Biomedical subjects

T Bal

Publications and source records attributed to T Bal.

16 recordsLinked to original sources

PubMed2000

Cortical feedback controls the frequency and synchrony of oscillations in the visual thalamus.

Thalamic circuits have an intrinsic capacity to generate state-dependent oscillations of different frequency and degrees of synchrony, but little is known of how synchronized oscillation is controlled in the intact brain or what function it may serve. The influence of cortical feedback was examined using slice preparations of the visual thalamus and computational models. Cortical feedback was mimicked by stimulating corticothalamic axons, triggered by the activity of relay neurons. This artificially coupled network had the capacity to self-organize and to generate qualitatively different rhythmical activities according to the strength of corticothalamic feedback stimuli. Weak feedback (one to three shocks at 100-150 Hz) phase-locked the spontaneous spindle oscillations (6-10 Hz) in geniculate and perigeniculate nuclei. However, strong feedback (four to eight shocks at 100-150 Hz) led to a more synchronized oscillation, slower in frequency (2-4 Hz) and dependent on GABA(B) receptors. This increase in synchrony was essentially attributable to a redistribution of the timing of action potential generation in lateral geniculate nucleus cells, resulting in an increased output of relay cells toward the cortex. Corticothalamic feedback is thus capable of inducing highly synchronous slow oscillations in physiologically intact thalamic circuits. This modulation may have implications for a better understanding of the descending control of thalamic nuclei by the cortex, and the genesis of pathological rhythmical activity, such as absence seizures.

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PubMed1999

Analog circuits for modeling biological neural networks: design and applications.

Computational neuroscience is emerging as a new approach in biological neural networks studies. In an attempt to contribute to this field, we present here a modeling work based on the implementation of biological neurons using specific analog integrated circuits. We first describe the mathematical basis of such models, then present analog emulations of different neurons. Each model is compared to its biological real counterpart as well as its numerical computation. Finally, we demonstrate the possible use of these analog models to interact dynamically with real cells through artificial synapses within hybrid networks. This method is currently used to explore neural networks dynamics.

Animals↗

PubMed1998

Periodicity of thalamic spindle waves is abolished by ZD7288,a blocker of Ih.

The actions of the novel bradycardiac agent ZD7288 [4-(N-ethyl-N-phenylamino)-1, 2-dimethyl-6-(methylamino)pyrimidinium chloride] were investigated on the hyperpolarization-activated cation current Ih and on network activity in spontaneously spindling ferret lateral geniculate (LGNd) slices in vitro using intracellular recording techniques. In voltage-clamp recordings, local application of ZD7288 (1 mM in micropipette) resulted in a complete block of Ih, whereas in current-clamp recordings, application of this agent resulted in an abolition of the depolarizing sag activated by hyperpolarization and decreased the frequency of intrinsic delta-oscillations for which Ih acts as a pacemaker current. In addition, block of Ih with ZD7288 resulted in an abolition of the afterdepolarization (ADP) that follows repetitive hyperpolarization and rebound burst firing as well as that occurring in between spindle waves. The block of the ADP was associated with a block of the spindle wave refractory period such that continuous 6- to 10-Hz oscillations were generated throughout the network. These findings give further support to the hypothesis that Ih is critically involved in the generation of slow rhythmicity in synchronized thalamic activity.

Animals↗

PubMed1997

Inhibitory interactions between perigeniculate GABAergic neurons.

Perigeniculate neurons form an interactive sheet of cells that inhibit one another as well as thalamocortical neurons in the dorsal lateral geniculate nucleus (LGNd). The inhibitory influence of the GABAergic neurons of the perigeniculate nucleus (PGN) onto other PGN neurons was examined with intracellular recordings in vitro. Intracellular recordings from PGN neurons during the generation of spindle waves revealed barrages of EPSPs and IPSPs. The excitation of local regions of the PGN with the local application of glutamate resulted in activation of IPSPs in neighboring PGN neurons. These IPSPs displayed an average reversal potential of -77 mV and were blocked by application of bicuculline methiodide or picrotoxin, indicating that they are mediated by GABAA receptors. In the presence of GABAA receptor blockade, the activation of PGN neurons with glutamate could result in slow IPSPs that were mediated by GABAB receptors in a subset (40%) of cells. Similarly, application of specific agonists muscimol and baclofen demonstrated that PGN neurons possess both functional GABAA and GABAB receptors. Examination of the axon arbors of biocytin-filled PGN neurons often revealed the presence of beaded axon collaterals within the PGN, suggesting that this may be an anatomical substrate for PGN to PGN inhibition. Functionally, activation of inhibition between PGN neurons could result in a shortening or a complete abolition of the low threshold Ca2+ spike or an inhibition of tonic discharge. We suggest that the mutual inhibition between PGN neurons forms a mechanism by which the excitability of these cells is tightly controlled. The activation of a point within the PGN may result in the inhibition of neighboring PGN neurons. This may be reflected in the LGNd as a center of inhibition surrounded by an annulus of disinhibition, thus forming a "center-surround" mechanism for thalamic function.

Acetazolamide↗

PubMed1997

Sleep and arousal: thalamocortical mechanisms.

Thalamocortical activity exhibits two distinct states: (a) synchronized rhythmic activity in the form of delta, spindle, and other slow waves during EEG-synchronized sleep and (b) tonic activity during waking and rapid-eye-movement sleep. Spindle waves are generated largely through a cyclical interaction between thalamocortical and thalamic reticular neurons involving both the intrinsic membrane properties of these cells and their anatomical interconnections. Specific alterations in the interactions between these cells can result in the generation of paroxysmal events resembling absence seizures in children. The release of several different neurotransmitters from the brain stem, hypothalamus, basal forebrain, and cerebral cortex results in a depolarization of thalamocortical and thalamic reticular neurons and an enhanced excitability in many cortical pyramidal cells, thereby suppressing the generation of sleep rhythms and promoting a state that is conducive to sensory processing and cognition.

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PubMed1997

Synchronized oscillations in the inferior olive are controlled by the hyperpolarization-activated cation current I(h).

The participation of a hyperpolarization-activated cationic current in the generation of oscillations in single inferior olive neurons and in the generation of ensemble oscillations in the inferior olive nucleus (IO) of the guinea pig and ferret was investigated in slices maintained in vitro. Intracellular recordings in guinea pig or ferret 10 neurons revealed that these cells could generate sustained endogenous oscillations (4-10 Hz) at hyperpolarized membrane potentials (-60 to -67 mV) after the intracellular injection of a brief hyperpolarizing current pulse. These oscillations appeared as the rhythmic generation of a low-threshold Ca2+ spike that typically initiated one or two fast Na+-dependent action potentials. Between low-threshold Ca2+ spikes was an afterhyperpolarization that formed a "pacemaker" potential. Local application of apamin resulted in a large reduction in the amplitude of the afterhyperpolarization, indicating that a Ca2+-activated K+ current makes a strong contribution to its generation. However, even in the presence of apamin, hyperpolarization of IO neurons results in a "depolarizing sag" of the membrane potential that was blocked by local application of Cs+ or partial replacement of extracellular Na+ with choline+ or N-methyl-D-glucamine+, suggesting that I(h) also contributes to the generation of the afterhyperpolarization. Extracellular application of low concentrations of cesium resulted in hyperpolarization of the membrane potential of IO neurons and spontaneous 5- to 6-Hz oscillations in single, as well as networks, of IO neurons. Application of larger concentrations of cesium reduced the frequency of oscillation to 2-3 Hz or blocked the oscillation entirely. On the basis of these results, we propose that I(h) contributes to single and ensemble oscillations in the IO in two ways: 1) I(h) contributes to the determination of the resting membrane potential such that reduction of I(h) results in hyperpolarization of the membrane potential and an increased propensity of oscillation through removal of inactivation of the low-threshold Ca2+ current; and 2) I(h) contributes to the generation of the afterhyperpolarization and the pacemaker potential between low-threshold Ca2+ spikes.

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PubMed1996

Are the interlaminar zones of the ferret dorsal lateral geniculate nucleus actually part of the perigeniculate nucleus?

The ferret dorsal lateral geniculate nucleus (LGNd) contains interneurons within the interlaminar zones situated between the laminae corresponding to the ipsi- and contralateral eyes. We found that a subset of these neurons exhibits electrophysiological properties similar to those previously reported for perigeniculate (PGN) neurons, including the generation of rhythmic sequences of rebound low-threshold Ca2+ spikes at a frequency of 1-4 Hz after the intracellular injection of a hyperpolarizing current pulse. These "PGN-like" interlaminar interneurons innervated restricted regions of the A-laminae, inhibited thalamocortical cells through GABAA, and perhaps GABAB, receptors, and were excited by axon collaterals from thalamocortical cells. This reciprocal relationship is identical to that formed by PGN cells and allowed the PGN-like interlaminar neurons to participate in the generation of spindle waves and other network oscillations. Pharmacologically, PGN-like interlaminar interneurons were also similar to PGN neurons: both generated a prolonged depolarization in response to the local application of serotonin, 1S,3R-ACPD, and CCK8S, and a rapid depolarization followed by a more prolonged hyperpolarization in response to acetylcholine. Examination of parvalbumin and calbindin staining in the ferret LGNd revealed that both PGN and a subset of interlaminar neurons were parvalbumin-positive. In contrast, calbindin-positive cells were relatively absent in the PGN and sparsely present in the interlaminar zones, but were numerous in the A and C laminae. Our results indicate that the interlaminar zone in between laminae A and A1 and A1 and C in the ferret LGNd possesses a cell type that is electrophysiologically, pharmacologically, anatomically, immunocytochemically, and functionally similar to neurons in the PGN.

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PubMed1996

What stops synchronized thalamocortical oscillations?

Slow-wave sleep as well as generalized absence seizures are characterized by the occurrence of synchronized oscillations in thalamocortical systems that spontaneously appear and disappear. The spontaneous appearance of synchronized oscillations results from the initiation by one or a small number of cells followed by the progressive recruitment of large numbers of neighboring neurons into the synchronized network activity. Synchronized network oscillations representative of slow-wave sleep, as well as absence seizures, were demonstrated to cease spontaneously at least in part through the persistent activation of a hyperpolarization-activated cation conductance. Block of this conductance resulted in oscillations that, once generalized, occur continuously. These results indicate that the persistent activation of a hyperpolarization-activated cation conductance is a key mechanism through which synchronized oscillations in thalamocortical networks normally terminate.

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PubMed1996

Ionic mechanisms underlying synchronized oscillations and propagating waves in a model of ferret thalamic slices.

1. A network model of thalamocortical (TC) and thalamic reticular (RE) neurons was developed based on electrophysiological measurements in ferret thalamic slices. Single-compartment TC and RE cells included voltage- and calcium-sensitive currents described by Hodgkin-Huxley type of kinetics. Synaptic currents were modeled by kinetic models of alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA), gamma-aminobutyric acid-A (GABAA) and GABAB receptors. 2. The model reproduced successfully the characteristics of spindle and slow bicuculline-induced oscillations observed in vitro. The characteristics of these two types of oscillations depended on both the intrinsic properties of TC and RE cells and their pattern of interconnectivity. 3. The oscillations were organized by the reciprocal recruitment between TC and RE cells, due to their manual connectivity and bursting properties. TC cells elicited AMPA-mediated excitatory postsynaptic potentials (EPSPs) in RE cells, whereas RE cells elicited a mixture of GABAA and GABAB inhibitory postsynaptic potentials (IPSPs) in TC cells. Because of the presence of a T current, sufficiently strong EPSPs could elicit a burst in RE cells, and TC cells could generate a rebound burst following GABAergic IPSPs. Under these conditions, interaction between the TC and RE cells produced sustained oscillations. 4. In the absence of spontaneous oscillation in any cell, the TC-RE network remained quiescent. Spindle oscillations with a frequency of 9-11 Hz could be initiated by stimulation of either TC or RE neurons. A few spontaneously oscillating TC neurons recruited the entire network model into a "waxing-and waning" oscillation. These "initiator" cells could be an extremely small proportion of TC cells. 5. In intracellular recordings, TC cells display a reduced ability for burst firing after a sequence of bursts. The "waning" phase of spindles was reproduced in the network model by assuming an activity-dependent upregulation of Ih operating via a calcium-binding protein in TC cells, as shown previously in a two-cell model. 6. Following the global suppression of GABAA inhibition, the disinhibited RE cells produced prolonged burst discharges that elicited strong GABAB-mediated currents in TC cells. The enhancement of slow IPSPs in TC cells was also due to cooperativity in the activation of GABAB-mediated current. These slow IPSPs recruited TC and RE cells into slower waxing-and-waning oscillations (3-4 HZ) that were even more highly synchronized. 7. Local axonal arborization of the TC to RE and RE to TC projections allowed oscillations to propagate through the network. An oscillation starting at a single focus induced a propagating wavefront as more cells were recruited progressively. The waning of the oscillation also propagated due to upregulation of Ih in TC cells, leading to waves of spindle activity as observed in experiments. 8. The spatiotemporal properties of propagating waves in the model were highly dependent on the intrinsic properties of TC cells. The spatial pattern of spiking activity was markedly different for spindles compared with bicuculline-induced oscillations and depended on the rebound burst behavior of TC cells. The upregulation of Ih produced a refractory period so that colliding spindle waves merged into a single oscillation and extinguished. Finally, reducing the Ih conductance led to sustained oscillations. 9. Two key properties of cells in the thalamic network may account for the initiation, propagation, and termination of spindle oscillations, the activity-dependent upregulation of Ih in TC cells, and the localized axonal projections between TC and RE cells. In addition, the model predicts that a nonlinear stimulus dependency of GABAB responses accounts for the genesis of prolonged synchronized discharges following block of GABAA receptors.

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PubMed1995

Synaptic and membrane mechanisms underlying synchronized oscillations in the ferret lateral geniculate nucleus in vitro.

1. The cellular basis for generation of spindle waves and a slower synchronized oscillation resembling absence seizures was investigated with extracellular and intracellular recording techniques in slices of ferret dorsal lateral geniculate nucleus (LGNd) maintained in vitro. 2. Intracellular recording from LGNd relay cells in vitro revealed that spindle waves occurred once every 3-30 s and were associated with barrages of inhibitory postsynaptic potentials (IPSPs) occurring at a frequency of 6-10 Hz. These IPSPs resulted in the generation of rebound low threshold Ca2+ spikes at 2-4 Hz, owing to the intrinsic propensity of LGNd relay cells to generate oscillatory burst firing in this frequency range. These rebound bursts of action potentials were highly synchronized with local multiunit and single unit activity. 3. The spindle wave-associated IPSPs in LGNd relay cells exhibited a mean reversal potential of -86 mV. This reversal potential was shifted to more depolarized membrane potentials with the intracellular injection of Cl- through the use of KCl-filled microelectrodes. Simultaneous recording from the perigeniculate nucleus (PGN) and LGNd revealed the IPSPs to be synchronous with the occurrence of burst firing in the PGN. Excitation of PGN neurons with local electrical stimulation after pharmacological block of excitatory amino acid transmission resulted in bicuculline-sensitive IPSPs in relay neurons similar in amplitude and time course to those occurring during spindle waves. 4. Application of (-)-bicuculline methiodide resulted in the abolition of spindle wave-associated IPSPs or in the slowing of the rate of rise, an increase in amplitude and a prolongation of these IPSPs; this resulted in a synchronized 2-4 Hz oscillation, in which each relay cell strongly burst on nearly every cycle, thus forming a paroxysmal event. Bath application of the GABAB receptor antagonist 2-OH-saclofen blocked these slowed oscillations, indicating that they are mediated by the activation of GABAB receptors. In contrast, pharmacological antagonism of GABAB receptors did not block the generation of normal spindle waves. 5. These and other results indicate that spindle waves are generated in the ferret LGNd in vitro as a network phenomenon occurring through an interaction between the relay cells of the LGNd and the GABAergic neurons of the PGN. We propose that burst firing in PGN cells hyperpolarizes relay neurons through activation of GABAA receptors. These IPSPs result in rebound burst firing in LGNd cells, which then excite PGN neurons.(ABSTRACT TRUNCATED AT 400 WORDS)

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PubMed1995

Role of the ferret perigeniculate nucleus in the generation of synchronized oscillations in vitro.

1. The cellular mechanisms by which neurons of the ferret perigeniculate nucleus (PGN) participate in the generation of spindle waves and slowed absence seizure-like oscillations were investigated with intracellular and extracellular recording techniques in geniculate slices maintained in vitro. 2. During spindle wave generation, PGN neurons generated repetitive (2-9 Hz) high frequency (up to 500 Hz) burst discharges mediated by the activation of a low threshold Ca2+ spike by the arrival of barrages of excitatory postsynaptic potentials (EPSPs). In most PGN cells at resting membrane potentials (-60 to -70 mV) spindle waves were associated with a progressive hyperpolarization that persisted as a prolonged after-hyperpolarization. 3. The EPSPs occurring in PGN cells were highly synchronized with burst firing in the neighbouring portion of the dorsal lateral geniculate nucleus (LGNd) and were intermixed with short duration inhibitory postsynaptic potentials (IPSPs). After block of GABAergic receptors, the EPSPs occurring during the generation of spindle waves reversed polarity at around 0 mV. In addition, these EPSPs were completely blocked with the bath application of the non-NMDA receptor antagonist 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX), as was spindle wave generation in both the PGN and LGNd. 4. Slowing the intraspindle frequency to 2-4 Hz with pharmacological block of GABAA receptors resulted in a marked increase in the intensity of burst firing by PGN cells such that the number of action potentials per burst increased from a maximum of thirteen to a maximum of sixty. Block of GABAA receptors also resulted in a marked increase in the amplitude and duration of the EPSP barrages arriving from the relay laminae during generation of the slowed oscillation. 5. These findings indicate that spindle waves are generated in the ferret LGNd in vitro through an interaction between the GABAergic neurons of the PGN and relay neurons, such that burst firing in relay neurons activates a barrage of EPSPs and a subsequent low threshold Ca2+ spike in PGN cells. This activation of PGN neurons inhibits a substantial number of relay cells, a few of which rebound burst after this IPSP, thus starting the cycle again. Block of GABAA receptors results in a marked enhancement of activity in PGN cells through increased excitation from relay cells and disinhibition from neighbouring PGN cells. This increased activity in PGN neurons results in a markedly enhanced activation of GABAB receptors in relay neurons and the subsequent generation of paroxysmal activity that is similar to that associated with absence seizures.

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PubMed1995

Spindle waves are propagating synchronized oscillations in the ferret LGNd in vitro.

1. The cellular features of propagation of spindle waves and a bicuculline-induced slow oscillation through sagittal slices of the ferret dorsal lateral geniculate nucleus (LGNd) maintained in vitro were examined with simultaneous extracellular and intracellular recordings from up to eight sites. Spindle waves typically propagated along the long axis (dorsal-ventral) of the sagittal slice at a speed of 0.3-1.5 mm/s and were synchronized along the line of projection between the perigeniculate nucleus (PGN) and the A, A1, and C laminae. 2. Spindle waves can be initiated with local electrical stimulation or can occur spontaneously in any part of the LGNd/PGN. On initiation of a spindle wave, spindle waves propagate away from the site of initiation. Spindle waves may propagate only locally or may collide with other spindle waves. Collision of spindle waves is associated with synchronization of the two network oscillations, and the spindle waves do not propagate past one another. 3. Repetitive electrical stimulation reveals that spindle wave generation and propagation exhibit a relative refractory period of between 7 and 14 s in vitro. Stimulation at rates of less than the refractory period results in the generation of abbreviated local spindle waves at the stimulation site, but not in the propagation of this spindle wave into adjacent regions of the slice. 4. Local block of non-N-methyl-D-aspartate (non-NMDA) excitatory amino acid receptors in the PGN with 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX) prevents the propagation of spindle waves across the point of application, indicating that the excitation of PGN neurons by thalamocortical cells is essential to the propagation of these oscillations. The local antagonism of non-NMDA receptors in the PGN results in the dorsal and ventral aspects of the LGNd slice behaving as independent spindle wave generators, even if before application of CNQX they were not. 5. Activation of a burst discharge in a single PGN neuron can result in the generation of a full spindle wave and the propagation of this spindle wave both dorsally and ventrally through the slice away from the activated PGN neuron. The ability of a burst of action potentials in a PGN neuron to generate a spindle wave is suppressed immediately after the generation of a spindle wave, but slowly returns over a 7- to 14-s period corresponding to the relative spindle wave refractory period.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

PubMed1994

Sensory gating mechanisms of the thalamus.

The thalamus is an obligatory station through which nearly all sensory information must pass before reaching the cerebral cortex. One of the major functions of the thalamus is the selective control of the flow of sensory-motor information to the cerebral cortex during different states of the sleep-wake cycle and arousal, and is controlled through the actions of various neurotransmitter systems in the brainstem, hypothalamus, and cerebral cortex. Recent investigations have detailed the cellular mechanisms, including the role of GABAA and GABAB receptors, involved in the generation of both normal (e.g. spindle waves) and abnormal (e.g. generalized seizures) patterns of activity in thalamocortical circuits. In addition, in vivo investigations have also revealed that the dense projection from the cerebral cortex to the thalamus may synchronize thalamocortical activity in a manner useful for sensory analysis. Together, these data suggest that oscillations and synchronization are important for both normal and abnormal function in thalamocortical circuits.

Animals↗

PubMed1994

Muscarinic modulation of a pattern-generating network: control of neuronal properties.

The aim of this article is to investigate the cellular mechanisms underlying cholinergic modulation of the pyloric network in the stomatogastric ganglion (STG) of the Cape lobster Jasus Ialandii. Bath application of the muscarinic agonists muscarine, oxotremorine, and pilocarpine on the STG activates a rhythmic pattern from a quiescent pyloric network. The mechanisms of this modulation were investigated on individual pyloric neurons isolated both from synaptic interactions within the network (by photoinactivation of most of the presynaptic neurons and pharmacological blockade of the remaining synapses) and from central inputs (by a sucrose block of the input nerve). All three muscarinic agonists activated bursting and plateau properties of all the neurons comprising the pyloric network. The activation was dose dependent, and was blocked by the muscarinic antagonists atropine, pirenzepine, and scopolamine. The oscillatory behavior triggered by the muscarinic stimulation was specific to each type of pyloric neuron. The isolated neuron AB had the shortest oscillation period and depolarizing phase. The constrictor neurons (LP, PY, IC) were the slowest oscillators, and only oscillated upon hyperpolarizing current injection. Under muscarinic modulation, the individual bursting activities of the isolated pyloric neurons were of the same type as their activities when isolated from the network but modulated by central inputs (Bal et al., 1988). The VD neuron is an exception since it was a rapid oscillator in the latter situation and became a slow oscillator when modulated by a single muscarinic agonist. To determine the relative importance of the muscarinic-dependent bursting properties of the individual pyloric neurons in the operation of the intact network, a progressive reconstruction of the synaptic circuitry was attempted. We found that under certain conditions of muscarinic modulation a new composite pacemaker could be created, composed of the electrically coupled VD, AB, and PD neurons. This can result in the generation of new pyloric patterns that were very sensitive to the membrane potential of individual network neurons. The data also confirmed that, in a rhythmic "pattern-generating network," the pacemaker role may not be definitely attributed to a given neuron but instead could be assigned to other neurons by modulation of their respective oscillatory capabilities.

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PubMed1993

Cellular mechanisms of a synchronized oscillation in the thalamus.

Spindle waves are a prototypical example of synchronized oscillations, a common feature of neuronal activity in thalamic and cortical systems in sleeping and waking animals. Spontaneous spindle waves recorded from slices of the ferret lateral geniculate nucleus were generated by rebound burst firing in relay cells. This rebound burst firing resulted from inhibitory postsynaptic potentials arriving from the perigeniculate nucleus, the cells of which were activated by burst firing in relay neurons. Reduction of gamma-aminobutyric acidA (GABAA) receptor-mediated inhibition markedly enhanced GABAB inhibitory postsynaptic potentials in relay cells and subsequently generated a slowed and rhythmic population activity resembling that which occurs during an absence seizure. Pharmacological block of GABAB receptors abolished this seizure-like activity but not normal spindle waves, suggesting that GABAB antagonists may be useful in the treatment of absence seizures.

Animals↗

PubMed1993

Mechanisms of oscillatory activity in guinea-pig nucleus reticularis thalami in vitro: a mammalian pacemaker.

1. The ionic mechanisms of rhythmic burst firing and single spike, tonic discharge were investigated with extracellular and intracellular recordings of single neurones in the guinea-pig nucleus reticularis thalami (NRT) maintained as a slice in vitro. 2. Activation of cortical/thalamic afferents to NRT neurones resulted in a short latency burst of action potentials which could be followed by a rhythmic sequence of oscillatory burst firing. Intracellularly, this oscillatory activity was associated with an alternating sequence of low threshold Ca2+ spikes separated by after-hyperpolarizing potentials. Intracellular injection of short duration hyperpolarizing current pulses resulted in a similar sequence of oscillatory burst firing, suggesting that this activity is an intrinsic property of NRT cells. The frequency of rhythmic burst firing was highly voltage and temperature dependent and was between 7-12 Hz at -65 to -60 mV at 38 degrees C. In addition, at depolarized membrane potentials, oscillatory burst firing was typically followed by a prolonged tail of single spike activity. 3. Application of the Na+ channel poison tetrodotoxin blocked the generation of fast action potentials, but left intact the rhythmic sequence of low threshold Ca2+ spikes separated by after-hyperpolarizing potentials (AHPs). The reversal potential of the AHPs was -94 mV, suggesting that it was mediated by an increase in K+ conductance. Extracellular application of tetraethylammonium or apamin, or intracellular injection of Cs+ or the Ca2+ chelating agent EGTA, blocked the Ca2+ spike AHP, indicating that it is mediated by a Ca(2+)-activated K+ current. 4. Block of the AHP resulted in the marked enhancement of a slow after-depolarizing potential (ADP). The slow ADP occurred only following the generation of low threshold Ca2+ spikes. Replacement of extracellular Ca2+ with Mg2+ or Sr2+ resulted in an abolition of the slow ADP. In addition, the increase in [Mg2+]o resulted in an abolition of the low threshold Ca2+ spike. In contrast, replacement of extracellular Ca2+ with Ba2+ did not abolish the slow ADP. These results indicate that the ADP can be activated by either Ca2+ or Ba2+, but not by Mg2+ or Sr2+. 5. Replacement of extracellular Na+ with choline+ did not abolish the slow ADP, while replacement with N-methyl-D-glucamine+ did, indicating that the slow ADP can be supported by choline+, but not by N-methyl-D-glucamine+. Neither chemical affected the low threshold Ca2+ spike. These results are consistent with the slow ADP being mediated by a Ca(2+)-activated non-selective cation (CAN) current.(ABSTRACT TRUNCATED AT 400 WORDS)

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