Allergen immunotherapy inhibits airway eosinophilia and hyperresponsiveness associated with decreased IL-4 production by lymphocytes in a murine model of allergic asthma

Microelectrode recording methods for stereotactic localization of the subthalamic nucleus (STN) and surrounding structures are described. These methods accurately define targets for chronic deep brain stimulation in the treatment of Parkinson's disease. Mean firing rates and a burst index were determined for all recorded neurons, and responses to active and passive limb and orofacial movements were tested. STN neurons had a mean firing rate of 37+/-17 Hz (n = 248) and an irregular firing pattern (median burst index, 3.3). Movement-related activity and tremor cells were identified in the STN. Ventral to the STN, substantia nigra pars reticulata neurons had a mean rate of 71+/-23 Hz (n = 56) and a more regular firing pattern (median burst index, 1.7). Short trains (1-2 seconds) of electrical microstimulation of STN could produce tremor arrest but were not found to be useful for localization. Compared with data from normal monkeys our findings suggest that STN neuronal activity is elevated in Parkinson's disease.     

Spontaneous bursting activity of dopaminergic neurons in midbrain slices from immature rats: role of N-methyl-D-aspartate receptors

Dopamine neurons in midbrain coronal slices from adult rats (40-70 days old) discharged only in pacemaker-like mode. Irregular or bursting mode was never observed. In contrast, dopamine neurons in slices from immature rats (15-21 days old) exhibited not only pacemaker-like firing (53.4% of neurons), but also irregular and bursting patterns (28.3 and 18.3%, respectively). Glutamate and kainate increased the firing rate but failed to induce bursts in dopamine neurons from either adult or immature rats. N-Methyl-D-aspartate augmented the firing rate in all neurons from adult rats and produced a modest increase of bursts in only three out of 18 cells. In slices from immature rats, N-methyl-D-aspartate activated the discharge rate in all neurons and also induced bursts in 37 and 53% of pacemaker and irregular neurons, respectively, and increased the occurrence of spikes in bursts in 76% of spontaneously bursting neurons. The selective N-methyl-D-aspartate receptor antagonist (+/-)2-amino,5-phosphonopentanoic acid prevented N-methyl-D-aspartate-induced changes and also reduced spontaneous bursts, suggesting that bursting discharge is mediated by N-methyl-D-aspartate receptor activation. While pacemaker neurons from immature and from adult rats exhibited the same sensitivity to N-methyl-D-aspartate-induced stimulation of firing rate, spontaneously bursting neurons were more sensitive than pacemaker neurons from either immature or adult rats. The present study indicates that spontaneous bursting, dependent on N-methyl-D-aspartate receptor activation, is present, and may be induced, in dopamine neurons in slices from immature rats. Its absence from cells in slices from adult rats may reflect a reduced sensitivity of N-methyl-D-aspartate receptors on dopamine or the loss of the N-methyl-D-aspartate-activated burst generator.     

Recombinant human growth hormone decreases lung and liver tissue lipid peroxidation and increases antioxidant activity after thermal injury in rats

The effects of pulsed direct current (dc) electric fields on the frequency of spontaneous bursting in a model epileptic focus were studied. The high potassium hippocampal slice model was used to generate spontaneous burst firing activity similar to interictal spikes in the pyramidal cell layer of CA3. Electric fields were generated from platinum subdural electrodes placed in the perfusion bath. Three hundred and seventy-eight experimental trials were performed on 10 hippocampal slices from 10 rats and the effects of field polarity, field strength and duration of stimuli on firing frequency was examined. Hippocampal slices were oriented horizontally with the CA3 layer towards the positive electrode, the average interburst interval did not correlate significantly with polarity of the delivering pulses (one-way ANOVA, p = 0.96). Average interburst interval showed a significant correlation with pulse duration of 200 and 400 msec (p = 0.030 and p = 0.004, respectively). As a function of field strength, there were significant average interval changes for fields of 33, 46, and 73 mV/mm (p = 0.024, p = 0.001 and p = 0.001, respectively). In conclusion, CA3 burst firing activity in high potassium concentration can therefore be altered by electric fields.     

Alterations in pallidal neuronal responses to peripheral sensory and striatal stimulation in symptomatic and recovered parkinsonian cats

The spontaneous activity, responses to peripheral sensory and ipsilateral caudate nucleus stimulation of globus pallidus (GP) and entopeduncular nucleus (ENTO) neurons were studied in cats while normal, symptomatic for 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) induced parkinsonism, and when spontaneously recovered from gross parkinsonian motor deficits. Administration of MPTP resulted in parkinsonian motor symptoms that spontaneously recovered approximately 4-6 weeks after the MPTP administration. Post-mortem dopamine levels in recovered animals was approximately 95% below levels previously measured in normal animals. In symptomatic animals, the mean spontaneous firing rate for GP units was decreased by 50% and increased by 55% for ENTO units recorded. Spontaneous firing rates for GP and ENTO units in recovered cats were not significantly different from those observed in normal cats. In normal cats, 31.4% of GP and 29% of ENTO units tested responded to tactile stimulation of the face. Only 12.2% of GP and 13% of ENTO units responded to such stimulation in parkinsonian animals while the responses were generally less specific (larger receptive fields, more bilateral receptive fields, and more responses to multiple stimulation types) than normal. In recovered cats GP and ENTO responses resembled those observed in normal cats. There was no difference in the overall percentage of pallidal units responding to striatal stimulation across the 3 experimental conditions. There was, however, an increase in the percentage of units responding with complex response sequences (i.e. decrease in activity followed by an increase in activity) in symptomatic animals as compared to normal and recovered animals. The results suggest that loss of striatal dopamine in parkinsonian animals has profound effects on the sensory responsiveness of GP and ENTO neurons and that these effects coincide with the appearance of and recovery from parkinsonian motor deficits. These data further support the notion that sensory information processing by the basal ganglia may play an important role in influencing motor output.     

VTA dopamine neuron activity distinguishes alcohol-preferring (P) rats from Wistar rats

The mesolimbic dopamine (DA) system is innately deficient in rats selectively bred for high alcohol drinking behavior compared with rats selectively bred for low alcohol drinking and unselected rats. In alcohol-preferring (P) rats, compared with alcohol-nonpreferring (NP) rats, this is evidenced by fewer DA neurons in the ventral tegmental area (VTA) projecting to the nucleus accumbens (ACB). Yet, despite this deficiency, DA release in the ACB is similar in P, NP, and Wistar rats. DA release is regulated by DA neuronal activity, and DA neurons fire tonically as well as in bursts. Burst firing has been shown to substantially enhance DA release compared with tonic firing. The present study was designed to test the hypothesis that the remaining VTA DA neurons in P rats have faster firing frequencies and/or burst fire more frequently than VTA DA neurons in Wistar rats. The spontaneous activity of VTA DA neurons was recorded in unanesthetized alcohol-naive P and Wistar rats. A conventional burst analysis on 500 consecutive action potentials revealed that P rats had a significantly (p < 0.05) greater percentage of action potentials in bursts when compared with Wistar rats (P: 50.9%, Wistar: 34.4%). Firing frequency and other burst parameters (burst interspike interval, burst length, interburst interval, and the number of action potentials per burst) did not distinguish the two groups of rats. The increased burst activity in P rats may represent a compensatory mechanism to maintain adequate basal levels of DA despite the deficiency in the mesolimbic DA system.     

Cardiovirulent coxsackieviruses and the decay-accelerating factor (CD55) receptor

To determine the differences in behavioral effects between intrastriatal and intracerebroventricular glial cell-derived neurotrophic factor (GDNF) administration, spontaneous locomotor activity was measured after intrastriatal or intracerebroventricular injection of GDNF (10 microg) in normal adult rats with implanted guide cannulae. In addition, the distribution of GDNF after intracerebral injection was studied immunohistochemically. Intrastriatal administration of GDNF significantly increased rearing behavior 3-4 h after injection. Increases in all three aspects of locomotor activity (motility, locomotion, and rearing) were most pronounced 3 days after intrastriatal injection, and they lasted for several days. This hyperactivity was blocked by the selective dopamine D1 receptor antagonist SCH22390 and by the selective D2 receptor antagonist raclopride at doses of the dopamine receptor antagonists, which by themselves did not affect spontaneous locomotor activity. These results suggest that GDNF has both acute and long-lasting pharmacological effects on dopamine neurons in adult animals and stimulates locomotor activity by activating both dopamine D1 and D2 receptors. On the other hand, intracerebroventricular administration of the same dose of GDNF failed to increase locomotor activity at any time during the test period (12 days). The immunohistochemical study demonstrated widespread distribution of GDNF in the entire body of the striatum within 24 h after intrastriatal injection. It also revealed deep penetration of GDNF from the ventricular space into the brain parenchyma after intracerebroventricular injection. GDNF-immunoreactive neuronal cell bodies were seen in the ipsilateral substantia nigra pars compacta most frequently 6 h after intrastriatal injection. The number of such cell bodies after intracerebroventricular administration, on the other hand, was much lower than that seen after intrastriatal administration. Taken together, these data suggest that intrastriatal administration of GDNF is an effective approach for affecting DA transmission. Long-lasting behavior effects are mediated via dopamine D1 and D2 receptors. Higher doses of GDNF would probably be needed using the intracerebroventricular route as compared to intraparenchymal delivery to exert effects on the nigrostriatal system in Parkinson's disease patients.     

Immune function alterations in mice tolerant to delta9-tetrahydrocannabinol: functional and biochemical parameters

The present study examined (1) whether the neostriatum is involved in a drug-induced conditioned locomotor response and; (2) whether this structure participates in the development of behavioral sensitization. Moreover, the present study addressed the question whether the development of behavioral sensitization is necessary for the induction of conditioning. Rats received injections of either apomorphine (2 microg) or vehicle (solution of 0.1% ascorbate/saline) into the dorsal neostriatum daily for 7 days. These treatments were performed immediately prior to (apomorphine-paired group and vehicle group) or 30 min following (apomorphine-unpaired group) 10-min placement in an open field which served as the test environment. After a 3-day drug withdrawal period, the animals were given a 10-min non-drug vehicle test trial in the test environment. Three days later, a drug test with apomorphine was administered to the animals of the paired and unpaired treatment groups; the vehicle group again received an injection of vehicle. The analysis of locomotor activity in the open field (measured as the distance traversed) revealed that locomotor activity in the apomorphine-paired group was higher than in the other groups. There were no indications for behavioral sensitization to intrastriatal apomorphine, since the locomotor response in the apomorphine-paired group did not increase, but rather decreased with daily repeated injections of apomorphine. Furthermore, only the apomorphine-paired animals showed a higher locomotor response when tested after an intrastriatal injection of vehicle in the previously apomorphine-paired environment, which is indicative of a conditioned drug effect. These results suggest that the neostriatum is directly involved in the development of drug-induced conditioning of locomotor behavior but not in the establishment of behavioral sensitization.     

Intrastriatal infusion of lisuride--a potential treatment for Parkinson's disease? Behavioral and autoradiographic studies in 6-OHDA lesioned rats

The present study examined the effect of chronic intrastriatal infusion of the dopamine receptor agonist lisuride on apomorphine-induced rotational behaviour and on D2-dopamine receptors in rats with unilateral 6-hydroxydopamine (6-OHDA) lesions of the nigrostriatal dopaminergic pathway. The completeness of the lesion of the right ascending nigrostriatal dopaminergic pathway was confirmed by apomorphine-induced rotation and [3H]-mazindol autoradiography. The intrastriatal infusion of lisuride (0.5 microgram/h) into the lesioned striatum for 2 weeks induced an immediate but temporary spontaneous contralateral rotation and a reduction of apomorphine-induced rotation of 47.2% relative to pre-lisuride infusion. The density of D2-receptors in the lisuride-infused striatum was significantly decreased by 40% relative to vehicle-infused 6-OHDA lesioned rats. The level of D2-dopamine receptors returned to normal levels 3 weeks after the termination of lisuride infusion. These results show that the intrastriatal infusion of lisuride reverses the behavioural and D2-dopamine receptor changes present in the 6-OHDA lesion rat model of Parkinson's disease.     

Endoscopic features of the columnar-lined esophagus

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.     

Subthalamic nucleus neurons switch from single-spike activity to burst-firing mode

The modification of the discharge pattern of subthalamic nucleus (STN) neurons from single-spike activity to mixed burst-firing mode is one of the characteristics of parkinsonism in rat and primates. However, the mechanism of this process is not yet understood. Intrinsic firing patterns of STN neurons were examined in rat brain slices with intracellular and patch-clamp techniques. Almost half of the STN neurons that spontaneously discharged in the single-spike mode had the intrinsic property of switching to pure or mixed burst-firing mode when the membrane was hyperpolarized from -41.3 +/- 1.0 mV (range, -35 to -50 mV; n = 15) to -51.0 +/- 1.0 mV (range, -42 to -60 mV; n = 20). This switch was greatly facilitated by activation of metabotropic glutamate receptors with 1S,3R-ACPD. Recurrent membrane oscillations underlying burst-firing mode were endogenous and Ca2+-dependent because they were largely reduced by nifedipine (3 microM), Ni2+ (40 microM), and BAPTA-AM (10-50 microM) at any potential tested, whereas TTX (1 microM) had no effect. In contrast, simultaneous application of TEA (1 mM) and apamin (0.2 microM) prolonged burst duration. Moreover, in response to intracellular stimulation at hyperpolarized potentials, a plateau potential with a voltage and ionic basis similar to those of spontaneous bursts was recorded in 82% of the tested STN neurons, all of which displayed a low-threshold Ni2+-sensitive spike. We propose that recurrent membrane oscillations during bursts result from the sequential activation of T/R- and L-type Ca2+ currents, a Ca2+-activated inward current, and Ca2+-activated K+ currents.     

The elastic cartilage in the normal rat epiglottis. I. Fine structure

Unilateral electrolytic lesions of the locus coeruleus in rats result in spontaneous ipsiversive rotation, which is then replaced by contraversive rotation. One week after lesioning, when spontaneous turning ceases, apomorphine and d-amphetamine elicit contraversive circling behaviour, which was not affected by noradrenergic receptor blockade but was abolished by dopamine receptor blockade. The drug-induced contraversive circling response was also reproduced by piribedil but not clonidine. Combined unilateral electrolytic locus coeruleus and substantia nigra lesions on the same side resulted in apomorphine- and d-amphetamine-induced ipsilateral rotational behaviour which was indistinguishable from that seen with substantia nigra lesions alone. In rats with unilateral locus coeruleus lesions, the dose of intrastriatally injected apomorphine required to produce circling was less on the lesioned than the non-lesioned side. Direct injection of noradrenaline into one substantia nigra caused contraversive circling. Direct injection of phenoxybenzamine into one substantia nigra followed by apomorphine caused ipsiversive circling. The results suggest that the circling behaviour seen after unilateral locus coeruleus lesions depends on an asymmetry of striatal dopamine receptor activity and are consistent with a proposed coeruleus-nigral noradrenergic pathway, which enhances impulse flow in the dopaminergic nigrostriatal system.     

Spontaneous and drug-stimulated locomotor activity after the administration of pertussis toxin into the ventral tegmental area

Pertussis toxin (PTX) injected into the ventral tegmental area (VTA) produces an enhanced locomotor response to amphetamine. In the present study, we have evaluated the role of dopamine receptors on spontaneous locomotor activity and the enhanced locomotor response to dopaminergic agonists after the administration of PTX into the VTA. PTX injected into the VTA of rats produced a delayed increase in spontaneous locomotor activity with a latency of 4 d. This activity was markedly increased by day 6 and remained elevated for at least 28 d after PTX treatment. This increased spontaneous locomotor activity of PTX-treated animals was antagonized by the administration of the D1 receptor antagonist SCH23390 (0.03 and 0.1 mg/kg sc), but not by the D2 receptor antagonist eticlopride (0.1 and 0.3 mg/kg sc). After adaptation to the locomotor cages, the animals showed a markedly enhanced motor response to amphetamine (0.5 mg/kg ip) and apomorphine (5 mg/kg sc). The heightened locomotor responses to these dopaminergic agonists could be elicited for at least 2 mo after PTX administration. The enhanced response to amphetamine was antagonized by the administration of SCH23390 (0.03 and 0.1 mg/kg sc), but not by eticlopride (0.1 mg/kg). The increased response to apomorphine in PTX-treated animals was inhibited by SCH23390 (0.1 mg/kg sc) and partially inhibited by eticlopride (0.1 mg/kg sc). Both of these antagonists inhibited the spontaneous and the drug-induced locomotor responses in vehicle-treated control animals. These results suggest that the administration of PTX into the VTA leads to an increase in spontaneous and drug-induced locomotor activity in which D1 receptors seem to play an important role.     

Behavioral evaluation of the unilateral lesion model in rats using 6-hydroxydopamine. Correlation between the rotations induced by D-amphetamine, apomorphine and the manual dexterity test

INTRODUCTION: Evaluation of rotatory activity induced by dopaminergic agonists is the most widely used test of conduct for the measurement of dopaminergic depletion of a unilateral lesion of the striatonigral pathway caused by 6-hydroxydopamine (6-OHDA) in rats, since it is quantitatively related to the extension of the dopaminergic denervation. OBJECTIVE: The objective of this study was to evaluate, from different angles, the changes in conduct seen in the model of unilateral lesion with 6-OHDA and to establish correlation with the rotation induced by D-amphetamine and by apomorphine and the ladder test. MATERIAL AND METHODS: Male Wistar rats were used. Lesions were produced in the SNpc by stereotactic injection of 6-OHDA into the right hemisphere and the effectiveness of the lesions was studied using the rotary conduct induced by D-amphetamine and apomorphine. The motor ability of the front legs was measured by the ladder test, carried out under standard and forced conditions. RESULTS: All the animals with lesions had difficulty in reaching food with both legs, although the most pronounced deficit was in the leg contralateral to the lesion. The ladder test correlated better with rotatory activity induced by apomorphine than by D-amphetamine. CONCLUSION: The animals with most dopamine loss showed most deficient use of their front legs.     

beta-Phenylethylamine regulation of dopaminergic nigrostriatal cell activity

In the present paper, the action of beta-phenylethylamine on electrophysiological activity of dopaminergic nigrostriatal neurons is described. 10 s after its i.v. injection and during 2-4 min, beta-phenylethylamine decreased the firing rate, the number of spikes within and out of burst and the number of bursts per second of these neurons. This was a dose-related action with statistical differences starting from 1.4 mg/kg for total and out of burst firing rate and from 2.4 mg/kg for within burst firing rate and for the number of bursts per second. The standard deviation and the variation coefficient of inter-spike intervals increased in a dose-related way. The marked effect found after low-dose administration suggests that under physiological conditions endogenous beta-phenylethylamine levels regulate the nigrostriatal dopaminergic cell activity. After peripheral low dose administration, beta-phenylethylamine behaves as a dopaminergic agonist with a very fast and brief action.     

Enhancement of effects of dopaminergic agonists on neuronal activity in the caudate-putamen of the rat following long-term d-amphetamine administration

Amphetamine- and apomorphine-induced changes in the activity of neurons in the caudate-putamen of paralyzed, locally anesthetized rats were recorded in animals pretreated with 2.5 mg/kg d-amphetamine sulphate for 6, 18 or 36 days, or in animals pretreated with saline for 36 consecutive days. In saline-pretreated animals, 2.5 mg/kg d-amphetamine sulphate (IP) produced an initial, brief potentiation of neuronal firing that was followed by a marked depression of neuronal activity lasting for approximately 35 to 110 min after injection. In amphetamine-pretreated animals, this depression of neuronal activity to the same dose of the drug was markedly prolonged, especially in animals given 36 consecutive days of d-amphetamine pretreatment. A similar enhancement occurred in response to 0.25 mg/kg apomorphine (IP) in animals pretreated with amphetamine for 36 days compared to saline-pretreated control animals. These results are discussed in relation to the known behavioral and biochemical effects of acute and long-term amphetamine administration.     

Interaction between recovery from behavioral asymmetries induced by hemivibrissotomy in the rat and the effects of apomorphine and amphetamine.

Spontaneous and drug-induced turning behavior and thigmotactic scanning were tested either acutely (4–6 hr) or chronically (9 days) after unilateral removal of vibrissae in rats. Rats that were tested acutely scanned more with the intact vibrissae side. This asymmetry was reduced in rats that were tested chronically, indicating behavioral recovery. The indirect dopamine agonist amphetamine induced a reversed asymmetry after 9 days because the animals then scanned more with the side lacking the vibrissae. Postsynaptic doses of apomorphine administered to acutely tested rats induced more scanning with, and more turning toward, the intact vibrissae side. A negative correlation was found in the chronically tested rats between the asymmetry in spontaneous scanning and the asymmetry after apomorphine. Nonrecovered rats showed indications of a reversal after apomorphine. The results are discussed in relation to mechanisms of neural plasticity in the basal ganglia, such as receptor supersensitivity and changes in nigrostriatal afferents. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Effects of salicylate on neural activity in cat primary auditory cortex

The effect of systemically applied salicylate on single-unit firing activity in primary auditory cortex was investigated in six cats. A dose of 200 mg/kg sodium salicylate was administered intraperitoneally, and recordings from the same units were performed prior to application and continuously up to, on average. 6 h after administration. Local field potentials were used to track the threshold shifts and general input-output (I/O) behavior following salicylate administration. All animals showed 20-30 dB of threshold shift about 2 h after administration and showed no recovery during the following 4 h. I/O curves were invariably of the recruitment type. Significant changes were found in spontaneous firing rates for two groups of unit separately. Low-spontaneous rate units (initial firing rate < 1 spike/s) showed an increase in spontaneous rate and high-spontaneous rate units (initial firing rate > 1 spike/s) showed a decrease in spontaneous firing rate. There were no significant changes in modal and mean values for interspike-interval (ISI) histograms. The duration-to-rebound peak in the autocorrelation function for spontaneous firings was prolonged significantly after salicylate administration. Peak cross-correlation coefficients for the firing patterns of simultaneously recorded cells showed no significant change but the correlogram's central peak was significantly narrower after salicylate application. The percentage of firings occurring in bursts showed no significant change after administration of salicylate. The best modulation frequency in response to stimulation with periodic click trains decreased after administration. Both the changes in the spontaneous autocorrelogram and in the temporal modulation transfer function suggest a prolongation in the duration of the Ca(2+)-activated K+ conductance of the cortical pyramidal cells following salicylate. This suggests that salicylates affect both the auditory periphery and the auditory cortex.     

Chronic cold stress alters the basal and evoked electrophysiological activity of rat locus coeruleus neurons

In vivo extracellular single-unit recording techniques revealed that chronic cold stress significantly alters both the basal and the evoked electrophysiological activity of noradrenergic neurons in the locus coeruleus of the anaesthetized rat. Following 17-21 days of chronic cold exposure (5 degrees C), the single-unit activity of histologically-identified locus coeruleus neurons in chloral hydrate-anaesthetized rats was recorded and analysed in terms of their basal firing rate and pattern of spike activity, as well as their response to footshock stimulation. There was no significant difference in the incidence of spontaneously active cells/electrode track between cold-stressed rats and control rats. However, the basal spike activity of locus coeruleus cells recorded from cold-stressed rats differed significantly from that of control rats along two dimensions: i) they displayed significantly higher basal firing rates (mean = 1.88 Hz vs 1.20 Hz, respectively); and ii) they frequently exhibited spontaneous burst-firing activity that was not observed in control rats (observed in 15/17 cold-stressed rats vs 1/26 control rats). The evoked spike activity of locus coeruleus cells in cold-stressed rats also differed significantly from that of control rats along two dimensions: i) they were more likely to respond to footshock stimulation (mean = 90.3% vs 74.4%, respectively); and ii) these responses were more likely to consist of multispike bursts of action potentials (mean = 8 bursts/50 stimulations vs 1 burst/50 stimulations, respectively). These results indicate that alterations in the electrophysiological activity of noradrenergic locus coeruleus neurons may contribute to the phenomenon of stress-induced sensitization of norepinephrine release that is thought to underlie some of the neuropathological changes that accompany long-term stress.     

Postnatal differentiation of firing properties and morphological characteristics in layer V pyramidal neurons of the sensorimotor cortex

The maturational profile of the firing characteristics of 217 layer V pyramidal neurons of rat sensorimotor cortex, injected with biocytin for morphological reconstruction, was analysed by means of intracellular recordings made between postnatal day (P)3 and 22. Starting from the onset of the second postnatal week, the pyramidal neurons could be differentiated as adapting or non-adapting regular spiking on the basis of the presence or absence of spike frequency adaptation. The percentage of non-adapting regular spiking neurons was very high during the second postnatal week (53%) and progressively decreased with age, concurrently with the appearance of the new class of intrinsically bursting neurons (beginning of the third week) whose percentage progressively increased from 23%, found in P14-P16 rats, to 46% in adult rats. Non-adapting regular spiking neurons were found to share with intrinsically bursting neurons several physiological characteristics comprehending faster action potentials, more prominent effect of anomalous rectification and consistent depolarizing afterpotentials, that differentiated them from the adapting regular spiking neurons. Moreover, intrinsically bursting and non-adapting regular spiking neurons were characterized by a round-shaped distribution of basal dendrites and expanded apical dendritic arborization, that differentiated them from the adapting regular spiking neurons showing a simpler dendritic arborization. These morphological hallmarks were seen in immature intrinsically bursting neurons as soon as they became distinguishable, and in immature non-adapting regular spiking neurons starting from the onset of the second postnatal week. These findings suggest that a significant subpopulation of immature non-adapting regular spiking neurons are committed to becoming bursters, and that they are converted into intrinsically bursting neurons during the second postnatal week, as soon as the ionic current sustaining the burst firing is sufficiently strong. The faster action potentials in both immature non-adapting regular spiking and intrinsically bursting neurons suggest a higher density of Na+ channels in these neuronal classes: the maturational increase in Na+-current, namely of its persistent fraction, may represent the critical event for the conversion of the non-adapting regular spiking neurons into the intrinsically bursting ones.     

Isolation and comparison of natural and recombinant human CENP-A autoantigen

Previous studies have shown that administration of gamma-hydroxybutyric acid (GHBA) or the GABA(B) receptor agonist baclofen are associated with a decrease in firing rate, a regularisation of firing pattern and a decrease in burst activity of midbrain dopamine (DA) neurons in the substantia nigra (SN). In the present study we compared the ability of the novel GABA(B) receptor antagonist SCH 50911 and the selective antagonist of GHBA binding sites, NCS-382, to antagonise the effects of baclofen or GHBA, respectively, on the neuronal activity of DA neurons in anaesthetised rats. SCH 50911 (75 mg/kg, i.v.) was found to antagonise the decrease in firing rate, the regularisation of firing rhythm and the decrease of burst activity in DA cells, induced by baclofen (1-32 mg/kg, i.v.) or GHBA (12.5-1600 mg/kg, i.v.). NCS-382 (100 mg/kg, i.v.) did not affect the baclofen-induced changes in neuronal activity. Neither was the drug able to influence the GHBA-induced alterations in firing rate or in burst activity, although NCS-382 to some extent antagonised the regularisation of the firing pattern observed following low doses of GHBA (< or =100 mg/kg). The results of the present study give further support for the notion that the GHBA-induced changes in neuronal activity of nigral dopamine neurons are mediated by stimulation of GABA(B) receptors.