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Clomipramine increases firing rate in lateral septal neurons related with hippocampus.

Long-term clomipramine administration (CMI: 2.5 mg/kg IP, 25 days) effects on 274 identified hippocampus-septal neurons was assessed in rats. Stimulation of CA 1/dentate areas produced a biphasic response in 61% of lateral septal neurons. A brief activation was followed by a period of suppression of firing. In CMI-treated rats, the neurons showing this biphasic response increased their firing rate about fourfold, while the suppression of firing shortened around threefold. Other septal neurons (36%), in which only the burst of activation appeared but not suppression of firing, did not change their firing rate even after long-term CMI. In conclusion, CMI produces an increase of firing rate in lateral septal neurons receiving inhibitory hippocampal influence which is likely to be mediated by a disinhibitory process.

Animals↗

The sequential-interval state space: a means of displaying temporal information in neuron firing.

Variability in neuronal firing exhibits sufficient uncertainty so that a simple average firing frequency code is probably inadequate for most nervous system signalling. Temporal patterns certainly play an important role in neuronal coding. We have used interval histogram and 3-dimensional sequential interval state space plots to investigate various common patterns of firing in neurons of the land snail, Helix aspersa. Typical firing patterns included random, highly regular, doublet, and burst firing. Individual neurons could be made to change their temporal firing pattern in response to changes in transmembrane currents, or temperature, or the application of convulsant drugs. In every instance, the sequential interval state space plot provided a more distinctive display of temporal pattern than did the more common interval histogram. State space plots were also investigated for evidence of a predicted chaotic attractor. In no instance was this type of state space plot observed.

Action Potentials↗

The ontogeny of repetitive firing and its modulation by norepinephrine in rat neocortical neurons.

The postnatal ontogeny of electrical properties was studied in rat sensorimotor cortical neurons (P6 to adult) using intracellular recording in an in vitro slice preparation. Many action potential properties and input resistance changed during the first 4 postnatal weeks. Repetitive firing behavior also changed during the first postnatal month. Spike-frequency adaptation was much stronger in immature neurons. At 1 week postnatal, the majority of cortical neurons would only fire for less than 200 ms regardless of the intensity of long depolarizing current injections. These cells were normal in other parameters and could fire throughout a depolarizing current injection in the presence of inorganic calcium channel blockers or norepinephrine (NE), suggesting that the inability to fire was not due to injury. The frequency with which we encountered cells with this extreme adaptation decreased with age. Spike-frequency adaptation in immature neurons appears to be primarily controlled by Ca-dependent K+ conductances as in mature neurons. In mature and immature neurons, three afterhyperpolarizations (AHPs) could be distinguished by their rate of decline. The fast AHP followed repolarization of a single spike and was only partially Ca- and K-dependent. The medium duration AHP was Ca-dependent and apamin-sensitive and the slow AHP was partially Ca-dependent and not blocked by apamin. NE decreased the slow Ca-dependent AHP via beta-adrenergic receptors. This effect of NE on AHPs appeared qualitatively similar throughout postnatal development. NE had a proportionately greater effect in younger neurons, however, due to their relatively larger slow AHP. The quantitative differences of NE's action on the slow AHP (sAHP) led to a qualitative difference in NE's effect on firing behavior. The effects of NE on firing behavior may therefore be greater during times critical for cortical maturation.

Action Potentials↗

Intracellular EGTA alters phasic firing of neurons in the rat supraoptic nucleus in vitro.

To determine the function of intracellular free Ca2+ which is important in generating the phasic firing pattern characteristic of vasopressin neurons in the supraoptic nucleus (SON), we injected the highly specific Ca(2+)-chelating agent ethyleneglycol-bis-(beta-aminoethyl ether) N,N-tetraacetic acid (EGTA) into SON cells in the rat hypothalamic slice preparation. Intracellular recordings from 29 SON neurons which showed phasic firing were analyzed. Of the 29 SON neurons, 21 were recorded with microelectrodes filled with 3 M potassium acetate and 20 of the 21 neurons retained the phasic pattern more than 1 h after penetration by the electrode. Only one neuron lost phasic firing and fired randomly. By contrast, in all 8 neurons which were recorded with microelectrodes filled with 100 mM EGTA/2 M potassium acetate, phasic firing disappeared 10-80 min after penetration of the recording electrode although the neurons still showed spontaneous activity. These neurons also lost the after hyperpolarization and plateau potentials which followed bursting discharges. Our results suggest that intracellular free Ca2+ may play an important role in generating phasic firing.

Action Potentials↗

The N-methyl-D-aspartate receptor and burst firing of CA1 hippocampal pyramidal neurons.

Previous intracellular investigations in the rat hippocampus have demonstrated that N-methyl-D-aspartate, ibotenate and 2,3-pyridine dicarboxylate (quinolinate) all evoke burst firing of CA1 pyramidal neurons, whereas kainate and quisqualate, which are thought to react with different receptors, do not. The purpose of the present study has been to investigate the ability of a series of compounds either to trigger burst firing or to antagonize this pattern of excitation. We report here that N-methyl-L-aspartate, 1,2-benzene dicarboxylate (phthalate) and methylene succinate (itaconate) are also capable of evoking burst firing. The results of this investigation suggest that since both quinolinate and phthalate are rigid planar molecules and only the 2 and 3 positioning of the carboxylates of pyridine was active, a cis configuration of the carboxyls with respect to the 2,3 carbon bond appears to be necessary for excitation. While a nitrogen atom is not necessary for activity (this is absent in phthalate and itaconate) a third functional group, bearing at least a partial positive charge, and in a position alpha to one of the carboxyl groups is required. The requirements for pyridine derivatives to trigger burst firing is similar to that reported as necessary for evoking convulsions and neurotoxicity after intrahippocampal infusion and a correlation between N-methyl-D-aspartate-like burst firing and depolarization and this neuropathology is considered. An important observation has been that the addition of a benzene ring to either quinolinate or phthalate to yield 2,3-quinoline dicarboxylate and 2,3-napthalene dicarboxylate, respectively, converted these excitants into antagonists of burst firing.(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acids↗

Background firing activity in guinea-pig neocortex in vitro.

The background firing activity was recorded extracellularly in experiments on guinea-pig neocortical slices maintained in vitro. The following types of background firing activity were revealed: (i) high regular single spikes (48%), (ii) irregular single spikes (15%), (iii) bursts (7%), (iv) groups (7%), (v) mixed activity where single spikes alternated with bursts or groups (28%). The specific interspike interval distribution and the specific shape of autocorrelogram corresponded to each of these background firing activity types. Furie analysis of autocorrelograms showed periodic components in spike sequences with the maxima at 3, 12, and 28 Hz. When blocking synaptic transmission with 100 mM adenosine, about 70% of the background active cells "fell silent" and the remaining 30% of neurons continued to generate action potentials. The latter seem to be actual spontaneously active neurons, i.e. they were capable of autonomous spike generation. We failed to find any correlation between the type of neuronal firing and the ability of neurons to be spontaneously active. The selective blockade of inhibitory synapses with 100 mM picrotoxine did not practically change the character of background firing activity though the responses to stimulation became epileptic. An important conclusion to emerge from this study is that the background firing activity in cortical slices can include the actual spontaneous discharges related to intrinsic cell properties as well as those concerned with synaptic actions. Furthermore, a small number of spontaneously active neurons seem to be able to synaptically activate twice the number of cells. The inhibitory interneurons did not significantly influence the propagation of excitation with the absence of stimulation.

Adenosine↗

Control of 40-Hz firing of reticular thalamic cells by neurotransmitters.

This study bears on the control exerted by neurotransmitters on the expression of a 40-Hz pacemaker activity observed in reticular thalamic cells. Experiments were conducted in urethane-anaesthetized rats using extracellular recordings and local applications of antagonists against the neurotransmitters involved in the modulation of reticular thalamic cells. All drugs were dissolved in a Ringer's solution (pH 7.4) and were applied in small quantities (25-150 nl) by pressure through one barrel of a micropipette assembly. Forty-Hertz firing was abolished by local application of the alpha 1 antagonist prazosin and by bilateral lesion of the locus coeruleus. Local applications of glutamate antagonists reduced the rate of discharges by 30-50% as did cortical cooling or complete transection of the internal capsule. Conversely, scopolamine exerted a permissive action on the expression of 40-Hz activities; many spontaneously bursting units started firing at 40 Hz under the influence of this muscarinic antagonist. Since reticular thalamic cells are GABAergic and synaptically coupled via axonal collaterals, we investigated how GABAergic drugs affected the regular firing of these cells. Local applications of bicuculline produced a transient increase of the firing rates while the application of GABA induced intermittent pauses on a background of regular discharges. The application of piperidine-4-sulphonic acid, a GABAA receptor agonist, produced a similar effect. The length of pauses generated by piperidine was statistically analysed. It was found that the duration of short pauses was a multiple integer of the mean interspike interval of surrounding discharges. The preservation of the period and phase of the rhythm across the pauses implies that a subthreshold oscillation was presented into the cells during the arrests of discharges. Given the mode of action of noradrenaline and acetylcholine on reticular thalamic neurons, and considering a possible metabotropic action of glutamate, the above results suggest that deactivation of a leaky K conductance is critically involved in the regular firing of these cells in urethane-anaesthetized rats. Alternatively, because reticular cells are coupled via inhibitory synapses, it is proposed that the 40-Hz firing frequency reflects, in the frequency domain, a point of equilibrium in the reticular thalamic network when the leaky K conductance is fully deactivated by the metabotropic effects of monoamines and/or excitatory amino acids.

2-Amino-5-phosphonovalerate↗

Limitation by gabapentin of high frequency action potential firing by mouse central neurons in cell culture.

The investigational anticonvulsant drug, gabapentin (GP; 1-(aminomethyl) cyclohexaneacetic acid) limited repetitive firing of sodium-dependent action potentials of mouse spinal cord and neocortical neurons in monolayer dissociated cell culture. The effect developed slowly over time with sustained exposure. The IC50 was 1.3 x 10(-4) M for exposure times < or = 60 s, 1.9 x 10(-5) M for 10-60 min, and 4.0 x 10(-6) M for 12-48 h. Hyperpolarization restored sustained firing in the continuing presence of GP. Blockade of action potential firing by GP was frequency (use)-dependent. After preincubation with 2.9 x 10(-5) M GP (5 micrograms/ml), trains of brief stimuli at > or = 50 Hz elicited fewer action potentials than in control solution. Also, at 150 Hz, maximal rate of rise of action potentials decreased progressively with repetitive firing in GP-containing, but not control, solution. After overnight incubation in 2.9 x 10(-5) M GP, the absolute refractory period was prolonged from 2.4 +/- 0.6 ms in control solution (n = 11) to 4.7 +/- 0.3 ms (n = 10; P = 0.02 vs. control), and complete recovery from inactivation was prolonged from 8.0 +/- 1.3 ms to 17.0 +/- 2.6 ms (P < 0.001 vs. control). These findings suggest that GP may alter function of voltage-activated sodium channels, but the mechanism is unproven and may be indirect. Limitation of firing was observed in > or = 50% of neurons at concentrations in the range of those found in plasma and cerebrospinal fluid of patients treated successfully with GP. These results suggest that limiting the rate of firing of sodium-dependent action potentials may contribute to the anticonvulsant efficacy of gabapentin.

Acetates↗

Community ecotoxicology: invertebrate emergence from Fire Trol 934 contaminated vernal pool and salt marsh sediments under contrasting photoperiod and temperature regimes.

Fire retardant chemicals are being used increasingly throughout the world to effectively manage wildland fires. The widespread use and high volume of retardant products being applied increase the potential for contamination of temporary wetlands that represent critical habitat for numerous species. This study aimed at assessing the emergence response of invertebrates from fire-retardant-contaminated sediments derived from two temporary wetlands, a vernal pool and a salt marsh, which differ distinctly in their invertebrate resting egg bank structure. Two application rates (1 and 3 Lm(-2)) of the commercially available fire retardant, Fire Trol 934, were used to simulate environmentally realistic contamination scenarios for wetlands situated in Mediterranean grasslands and shrublands, respectively. Two contrasting emergence conditions (winter versus spring flooding conditions) were simulated to take into account the high inter- and intra-annual variability of pond filling in Mediterranean areas. Results showed a decrease in abundance (p<0.001), taxonomic richness (p<0.001) and biodiversity based on Shannon-Weaver diversity indices (p<0.001) in both wetlands and under both emergence conditions with increased retardant application rate. This was due to the loss of chydorids, daphnids, ostracods, and rotifers in the vernal pool, and rotifers, nematodes, protozoa and aquatic fungi in the salt marsh. The observed patterns were similar for many taxa and community metrics at either retardant level irrespective of hatching regime, suggesting that the timing of pond filling was generally not an important influence in community response to Fire Trol. A multivariate approach to characterize community structure suggests that wetlands that undergo periodic drying are resilient to perturbations by chemicals and that community responses to anthropogenic stressors may be well within the range of response to natural disturbances.

Analysis of Variance↗

Firing pattern and calbindin-D28k content of human epileptic granule cells.

In the hippocampus of chronic temporal lobe epilepsy, many abnormalities in structure and function have been described but their pathophysiological relevance often is poorly understood. In this study, we asked whether there may be a link between changes in the firing pattern and the loss of the calcium binding protein calbindin-D28k in epileptic hippocampal granule cells. Using the perforated patch-clamp technique, we investigated granule cells in slices prepared from human hippocampi removed for the treatment of pharmacoresistant temporal lobe epilepsy. Granule cells in hippocampi without significant signs of structural damage (lesion group) displayed a firing pattern indistinguishable from that of rodent granule cells and were strongly labeled with anti-calbindin-D28k antibodies. In contrast, half of granule cells in sclerotic hippocampi (HS group) showed an altered firing pattern and a severe loss of calbindin-D28k. While these cells show passive membrane properties comparable to cells of the rodent and lesion group, they lack the medium afterhyperpolarization and display only a weak spike frequency adaptation. On the other hand, granule cells in the HS group have an increased action potential threshold and an enlarged fast afterhyperpolarization. Applying post-recording immunohistochemistry to individual electrophysiologically characterized granule cells, we show that the loss of calbindin-D28k is not causally related to any of the changes in firing pattern. Both alterations seem to occur during the course of temporal lobe epilepsy, with the firing pattern being affected earlier than the calbindin-D28k content. In conclusion, we propose that it is the combination of the altered intrinsic excitability of granule cells with the amplified and prolonged synaptic input from perforant path fibers previously described in the epileptic dentate area which promotes tonic, non-adapting, high frequency firing of granule cells and thereby strongly augments the excitability of the hippocampus.

Action Potentials↗

Interactions between low concentrations of ethanol and nicotine on firing rate of ventral tegmental dopamine neurones.

This study investigated interactions between ethanol and nicotine on dopamine-sensitive neurone firing in the ventral tegmental area (VTA), recorded in midbrain slices. No changes in spontaneous activity of the neurones were seen with nicotine at 10, 25, or 100 nM; at 250 nM there was a small significant increase in firing rate. Ethanol, applied alone, caused a significant increase in firing rate at 40 mM and at 60 nM but not at 20 mM. Combinations of 10 or 25 nM nicotine with 20 or 40 mM ethanol did not result in increased firing rates compared with either drug alone. However, nicotine 100 nM plus ethanol 60 mM significantly increased the rate of spontaneous firing compared with that after either drug alone at these concentrations. In contrast, nicotine at 250 nM plus ethanol at 60 mM did not increase firing rate, compared with each drug alone. Ketanserin, 2 microM, prevented the potentiating effect of nicotine 100 nM plus ethanol 60 mM. The results show synergism between ethanol and nicotine at specific concentrations that are likely to be present in the brain during the behavioural effects of these drugs, but the interaction is complex and may involve multiple drug actions.

Animals↗

Quetiapine increases the firing rate of rat substantia nigra and ventral tegmental area dopamine neurons in vitro.

The antipsychotic drug quetiapine increases the firing rate of dopamine neurons in the substantia nigra and the ventral tegmental area of the rat. In the present study we used an in vitro midbrain slice preparation and found that 3 microM quetiapine increases the firing rate of dopamine neuron in both structures by approximately 30%. The magnitude of the increase was not correlated with the basal firing rate of the dopamine neurons. In addition, quetiapine was not able to antagonize the inhibition of the firing evoked by the dopamine D2 receptor agonist quinpirole. Only with a very high concentration (30 microM), quetiapine was able to counteract the amphetamine-induced inhibition of the firing of the ventral tegmental area neurons; this effect was less pronounced in substantia nigra neurons. These findings indicate that the increase in firing rate induced by quetiapine cannot solely be mediated through an interaction with the dopamine D2-like autoreceptor present on the dopamine neurons.

Action Potentials↗

Comparison of injuries caused by the pistols Tokarev, Makarov and Glock 19 at firing distances of 10, 15 and 25cm.

Firings at cloth targets and at human skin from autopsy material were performed from the pistols 7.62 mm Tokarev (TT), 9 mm Makarov (PM) and 9 x 19 mm Glock 19 with common ammunition. The differences were in the soot deposit pattern, the degree of scorching of the synthetic fibres on the edges of the entrance hole and in the findings of the soot and the gunpowder particles. The results were similar on the cloth and on the skin targets. In the case of the TT and the PM, the soot deposit patterns reminded of a blossom or shafts of rays or fans, or the bullet wipe had four narrow and four wide sections regarding the number of lands and grooves. The TT left a large amount of soot and many gunpowder particles and caused the melting of the synthetic fibres on the edges of the entrance hole, producing a defect of the material 0.1-0.3 cm in diameter and defects of textile fibres around the entrance hole. In the skin the TT caused many intraepithelial tears, folds of the epidermis and recesses of the epidermis containing soot. Firings from the PM and the Glock 19 caused the melting only of the ends of individual synthetic fibres on the edges of the entrance hole. The PM left a large amount of soot and only a few gunpowder particles. The Glock 19 gave the least soot and the greatest number of gunpowder particles and also caused tears and recesses in the epidermis. Only in the case of the Glock 19, hexagonal or polygonal zones were seen in the soot deposit pattern. The differences in the soot pattern were more distinct at the firing distance of 10 cm. By increasing the distance from 10 to 15 cm, the intensity of soot diminished and began to disappear at 25cm, but remained more visible in the case of the TT. The gunpowder particles could be found in the epidermis and deeper in both layers of the dermis at all distances fired from the TT and the Glock 19. In the case of firings from the PM, at the distance 10 cm some of the gunpowder particles had penetrated into the dermis and most of them were in the upper layer of the dermis. At the firing distance of 15 and 25 cm, the gunpowder particles were only on and in the stratum corneum.

Firearms↗

Medial septal/diagonal band cells express multiple functional nicotinic receptor subtypes that are correlated with firing frequency.

The medial septum-diagonal band (MS/DB) contains primarily cholinergic and GABAergic neurons that project to the hippocampus, and are important for learning and memory. Whole-cell patch clamp methods with brain slices from p11--p20 rats were used to measure MS/DB cell responses to focal somatic application of 1mM acetylcholine (ACh) and a series of current pulses was applied in order to assess firing frequencies and the presence of hyperpolarization-activated currents (Ih). We identified three types of cells: (1) cells with fast inward currents blocked by methyllycaconitine (MLA) with slow firing rates (3--12 Hz), accommodating action potentials, and no Ih (n=20); (2) cells with currents that had both fast (MLA-sensitive) and slow components that were blocked with mecamylamine (MEC) that showed fast firing (up to 60 Hz) and slow firing (up to 3 Hz), with accommodating and non-accommodating action potentials (n=46), 33% of which had Ih; and (3) cells not responsive to ACh with moderate firing rates (10--42 Hz), some with accommodating action potentials and some without (n=19), of which 92% had Ih. These results are among the first to demonstrate functional nicotinic receptors in the MS/DB. The data suggest that these receptors include alpha 7 and non-alpha 7 subtypes and that the expression of each is correlated with firing frequency and the presence of Ih. Responses to ACh were not affected by tetrodotoxin (TTX) and CdC l(2) but were blocked by MLA or MLA and MEC, suggesting that these currents involve direct activation of nicotinic receptors.

Action Potentials↗

Place-selective firing of CA1 pyramidal cells during sharp wave/ripple network patterns in exploratory behavior.

We observed sharp wave/ripples (SWR) during exploration within brief (<2.4 s) interruptions of or during theta oscillations. CA1 network responses of SWRs occurring during exploration (eSWR) and SWRs detected in waking immobility or sleep were similar. However, neuronal activity during eSWR was location dependent, and eSWR-related firing was stronger inside the place field than outside. The eSPW-related firing increase was stronger than the baseline increase inside compared to outside, suggesting a "supralinear" summation of eSWR and place-selective inputs. Pairs of cells with similar place fields and/or correlated firing during exploration showed stronger coactivation during eSWRs and subsequent sleep-SWRs. Sequential activation of place cells was not required for the reactivation of waking co-firing patterns; cell pairs with symmetrical cross-correlations still showed reactivated waking co-firing patterns during sleep-SWRs. We suggest that place-selective firing during eSWRs facilitates initial associations between cells with similar place fields that enable place-related ensemble patterns to recur during subsequent sleep-SWRs.

Action Potentials↗

Oxytocin neurones are recruited into co-ordinated fluctuations of firing before bursting in the rat.

Hypothalamic oxytocin neurones have dual physiological functions with associated characteristic activity patterns: a homeostatic osmoregulatory role involving continuous low frequency firing at a relatively constant rate, and roles associated with reproduction involving periodic, brief, synchronised, high frequency bursts of spikes. Apparently the same neurones maintain both roles during reproduction, when both activity patterns occur simultaneously, although sometimes factors linked to the homeostatic response predominate and prevent bursting. With the object of understanding how oxytocin neuronal networks manage both roles during lactation, we analysed basal activity between bursts in simultaneously recorded neurones to reveal potentially adaptive changes in network behaviour. Negative autocorrelation on a time scale of 0.5-2 s occurs in basal activity between bursts but also in non-bursting oxytocin neurones, and can therefore be associated with the system's homeostatic role. Although the system responds to the pups suckling by the induction of bursting, there are also increasing fluctuations in firing that are positively correlated in some simultaneously recorded neurones during basal activity between bursts. A few seconds before bursts, cross-correlation strengthens, irregularity of firing increases, and serial correlation (autocorrelation) weakens, all substantially. After pharmacological treatments known to facilitate bursting, cross-correlation and irregularity of firing increase and autocorrelation weakens, and the reverse occurs in conditions that delay bursting (hyperosmotic stress and pharmacological interventions). Our analyses suggest heterogeneity in the population of oxytocin neurones during lactation; the range including 'leader neurones' that readily display co-ordinated fluctuations in firing in response to suckling and escape from negative autocorrelation just before bursts, and 'follower neurones' that fire at a relatively constant rate in no apparent relationship to others, except when recruited late to bursting, probably in response to massive stimulation from already bursting neurones. The steep increases in correlation a few seconds before bursts reflect an accelerating process of recruitment of follower neurones to co-ordinated fluctuations, leading to the phase transition that constitutes the critical stage of burst generation.

Acetylcholine↗

Control of firing by small (S)-alpha-amino-3-hydroxy-5-methyl-isoxazolepropionic acid-like inputs in hypothalamic gonadotropin releasing-hormone (GnRH) neurons.

Episodic release of gonadotropin releasing hormone (GnRH) is obligatory for mammalian reproduction. The contribution of synaptic input to intermittent firing of GnRH neurons is unclear. GnRH neurons have very few synapses and most post-synaptic currents are small. Therefore, the impact of synaptic currents on firing in GnRH neurons was directly examined using simulated (S)-alpha-amino-3-hydroxy-5-methyl-isoxazolepropionic acid (AMPA)-like inputs applied with the method of dynamic current clamping. Tightly synchronized inputs and 50 ms bursts of excitatory input resulted in action potentials that were coincident with the stimulus. Neither input pattern resulted in sustained firing. When ongoing patterns of simulated inputs were applied over a range of parameters, action potentials were associated with clusters of AMPA-like inputs of 250 pS (approximately 15 pA amplitudes), while single inputs of 500 pS (approximately 30 pA amplitudes) resulted in action potentials. Ongoing inputs of 500 pS drove firing at 4-9 Hz. These findings provide evidence that small, simulated glutamatergic inputs can control firing in GnRH neurons and suggest that despite the small amplitudes, endogenous synaptic input mediated by glutamate may contribute to firing in GnRH neurons.

Action Potentials↗

Scaling of prediction error does not confirm chaotic dynamics underlying irregular firing using interspike intervals from midbrain dopamine neurons.

Dopamine neurons in the substantia nigra pars compacta often fire in an irregular, single spike mode in vivo, and a similar firing pattern can be observed in vitro when small conductance calcium-activated potassium channel blockers are applied to the bath. It is not clear whether the irregular firing is due to stochastic processes or nonlinear deterministic processes. A previous study [Neuroscience 104 (2001) 829] used nonlinear forecasting methods applied to a continuous function derived from the interspike interval (ISI) data from irregularly firing dopamine neurons to show that the predictability scaled exponentially with forecast horizon and was consistent with nonlinear deterministic chaos. However, we show here that the observed exponential scaling is also consistent with a stochastic process, because it did not differ significantly from that of shuffled surrogate data. On the other hand, nonlinear forecasting directly from the ISI data using the package TISEAN provided some evidence for nonlinear deterministic structure in four of five records obtained in vitro and in two of nine records obtained in vivo. Although we cannot rule out a role for nonlinear chaotic dynamics in structuring the firing pattern, we suggest an alternate hypothesis that includes a mechanism by which the firing pattern can become more variable in the presence of a constant level of background noise.

Algorithms↗