ conductances in these AHPs. Subicular bursting neurons generated persistent, subthreshold voltage oscillations at 5.3+/-1 Hz (n=20) during steady depolarization positive to -60 mV; at values positive to -55 mV, the oscillatory activity could trigger clusters of single action potentials with a periodicity of 0.9-2 Hz. Oscillations were not prevented by application of excitatory amino acid receptor and GABA(A) receptor antagonists (n=5), Ca2+-channel blockers (n=5), or Cs+ (3 mM; n=4), but were abolished by the Na+-channel blocker tetrodotoxin (1 microM; n=6). Our findings demonstrate that pyramidal-like subicular neurons generate both bursting and non-adapting tonic firing, depending upon their membrane potential. These neurons also display oscillatory activity in the range of theta frequency that depends on the activation of a voltage-gated Na+ conductance. These electrophysiological properties may play a role in the process of signals arising from the hippocampal formation before being funnelled towards other limbic structures.

Action Potentials↗
PubMed2003

Spike synchronization and firing rate in a population of motor cortical neurons in relation to movement direction and reaction time.

We studied the dynamics of precise spike synchronization and rate modulation in a population of neurons recorded in monkey motor cortex during performance of a delayed multidirectional pointing task and determined their relation to behavior. We showed that at the population level neurons coherently synchronized their activity at various moments during the trial in relation to relevant task events. The comparison of the time course of the modulation of synchronous activity with that of the firing rate of the same neurons revealed a considerable difference. Indeed, when synchronous activity was highest, at the end of the preparatory period, firing rate was low, and, conversely, when the firing rate was highest, at movement onset, synchronous activity was almost absent. There was a clear tendency for synchrony to precede firing rate, suggesting that the coherent activation of cell assemblies may trigger the increase in firing rate in large groups of neurons, although it appeared that there was no simple parallel shifting in time of these two activity measures. Interestingly, there was a systematic relationship between the amount of significant synchronous activity within the population of neurons and movement direction at the end of the preparatory period. Furthermore, about 400 ms later, at movement onset, the mean firing rate of the same population was also significantly tuned to movement direction, having roughly the same preferred direction as synchronous activity. Finally, reaction time measurements revealed a directional preference of the monkey with, once again, the same preferred direction as synchronous activity and firing rate. These results lead us to speculate that synchronous activity and firing rate are cooperative neuronal processes and that the directional matching of our three measures--firing rate, synchronicity, and reaction times--might be an effect of behaviorally induced network cooperativity acquired during learning.

Action Potentials↗
PubMed1989

Effect of norepinephrine, serotonin and tryptophan on the firing rate of sympathetic nerves.

The firing rate of sympathetic nerves innervating interscapular brown adipose tissue (IBAT) has been recorded following microinjection of monoamines into the ventromedial (VMN) and paraventricular nuclei (PVN). Microinjection of norepinephrine (10 nmol) into the paraventricular nucleus produced a biphasic pattern in the firing rate of the sympathetic efferent nerves to IBAT. There was an initial dose-related 20% inhibition of firing rate followed 2 min later by 10% increase above control. When 10 times as much norepinephrine was injected into the ventromedial hypothalamus, there was a small 5% decrease in firing rate and a later significant dose-related increase in firing rate. These effects of norepinephrine were blocked by phentolamine, an alpha-adrenergic blocking drug, but not by propranolol, a beta-adrenergic blocking drug. Injection of serotonin into the paraventricular nucleus produced a short-lived but significant increase in firing rate of sympathetic nerves to brown adipose tissue. Comparable amounts of serotonin injected into the ventromedial nucleus produced a similar magnitude of increase in firing rate which lasted longer. There was a clear dose-response effect of serotonin injected into the PVN, but a much less impressive response when serotonin was injected into the VMN. The response to injections of tryptophan in both the VMN and PVN was similar to those seen with serotonin. When serotonin or tryptophan were injected into the PVN and VMN simultaneously, there was a synergistic increase in sympathetic firing rate. These data are consistent with the hypothesis that both norepinephrine and serotonin can modulate sympathetic firing rate through interaction with neurons in either the VMN or PVN.

Action Potentials↗
PubMed1993

Characteristic firing behavior of cell types in the cardiorespiratory region of the nucleus tractus solitarii of the rat.

The present in vitro study was performed to characterize neurons within dorsal regions of the nucleus tractus solitarii (NTS), principally at the level of area postrema, and known to receive inputs predominantly from cardiovascular and respiratory afferents (i.e. cardiorespiratory NTS). This report describes 4 classes of neurons (S1-S4) that were silent at their resting membrane potential and received relatively short (< 3.6 ms) and consistent latency synaptic inputs (+/- 0.4 ms) comprising either an EPSP or EPSP/IPSP sequence following low intensity electrical stimulation of the solitary tract (ts). Intracellular recording with sharp electrodes were used to characterize neuron types based on their different firing response patterns to injection of depolarizing current. S1 cells showed a single action potential; S2 fired repetitively; S3 produced a 2-5 spike burst coincident with the start of the current pulse and S4 neurons showed delayed excitation. Accommodation of firing frequency was seen in S2, S3 and some S4 cells. The voltage dependency of the different discharge patterns of the 4 cell groups was tested by current pulse stimulation at different holding potentials. However, in the majority of cells in any one cell class the firing pattern was qualitatively similar. Based on these findings it is suggested that the different firing characteristics reflect differences in intrinsic membrane properties between neuron classes. Representative examples from each of the defined cell classes were further studied in current and voltage clamp using the whole cell patch technique to define the presence and role of certain ionic currents in the firing response patterns of the 4 cell groups. In the current clamp configuration the firing behavior of S1 neurons (single spiking) was unaltered during exposure to 4-aminopyridine (4-AP; 2 mM), cobalt chloride (Co; 5 mM), norepinephrine (NE; 20 microM) and muscarine chloride (50 microM). It is suggested that the relatively low excitability of this neuron is due a persistent outward current which occurred at -40 mV during depolarizing voltage steps in the voltage clamp configuration. A common characteristic of S2 neurons (repetitively firing) was that they showed accommodation during current injection which was greatly attenuated in the presence of Co or NE. In addition, 4-AP slowed the firing frequency, reduced the afterhyperpolarization and broadened the spike width of S2 cells. Interestingly, the amount of accommodation observed in S2 cells was variable for cells of this class and was proportional to the magnitude of a Co-sensitive inward current present during depolarizing voltage steps between -45 to -5 mV.(ABSTRACT TRUNCATED AT 400 WORDS)

4-Aminopyridine↗
PubMed1983

Effects of serotonin and morphine on spontaneous and evoked firing of nociceptive neurons in the trigeminal spinal nucleus of rats.

Spontaneously firing neurons that were responsive to noxious face pinch or noxious heat were studied in the trigeminal spinal nucleus of the rat brain. These neurons responded with either an increase or decrease in firing rate. In these neurons serotonin (5-hydroxytryptamine; 5-HT) apparently acts through two mechanisms to attenuate the response to a noxious stimulus. One mechanism is mimicked by morphine; these two drugs block the response to the noxious stimuli without having a consistent effect on spontaneous firing. The effects of the two drugs were somewhat selective depending on the noxious stimulus used and the effect of the noxious stimulus; morphine and 5-HT were more effective in blocking the increase in firing rate evoked by the face pinch but 5-HT and morphine were more effective in blocking the decrease in firing rate evoked by the noxious heat stimulus. Interestingly, the direction of the response to a particular noxious stimulus frequently predicted whether or not both morphine and 5-HT would act on the same or different neurons. A second mechanism by which 5-HT, but not morphine, acted was to change the spontaneous firing in a direction opposite that evoked by the noxious stimulus. This type of effect apparently modulated the response to a noxious stimulus by changing the spontaneous firing rate such that a noxious stimulus had to be more intense before it could significantly alter the neuronal firing in the opposite direction. Morphine occasionally produced a change in firing pattern in neurons; this effect remains to be documented more extensively.

Animals↗
PubMed1996

The burst-like firing of spinal neurons in rats with peripheral inflammation is reduced by an antagonist of N-methyl-D-aspartate.

Ankle inflammation was induced in rats by subcutaneous injection of complete Freund's adjuvant and the firing properties of spinal neurons receiving afferent input from the inflamed areas were studied four to six days later. Comparable neurons in normal rats were also studied. In normal animals the response of neurons to ankle compression consisted of a brief burst of action potentials followed by sustained firing during stimulus application. On cessation of the stimulus there was no prolonged afterdischarge. In rats with an inflamed ankle, compression of the ankle produced firing while the stimulus was applied, but with 17 of 22 neurons there was a prolonged (219 +/- 55 s) post-stimulus afterdischarge. All neurons studied in rats with peripheral inflammation fired with intermittent bursts of action potentials, particularly during the afterdischarge and spontaneous firing. The N-methyl-D-aspartate receptor antagonist DL-2-amino-5-phosphonopentanoate was ejected microiontophoretically near the cells studied. The major effect was a near abolition of bursts present in spontaneous firing and post-stimulus afterdischarges with a lesser reduction in firing during stimulus application. Effects on afterdischarge duration were variable. Since firing in bursts is known to increase transmitter release at some sites in the brain, it is proposed that when the relevant spinal neurons fire in bursts, additional intraspinal pathways are recruited and this contributes to the expanded receptive fields of neurons and possibly to the enhanced pain experienced by manipulation of inflamed peripheral tissues.

2-Amino-5-phosphonovalerate↗
PubMed2006

Sensitive dependence of the coefficient of variation of interspike intervals on the lower boundary of membrane potential for the leaky integrate-and-fire neuron model.

After the report of Softky and Koch [Softky, W.R., Koch, C., 1993. The highly irregular firing of cortical cells is inconsistent with temporal integration of random EPSPs. J. Neurosci. 13, 334-350], leaky integrate-and-fire models have been investigated to explain high coefficient of variation (CV) of interspike intervals (ISIs) at high firing rates observed in the cortex. The purpose of this paper is to study the effect of the position of a lower boundary of membrane potential on the possible value of CV of ISIs based on the diffusional leaky integrate-and-fire models with and without reversal potentials. Our result shows that the irregularity of ISIs for the diffusional leaky integrate-and-fire neuron significantly changes by imposing a lower boundary of membrane potential, which suggests the importance of the position of the lower boundary as well as that of the firing threshold when we study the statistical properties of leaky integrate-and-fire neuron models. It is worth pointing out that the mean-CV plot of ISIs for the diffusional leaky integrate-and-fire neuron with reversal potentials shows a close similarity to the experimental result obtained in Softky and Koch [Softky, W.R., Koch, C., 1993. The highly irregular firing of cortical cells is inconsistent with temporal integration of random EPSPs. J. Neurosci. 13, 334-350].

Action Potentials↗
PubMed2006

The effects of experimental neurolysis on ectopic firing in a rat chronic constriction nerve injury model.

PURPOSE: We studied the effects of experimental neurolysis on ectopic firing in a rat chronic constriction nerve injury (CCI) model. METHODS: Sixteen Wistar rats were used as CCI models; 8 in a neurolysis group and 8 in a sham operation group. Eight additional Wistar rats were used in a normal control group. The CCI model was created by loosely ligating the sciatic nerve with 4-0 chromic gut sutures. Seven days after surgery the same portion of the sciatic nerve, now embedded in scar tissue, was exposed. For the neurolysis group all sutures and scar tissue around the nerve were removed, and for the sham operation group only exposure of the sciatic nerve embedded in scar tissue was performed. Fourteen days after the first surgery the spinal cords of all animals in the 3 groups were transeated at the most rostral level of the spinal cord and ectopic firing was recorded antidromically from the sural nerve. The spontaneous ectopic firing frequency and the firing pattern at rest and the ectopic firing frequency under a hypoxic condition were analyzed. RESULTS: The ectopic firing frequency in the neurolysis group was significantly lower than that of the sham operation group but higher than that of the normal control group. Also the appearance rate of an on-off pattern was 0% in the neurolysis and normal control groups and 38% in the sham operation group. Finally the accumulated number of ectopic firings under a hypoxic condition was significantly smaller in the neurolysis and normal control groups than that of the sham operation group. CONCLUSIONS: Experimental neurolysis significantly improved the abnormal ectopic firing frequency and on-off firing pattern in the injured nerve of the CCI model. These findings may explain the efficacy of neurolysis on sensory symptoms such as numbness or spontaneous pain in chronic compression neuropathy.

Animals↗
PubMed1998

Self-sustained firing of human motor units.

Motoneurons of invertebrates and vertebrates can continue to fire repetitively after being activated by a brief, excitatory synaptic input (self-sustained firing). This firing behavior is due to the activation of intrinsic, voltage-gated currents which produce sustained regenerative depolarizations (plateau potentials) of the cell. Examination of these intrinsic cellular properties has been performed in reduced animal preparations and it is unknown if such self-sustained firing occurs in motoneurons of the intact human. In this paper, we present evidence of this in the human by using a technique of dual motor unit recordings. Subjects were instructed to maintain a constant dorsiflexion effort, and the common synaptic input (e.g. descending drive) onto the tibialis anterior (TA) motoneuron pool was monitored by recording the firing frequency of a low threshold 'control' unit. Once the firing rate of the control unit was constant, vibration of the TA tendon recruited a second 'test' unit which continued to fire after the vibration (i.e. synaptic input) was removed, even though the firing rate of the control unit (and thus, the common drive) remained the same or decreased. Self-sustained firing of motoneurons such as this may reduce the need for prolonged synaptic input when constant muscle activation is required (e.g. for postural tone).

Evoked Potentials, Motor↗
PubMed2003

Neurochemical and anatomical identification of fast- and slow-firing neurones in the rat dorsal raphe nucleus using juxtacellular labelling methods in vivo.

GABA neurones in the dorsal raphe nucleus (DRN) influence ascending 5-hydroxytryptamine (5-HT) neurones but are not physiologically or anatomically characterised. Here, in vivo juxtacellular labelling methods in urethane-anaesthetised rats were used to establish the neurochemical and morphological identity of a fast-firing population of DRN neurones, which recent data suggest may be GABAergic. Slow-firing, putative 5-HT DRN neurones were also identified for the first time using this approach. Fast-firing, DRN neurones were successfully labelled with neurobiotin (n=10) and the majority (n=8/10) were immunoreactive for the GABA synthetic enzyme glutamic acid decarboxylase. These neurones were located in the DRN (mainly lateral regions), and consistently fired spikes with short width (1.1+/-0.1 ms) and high frequency (12.1+/-2.0 Hz). In most cases spike trains were regular but displayed low frequency oscillations (1-2 Hz). These neurones were morphologically heterogeneous but commonly had branching axons with varicosities and dendrites that extended across DRN subregions and the midline. Slow-firing DRN neurones were also successfully labelled with neurobiotin (n=24). These neurones comprised a population of neurones immunopositive for 5-HT and/or tryptophan hydroxylase (n=12) that fired broad spikes (2.2+/-0.2 ms) with high regularity and low frequency (1.7+/-0.2 Hz). However, a slow-firing, less regular population of neurones immunonegative for 5-HT/tryptophan hydroxylase (n=12) was also apparent. In summary, this study chemically identifies fast- and slow-firing neurones in the DRN and establishes for the first time that fast-firing DRN neurones are GABAergic. The electrophysiological and morphological properties of these neurones suggest a novel function involving co-ordination between GABA and 5-HT neurones dispersed across DRN subregions.

Action Potentials↗
PubMed2001

Spontaneous burst-firing in three auditory cortical fields: its relation to local field potentials and its effect on inter-area cross-correlations.

Burst-firing refers to epochs of sharply elevated neural discharge. It has been suggested that correlated firing in different cortical areas in anesthetized animals results from spontaneous burst-firing related to electroencephalogram spindling activity and state of drowsiness. To investigate this, simultaneous recordings of spontaneous firings of neurons in the primary (AI), secondary (AII) and anterior (AAF) fields of the auditory cortex in the lightly anaesthetized cat were obtained. This allowed a study of bursting behavior in the three cortical areas under exactly the same anesthetic state. Burst occurrences were detected using the Poisson-surprise method, and were typically highly synchronized with local field potentials (LFPs) and with burst-firing of other neurons recorded on the same electrode. Burst-firing occurred in 85% of 371 units studied, and in 48 (15%) thereof there were at least 100 bursts per 15 min. Neurons in Al were bursting at a significantly higher rate, but with fewer spikes per burst, than units in AII. The average percentage of the time that a spontaneously firing neuron is in the bursting state is only about 3% (range 0.004, 29%). The average peak cross-correlation coefficients between spikes and LFP triggers were largest for burst-onset spikes, followed by those between all burst spikes and LFP triggers, and smallest when all spikes of the single unit were used in the correlation. This was the case for within- and between-area conditions. Burst-onset times in different auditory fields were not correlated. Thus, the major cause of the observed correlation of spontaneous firing in different cortical areas is not synchronous burst-firing.

Action Potentials↗
PubMed1999

Image analysis of gunshot residue on entry wounds. II--A statistical estimation of firing range.

A statistical investigation of the relationship between firing range and the amount and distribution of gunshot residue (GSR), used automated image analysis (IA) to quantify GSR deposit resulting from firings into pig skin, from distances ranging between contact and 45 cm. Overall, for a Ruger .22 semi-automatic rifle using CCI solid point, high velocity ammunition, the total area of GSR deposit on the skin sections decreased in a non-linear fashion with firing range. More specifically there were significant differences in the amount of GSR deposited from shots fired at contact compared with shots fired from distances between 2.5 and 45 cm; and between shots fired from a distance of 20 cm or less, with shots fired at a distance of 30 cm or more. In addition, GSR particles were heavily concentrated in the wound tract only for contact and close range shots at 2.5 cm, while the particle distribution was more uniform between the wound tract and the skin surfaces for shots fired from distances greater than 2.5 cm. Consequently, for future scientific investigations of gunshot fatalities, once standards have been established for the weapon and ammunition type in question, image analysis quantification of GSR deposited in and around the gunshot wound may be capable of providing a reliable, statistical basis for estimating firing range.

Animals↗
PubMed2003

The time first-response fire fighters have to initiate care in a midsize city.

The objective of this study was to determine whether simultaneously dispatched first-response firefighters (fire) arrive before transporting EMS providers (ambulance) and the amount of time fire has on scene to initiate care. Fire and ambulance dispatch records were obtained for all 9-1-1 responses from four 1-month intervals. Only incidents to which both agencies had been simultaneously dispatched were included. Response time for each agency was determined by subtracting the time of dispatch from the time of arrival. The difference between fire and ambulance response time was the time fire had to initiate care. Both agencies were simultaneously dispatched to 4752 incidents. Average response time for all incidents was 4.0 +/- 2.6 min for fire and 5.3 +/- 2.0 min for ambulance. Fire had 1.3 +/- 3.2 min on average to initiate care. Fire arrived before ambulance for 69% (3262) of requests and for these calls had 2.8 +/- 1.7 min on average to initiate care. Utilization of densely staged first-response fire apparatus in a midsize city may be appropriate because firefighters frequently arrive before ambulances and may have adequate time to initiate lifesaving interventions.

Ambulances↗
PubMed1998

The activation and composition of FiRE (an FGF-inducible response element) differ in a cell type- and growth factor-specific manner.

The expression of the heparan sulfate proteoglycan, syndecan-1, is induced both in keratinocytes and in fibroblasts during development and tissue regeneration. Here we report that in keratinocytes the syndecan-1 gene was stimulated by EGF but not by FGF-2. In fibroblasts it was stimulated by FGF-2 but not by EGF. Likewise, the recently discovered FGF-inducible response element (FiRE) on the gene of syndecan-1 was stimulated by FGF-2 in fibroblasts and by EGF in keratinocytes, but not vice versa. The FiRE has two binding sites for an activator protein-1 (AP-1), one for an FGF-inducible nuclear factor (FIN-1) and one for an upstream stimulatory factor-1 (USF-1). The growth factor-stimulated binding of these transcription factors, as well as their requirement for FiRE activation, varied between the two cell types. First, although AP-1s were required for activation of FiRE in both cell types, the binding of AP-1 to FiRE was increased by growth factor-stimulation only in fibroblasts and not in keratinocytes. Secondly, FiRE did not bind FIN-1 nor needed the FIN-1 binding site for EGF-stimulated activation in keratinocytes, in contrast to the FGF-stimulated activation of FiRE in fibroblasts. Thirdly, EGF, which did not activate FiRE in fibroblasts, failed to activate FIN-1 in these cells. Finally, an USF-1 binding site that was necessary for activation of FiRE in keratinocytes was not needed in fibroblasts. These data suggest mechanisms by which members of the EGF- and FGF-families can differentially stimulate transcription through AP-1 regulated elements in a cell type-specific manner.

3T3 Cells↗
PubMed2001

Effect of the selective noradrenergic reuptake inhibitor reboxetine on the firing activity of noradrenaline and serotonin neurons.

Reboxetine is a non-tricyclic antidepressant with selective noradrenergic (NA) reuptake-blocking effects. The effects of acute and sustained administration of reboxetine, on the firing activity of locus coeruleus NA neurons and dorsal raphe 5-HT neurons, were assessed using in vivo extracellular unitary recording in rats anaesthetized with chloral hydrate. Reboxetine (0.1-1.25 mg/kg, i.v.) dose-dependently decreased the firing activity of NA neurons (ED50 = 480 +/- 14 microg/kg). A 2-day treatment with reboxetine at 1.25, 2.5, 5, or 10 mg/kg per day (using osmotic minipumps implanted subcutaneously) produced significant decreases of 52%, 68%, 81%, and 83%, respectively, of NA firing activity. When the reboxetine treatment (2.5 mg/kg per day) duration was prolonged to 7 days, a 66% decrease in NA firing activity was observed which further decreased to 80% after 21 days of treatment. In contrast, 5-HT neuron firing rate remained unaltered following short- and long-term reboxetine treatments. The suppressant effect of the alpha2-adrenoceptor agonist clonidine on the firing activity of NA neurons was unchanged in long-term reboxetine-treated rats, but its effect on the firing activity of 5-HT neurons was blunted. The enhancement of NA firing activity by the 5-HT1A agonist 8-OH-DPAT was abolished in long-term reboxetine-treated rats, whereas, the inhibitory effect of the 5-HT2 agonist DOI was attenuated by about three-fold. In conclusion, sustained NA reuptake blockade by reboxetine lead to profound alterations in the function of NA neurons and of 5-HT receptors modulating their firing activity.

8-Hydroxy-2-(di-n-propylamino)tetralin↗
PubMed1998

Place cell discharge is extremely variable during individual passes of the rat through the firing field.

The idea that the rat hippocampus stores a map of space is based on the existence of "place cells" that show "location-specific" firing. The discharge of place cells is confined with remarkable precision to a cell-specific part of the environment called the cell's "firing field." We demonstrate here that firing is not nearly as reliable in the time domain as in the positional domain. Discharge during passes through the firing field was compared with a model with Poisson variance of the location-specific firing determined by the time-averaged positional firing rate distribution. Place cells characteristically fire too little or too much compared with expectations from the random model. This fundamental property of place cells is referred to as "excess firing variance" and has three main implications: (i) Place cell discharge is not only driven by the summation of many small, asynchronous excitatory synaptic inputs. (ii) Place cell discharge may encode a signal in addition to the current head location. (iii) The excess firing variance helps explain why the errors in computing the rat's position from the simultaneous activity of many place cells are large.

Action Potentials↗