Membrane and synaptic properties of nucleus tractus solitarius neurons projecting to the caudal ventrolateral medulla

Projections from the nucleus of tractus solitarius (NTS) to the caudal ventrolateral medulla (CVLM) are important in mediating autonomic reflexes. However, little is known about the cellular properties of the CVLM-projecting NTS neurons. In this study, the CVLM-projecting NTS neurons were retrogradely labeled by fluorescent microspheres injected into the CVLM. Whole cell voltage- and current-clamp recordings were performed on labeled NTS neurons in coronal brainstem slices. Compared with unlabeled neurons, the labeled NTS neurons had more depolarized resting membrane potentials, larger input resistance, and higher firing activity in response to depolarizing currents. Bath application of an ionotropic glutamate receptor antagonist kynurenic acid and a non-NMDA receptor antagonist CNQX significantly decreased the firing activity in the majority of labeled NTS neurons. In contrast, an NMDA receptor antagonist AP5 failed to alter the firing activity in labeled neurons tested. While the glycine receptor antagonist strychnine had no effect on the firing activity, blockade of GABA(A)receptors with bicuculline significantly increased the firing rate in the majority of labeled NTS neurons. Furthermore, CNQX blocked the majority of spontaneous excitatory postsynaptic currents (EPSCs) and evoked EPSCs elicited by stimulation of the tractus solitarius. The residual spontaneous and evoked EPSCs were abolished by the nicotinic receptor antagonist mecamylamine and the purinergic P2X receptor antagonist iso-PPADS. Finally, while bicuculline completely blocked the miniature inhibitory postsynaptic currents (IPSCs), the spontaneous and evoked IPSCs were abolished by a combination of bicuculline and strychnine in labeled NTS neurons. Collectively, these data suggest that the CVLM-projecting neurons are a population of neurons with distinctive membrane properties.     

Red nucleus neurons actively contribute to the acquisition of classically conditioned eyelid responses in rabbits

The red nucleus (RN) is a midbrain premotor center that has been suggested as being involved in the acquisition and/or performance of classically conditioned nictitating membrane/eyelid responses. We recorded in rabbits the activity of RN and pararubral neurons during classical eyeblink conditioning using a delay paradigm. Neurons were identified by their antidromic activation from contralateral facial and accessory abducens nuclei and by their synaptic activation from the ipsilateral motor cortex (MC) and the contralateral cerebellar interpositus (IP) nucleus. For conditioning, we used a tone as a conditioned stimulus (CS) followed 250 ms later by a 100 ms air puff as an unconditioned stimulus (US) coterminating with it. Conditioned responses (CRs) were determined from the evoked changes in the electromyographic activity of the orbicularis oculi (OO) muscle. Recorded neurons were classified by their antidromic activation and by their changes in firing rate during the CS-US interval. Identified neurons increased their firing rates in relation to the successive conditioning sessions, but their discharge rates were related more to the EMG activity of the OO muscle than to the learning curves. Reversible inactivation of the IP nucleus with lidocaine during conditioning evoked a complete disappearance of both conditioned and unconditioned eyelid responses, and a progressive decrease in CR-related activity of RN neurons. In contrast, MC inactivation evoked a decrease in the acquisition process and an initial disfacilitation of neuronal firing (which was later recovered), together with the late appearance of CRs. Thus, RN neurons presented learning-dependent changes in activity following MC inactivation.     

Thalamic burst firing propensity: a comparison of the dorsal lateral geniculate and pulvinar nuclei in the tree shrew

Relay neurons in dorsal thalamic nuclei can fire high-frequency bursts of action potentials that ride the crest of voltage-dependent transient (T-type) calcium currents [low-threshold spike (LTS)]. To explore potential nucleus-specific burst features, we compared the membrane properties of dorsal lateral geniculate nucleus (dLGN) and pulvinar nucleus relay neurons using in vitro whole-cell recording in juvenile and adult tree shrew (Tupaia) tissue slices. We injected current ramps of variable slope into neurons that were sufficiently hyperpolarized to de-inactivate T-type calcium channels. In a small percentage of juvenile pulvinar and dLGN neurons, an LTS could not be evoked. In the remaining juvenile neurons and in all adult dLGN neurons, a single LTS could be evoked by current ramps. However, in the adult pulvinar, current ramps evoked multiple LTSs in >70% of recorded neurons. Using immunohistochemistry, Western blot techniques, unbiased stereology, and confocal and electron microscopy, we found that pulvinar neurons expressed more T-type calcium channels (Ca(v) 3.2) and more small conductance potassium channels (SK2) than dLGN neurons and that the pulvinar nucleus contained a higher glia-to-neuron ratio than the dLGN. Hodgkin-Huxley-type compartmental models revealed that the distinct firing modes could be replicated by manipulating T-type calcium and SK2 channel density, distribution, and kinetics. The intrinsic properties of pulvinar neurons that promote burst firing in the adult may be relevant to the treatment of conditions that involve the adult onset of aberrant thalamocortical interactions.     

Inhibition of GABAergic neurotransmission in the ventral tegmental area by cannabinoids

It was shown recently that Delta9-tetrahydrocannabinol, like several other drugs eliciting euphoria, stimulates dopaminergic neurons projecting from the ventral tegmental area (VTA) to the nucleus accumbens. The aim of the present work was to clarify the mechanism of this stimulatory effect. Our hypothesis was that cannabinoids depress the GABAergic inhibition of dopaminergic neurons in the VTA. Electrophysiological properties of VTA neurons in rat coronal midbrain slices were studied with the patch-clamp technique. GABA(A) receptor-mediated inhibitory postsynaptic currents (IPSCs) were evoked by electrical stimulation in the vicinity of the recorded neurons. The amplitude of IPSCs was depressed by the synthetic mixed CB1/CB2 cannabinoid receptor agonist WIN55212-2 (10(-6) and 10(-5) m). The CB1 cannabinoid receptor antagonist SR141716A (10(-6) m) prevented the inhibition produced by WIN55212-2 (10(-5) m). Two observations showed that IPSCs were depressed with a presynaptic mechanism. WIN55212-2 (10(-5) m) did not change the amplitude of miniature IPSCs recorded in the presence of tetrodotoxin. Currents evoked by pressure ejection of muscimol from a pipette were also not changed by WIN55212-2 (10(-5) m). The results indicate that activation of CB1 cannabinoid receptors inhibits GABAergic neurotransmission in the VTA with a presynaptic mechanism. Depression of the GABAergic inhibitory input of dopaminergic neurons would increase their firing rate in vivo. Accordingly, dopamine release in the projection region of VTA neurons, the nucleus accumbens, would also increase.     

Pharmacology of the brachium conjunctivum: red nucleus synaptic system in the baboon.

Acetylcholine, biogenic amines, and certain amino acids were applied by microiontophoresis to parvicellular and magnocellular red nucleus (RN) neurons of baboon while recording brachium conjunctivum (BC)-evoked and amino acid-evoked unit discharge from these neurons. Glycine, gamma-aminobutyric acid, and beta-alanine were potent depressants of BC-RN synaptic transmission, amino acid-evoked firing, and spontaneous activity of all RN neurons studied. Glycine was clearly more potent than the other 2 depressant amino acids. L-Glutamic and DL-homocysteic acid were strong excitants of all RN neurons tested. Dopamine, noradrenaline, and 5-hydroxytryptamine depressed the excitability of both parvicellular and magnocellular RN neurons; no excitatory effects were observed with these biogenic amines on RN neurons. Acetylcholine increased the rate of firing of spontaneously discharging parvicellular RN neurons and facilitated the amino acid-induced firing of these same neurons. Acetylcholine did not facilitate BC-RN synaptic transmission nor could this transmission be blocked by cholinergic antagonists. Unlike parvicellular RN neurons, the responsiveness of magnocellular neurons was either unaltered by acetylcholine or slightly decreased. These experiments demonstrate a difference in the pharmacologic responsiveness of parvicellular and magnocellular RN neurons to acetylcholine but do not provide evidence for a cholinergic input to RN via the brachium conjunctivum.     

Vasopressin-sensitive neurons in the lateral paraventricular nucleus area in a guinea pig slice preparation

The effects of vasopressin (VP) on hypothalamic neurons located in the region of the paraventricular nucleus (PVN) were analyzed using intracellular techniques in slices of guinea pig brains. Two different classes of neurons were electrophysiologically identified in the magnocellular lateral part of the PVN and in the adjacent area. In the former area, vasopressinergic neurons were identified according to their phasic activity and their endogenous properties. These neurons were not responsive to VP, applied through the perfusion medium or locally by pressure. On the other hand, nonmagnocellular neurons exhibiting low-threshold Ca2+ spikes (LTS) were recorded in the area adjacent to the lateral part of the PVN. LTS were deinactivated at hyperpolarized membrane levels and induced short bursts of action potentials. On these neurons, VP evoked depolarizations accompanied by increases in firing, without modification of membrane resistance. VP effects were not blocked by TTX, suggesting a postsynaptic action of the peptide. These data indicate that VP controls the firing pattern of LTS neurons and suggest that this action may involve collaterals of axons originating from neighbouring vasopressinergic neurons.     

Membrane Currents Influencing Action Potential Latency in Granule Neurons of the Rat Cochlear Nucleus

Granule cells are the most numerous neurons in the cochlear nucleus, but, because of their small size, little information on their membrane properties and ionic currents is available. We used an in vitro slice preparation of the rat ventral cochlear nucleus to make whole-cell recordings from these cells. Under current clamp, some granule neurons fired spontaneous action potentials and all generated a train of action potentials on depolarization (threshold current, 10–35 pA). Hyperpolarization increased the latency to the first action potential evoked during a subsequent depolarization. We examined which voltage-gated currents might underlie this latency shift. In addition to a fast inward Na⁺ current, depolarization activated two outward potassium currents. A transient current was rapidly inactivated by membrane potentials positive to -60 mV, while a second, more slowly inactivating current was observed following the decay of the transient current. No hyperpolarization-activated conductances were observed in these cells. Modelling of the currents suggests that removal of inactivation on hyperpolarization accounts for the increased action potential latency in granule cells. Such a mechanism could account for the 'pauser'-type firing patterns of the fusiform cells which receive a prominent projection from the granule cells in the dorsal cochlear nucleus.     

Electrophysiological analysis of suprachiasmatic nucleus projections to the ventrolateral preoptic area in the rat

The circadian pacemaker housed in the suprachiasmatic nucleus (SCN) synchronizes daily sleep-wake cycles, presumably by modulating the sleep-wake regulatory system, including ventrolateral preoptic area (VLPO) neurons. We used whole-cell patch-clamp recording to study the projections from the SCN to the VLPO in horizontal slices of rat hypothalamus. Single-pulse stimulation of the SCN region elicited postsynaptic currents (PSCs) in 20 of 66 neurons (30%) recorded within the VLPO region as verified by intracellular biocytin labelling. At a holding potential of -60 mV, the evoked PSCs had an amplitude of 17.6 +/- 3.2 pA (SEM) and a latency of 6.3 +/- 0.5 ms (n = 10). There was a trend for simple excitatory postsynaptic currents (EPSCs) to be evoked in the VLPO cluster, simple inhibitory postsynaptic currents (IPSCs) in the extended VLPO, and a combination of EPSCs and IPSCs in both regions. IPSCs were blocked reversibly by bicuculline (10 microm, n = 11). In both the presence and absence of bicuculline, EPSCs had fast and slow components that were blocked by 6,7-dinitroquinoxaline-2,3-dione (DNQX; 10 microm; n = 7), and (+/-)3-(2-carboxypiperazin-4-yl)-propyl-1-phosphonic acid (CPP; 10 microm, n = 6), respectively. Reversal potentials for the evoked IPSCs and EPSCs were consistent with mediation via GABAA and ionotropic glutamate receptors, respectively. These results suggest that the SCN region provides both inhibitory and excitatory inputs to single VLPO neurons, which are mediated, respectively, by GABAA receptors and by both non-NMDA and NMDA glutamate receptors. These projections may play important roles in conveying circadian input to systems in the preoptic area that regulate sleep and waking.     

Intracellular study of rat globus pallidus neurons: membrane properties and responses to neostriatal, subthalamic and nigral stimulation.

Physiological properties of globus pallidus (GP) neurons were studied intracellularly in anesthetized rats. More than 70% of the neurons exhibited continuous repetitive firing of 2-40 Hz, while others exhibited periodic burst firing or no firing. The repetitively firing neurons exhibited the following properties: spike accommodation; spike frequency adaptation; continuous firing with a frequency of about 100 Hz generated by intracellular current injections; fast anomalous rectification; ramp-shaped depolarization upon injection of depolarizing current; and post-active hyperpolarization. The burst firing neurons evoked a large depolarization with multiple spikes in response to depolarizing current, and a similar response was observed after the termination of hyperpolarizing current. The few neurons which did not fire spontaneous spikes exhibited strong spike accommodation when they were stimulated by current injections. The continuously firing neurons were antidromically activated by stimulation of the neostriatum (Str) (23 of 68), the subthalamic nucleus (STh) (55 of 75), and the substantia nigra (SN) (25 of 46). The antidromic latencies of the 3 stimulus sites were very similar (about 1 ms). None of the burst firing neurons were antidromically activated. Three non-firing neurons evoked antidromic responses only after Str stimulation. Only repetitively firing neurons evoked postsynaptic responses following stimulation of the Str and the STh. Stimulation of the Str evoked initial small EPSPs with latencies of 2-4 ms and strong, short duration IPSPs with latencies of 2-12 ms. Stimulation of the STh evoked short latency EPSPs overlapped with IPSPs. Frequently, these responses induced by Str and STh stimulation were followed by other EPSPs lasting 50-100 ms. These results indicated: (1) that the GP contains at least 3 electrophysiologically different types of neurons; (2) that GP projections to the Str, the STh, and the SN are of short latency pathways; (3) that Str stimulation evokes short latency EPSPs followed by IPSPs and late EPSPs in GP neurons; and (4) that STh stimulation evokes short latency EPSPs overlapped with short latency IPSPs and late EPSPs in GP neurons.     

Excitatory and inhibitory postsynaptic currents of the superior salivatory nucleus innervating the salivary glands and tongue in the rat

The excitatory and inhibitory synaptic inputs to parasympathetic preganglionic neurons in the superior salivatory (SS) nucleus were investigated in brain slices of neonatal (4-8 days old) rat using the whole-cell patch-clamp technique. The SS neurons innervating the submandibular and sublingual salivary glands and innervating the lingual artery in the anterior region of the tongue were identified by retrograde transport of a fluorescent tracer. Whole-cell currents were evoked by electrical stimulation of tissue surrounding the cell. These evoked postsynaptic currents were completely abolished by antagonists for N-methyl-D-aspartate (NMDA) glutamate, non-NMDA glutamate, gamma-aminobutyric acid type A (GABAA), and glycine receptors, suggesting that SS neurons receive glutamatergic excitatory, and GABAergic and glycinergic inhibitory synaptic inputs. In SS neurons for the salivary glands, the ratio of the NMDA component to the total excitatory postsynaptic current (EPSC) was larger than that of the non-NMDA component. This profile was reversed in the SS neurons for the tongue. In SS neurons for the salivary glands, the ratio of the GABAA component to the total IPSC was larger than the ratio of the glycine component to total inhibitory postsynaptic current (IPSC). The decay time constants of the GABAA component were slower than those for glycine. These characteristics of the excitatory and inhibitory inputs may be involved in determining the firing properties of the SS neurons innervating the salivary glands and the tongue.     

Ketamine suppresses synchronized discharges in the disinhibited amygdala slice.

The effect of ketamine on the paroxysmal depolarizing shift (PDS) induced by bicuculline was studied in rat amygdala slices using intracellular recording techniques. Stimulation of the ventral endopyriform nucleus evoked an excitatory postsynaptic potential (EPSP). After exposure to bicuculline (20 microM), the same stimulus intensity evoked burst firing. Superfusion of ketamine reversibly reduced the duration of PDS. Pretreatment of amygdala slices with DL-2-amino-5-phosphonovaleate (DL-APV, 50 microM) occluded the effect of ketamine suggesting that ketamine shortened the burst duration via its blocking action on the NMDA receptors. In all neurons tested, a large depolarizing shift remained in the presence of ketamine. The ketamine-resistant component was blocked by 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX, 8 microM) indicating its mediation by the non-NMDA receptors.     

Fast oscillations trigger bursts of action potentials in neocortical neurons in vitro: a quasi-white-noise analysis study

PURPOSE: Recent evidence supports the importance of action potential bursts in physiological neural coding, as well as in pathological epileptogenesis. To better understand the temporal dynamics of neuronal input currents that trigger burst firing, we characterized spectral patterns of stimulation current that generate bursts of action potentials from regularly spiking neocortical neurons in vitro. METHODS: Sharp microelectrodes were used for intracellular recording and stimulation of cortical neurons in rat brain slices. Quasi-white-noise (0-2 kHz) and "chirp" sine wave currents of decreasing wavelength were applied to represent a broad spectrum of stimulation frequencies. Action potential-related averaging of the stimulation current variations preceding bursting was used to characterize stimulation current patterns more likely to result in a burst rather than a single-spike response. RESULTS: Bursts of action potentials were most reliably generated by a preceding series of > or = 2 positive current transients at 164+/-37 Hz of the quasi-white-noise, and to sine wave currents with frequencies greater than 90 Hz. The intraburst action potential rate was linearly related to the frequency of the input sine wave current. CONCLUSIONS: This study demonstrates that regularly spiking cortical neurons in vitro burst in response to fast oscillations of input currents. In the presence of positive cortical feedback loops, encoding input frequency in the intraburst action potential rate may be safer than producing a high-frequency regular output spike train. This leads to the experimentally testable and therapeutically important hypothesis that burst firing could be an antiepileptogenic and/or anti-ictogenic mechanism.     

Electrical properties and synaptic potentials of rabbit pancreatic neurons

Pancreatic ganglia receive innervation from a wide variety of extrinsic nerves and supply the predominant innervation to pancreatic acini, islets, and ducts. This study used intracellular recordings to investigate the electrical properties and synaptic potentials of rabbit pancreatic neurons. Neurons had a mean resting membrane potential of -54+/-0.4 mV and generated action potentials with a mean overshoot of 10+/-0.4 mV and a mean after-spike hyperpolarization (ASH) of 11+/-0.5 mV with duration of 210+/-19 ms. Action potentials exhibited a high threshold (-15+/-1 mV) for intracellular stimulation and a phasic firing pattern was observed in response to prolonged depolarizing currents. Stimulation of attached nerve bundles evoked multiple fast excitatory postsynaptic potentials (fEPSPs) which were abolished by hexamethonium in 75% of neurons, while a non-cholinergic fEPSP was observed in 25% of the neurons. Repetitive stimulation (3-30 Hz) evoked muscarinic slow EPSPs with a mean amplitude of 8+/-2 mV and duration of 5+/-1 s in a small subset (21%) of neurons. Exogenous muscarine evoked a mean slow depolarization of 10+/-1 mV amplitude in 22% of neurons tested. Following repetitive nerve stimulation non-cholinergic late, slow EPSPs with a mean amplitude of 4.3+/-0.4 mV were recorded in 32% of neurons. Nicotinic transmission was subject to inhibition mediated by presynaptic muscarinic receptors at low (0.5 Hz) stimulus frequencies in 80% of neurons. At higher frequencies (> or =1 Hz), either facilitation or depression of nicotinic transmission was observed depending on the ganglion studied. A population (9%) of neurons exhibited spontaneous, low-amplitude pacemaker-like potentials. Spontaneous fEPSPs and action potentials were also observed and these occasionally occurred in rhythmically timed bursts. Thus, distinct subpopulations of pancreatic neurons could be identified on the basis of both their intrinsic electrical properties and the receptors mediating and/or modulating synaptic transmission. These neurons function as critical sites of integration for synaptic input from extrinsic pancreatic nerves and thereby determine the postganglionic firing patterns presented to the pancreatic exocrine and endocrine secretory cells.     

Influences of locus ceruleus, raphe dorsalis, and periaqueductal gray matter on somatosensory-recipient thalamic nuclei

Spontaneous and evoked discharge of neurons in the nucleus ventralis posterolateralis (VPL) and spontaneous discharge of neurons in the posterior group and nucleus lateralis posterior (LP) were conditioned by brief trains of stimuli to the locus ceruleus (LC), raphe dorsalis (RD), and periaqueductal gray matter (PAG) in cats anesthetized with pentobarbital or ketamine. Stimulation of LC and RD was without effect on VPL neurons, but induced a long-latency, long-lasting inhibition of LP neurons. Stimulation of the PAG induced marked inhibition of the firing of neurons in all three thalamic nuclei. No differences were found between cats anesthetized with ketamine or pentobarbital.     

Modulatory influences of red nucleus stimulation on the somatosensory responses of cat trigeminal subnucleus oralis neurons

Little is known of the effect of red nucleus (RN) stimulation on somatosensory neurons despite its known anatomic projections to somatosensory relay nuclei. The effect of RN stimulation on the somatosensory responses of trigeminal subnucleus oralis (Vo) neurons was investigated in chloralose- or barbiturate-anesthetized cats. Arrays of bipolar stimulating electrodes were inserted into the contralateral and ipsilateral RN and the contralateral thalamus. Extracellular single-unit recordings were obtained in Vo with tungsten microelectrodes. Neurons in Vo were excited to just suprathreshold by electrical stimulation within their receptive fields. Red nucleus influences were studied by applying 100-ms, 500-Hz conditioning trains to the contralateral or ipsilateral RN 130 ms prior to the peripheral test stimulus. The effect of RN stimulation was also tested on mechanically evoked responses of Vo cells. The somatosensory responses of most cells (70/73) were inhibited after RN stimulation. Some of these cells (15/70) could be antidromically activated from the contralateral thalamus. Stimulation of the RN resulted in excitation followed by inhibition in nine Vo cells. The results suggest that the RN may modulate transmission of somatosensory information through Vo.     

17beta-estradiol attenuates excitatory neurotransmission and enhances the excitability of rat parabrachial neurons in vitro

The steroid hormone 17beta-estradiol and its respective receptors have been found in several cardiovascular nuclei in the central nervous system including the parabrachial nucleus. In a previous study, we provided evidence that 17beta-estradiol attenuated an outward potassium conductance in parabrachial neurons of male rats, using an in vitro slice preparation. In this study we sought to enhance the comprehensive information provided previously on estradiol's postsynaptic effects in the parabrachial nucleus by directly examining whether 17beta-estradiol application will modulate excitatory synaptic neurotransmission. Using a pontine slice preparation and whole-cell patch-clamp recording, bath application of either 17beta-estradiol (20-100 muM) or BSA-17beta-estradiol (50 muM) decreased the amplitude of evoked excitatory postsynaptic currents (from 30-60% of control) recorded from neurons in the parabrachial nucleus. The paired pulse ratio was not significantly affected and suggests a post-synaptic site of action. The inhibitory effect on the synaptic current was relatively long-lasting (non-reversible) and was blocked by the selective estrogen receptor antagonist, ICI 182,780. Furthermore, 17beta-estradiol reduced the maximum current elicited by a ramp protocol, increased the input resistance measured between resting membrane potential and action potential threshold and caused an increase in the firing frequency of the cells under current-clamp. In summary, 17beta-estradiol caused 3 effects: first, a depolarization; second, a reduction in evoked excitatory postsynaptic potentials; and third, an enhancement of action potential firing frequency in neurons of the parabrachial nucleus. These observations are consistent with our previous findings and support a role for estrogen in modulating neurotransmission in this nucleus.     

Gamma-aminobutyric acid(B) receptor activation suppresses stimulus-evoked burst firing in rat substantia nigra reticulata neurons

Previous whole-cell patch-pipette studies showed that focal electrical stimulation of the subthalamic nucleus (STN) evokes a long-lasting complex excitatory postsynaptic currents (EPSC) and synaptically evoked bursts of action potentials in substantia nigra pars reticulata (SNR) neurons. Although synaptically evoked bursting may play a role in normal physiology, excessive burst firing correlates with symptoms of Parkinson's disease. We used patch-pipette recordings in rat brain slices to study the effects of baclofen on complex EPSCs and STN-induced burst firing in SNR neurons. Baclofen (1 μM) caused a reversible, 73% reduction in complex EPSCs, and this effect was blocked by the γ-aminobutyric acid(B) antagonist CGP35348 (100 μM). Using the loose-patch method to record extracellular potentials, a lower concentration of baclofen (100 nM) inhibited STN-evoked bursts, while leaving spontaneous firing of action potentials less affected. We suggest that strategies that selectively inhibit burst firing in the SNR might have therapeutic potential in the treatment of Parkinson's disease.     

Effect of labyrinthectomy on the spike generator of vestibular neurons in the guinea pig

In the guinea pig, in the absence of any stimulation, all the neurons of the vestibular nuclei are tonically firing. After an ipsilateral labyrinthectomy, these neurons first cease to fire but recover their previous discharge in 7 days. Here, we tested whether a modification of the spike generator, the process transforming synaptic currents into spike patterns, could be a factor underlying this restoration. For this purpose, we studied the firing rate responses of neurons of the medial vestibular nucleus in brain stem slices to intracellularly injected currents. We conclude that although labyrinthectomy induces some plastic changes in the excitability of the neurons of the medial vestibular nucleus, these changes do not underlie the restoration of activity which occurs in these neurons when they are deprived of their labyrinthine input.     

Blockade of inhibitory neurotransmission evoked seizure-like firing of cardiac parasympathetic neurons in brainstem slices of newborn rats: Implications for sudden deaths in patients of epilepsy

In patients of epilepsy a proportion of unexplained sudden deaths had been attributed to neurogenic arrhythmias. Although some evidence has suggested that epileptogenic activation of the cardiac parasympathetic nerves, which is revealed by ictal bradyarrhythmias or cardiac asystole, might be very critical in causing sudden deaths of patients of epilepsy the firing behavior of cardiac parasympathetic neurons (CPNs) during epileptic attack is not known. In the present study fluorescent tracer was injected into the cardiac sac of newborn rats to retrogradely label the parasympathetic neurons in the nucleus ambiguus (NA). The fluorescence-labeled NA neurons were further examined using whole-cell patch-clamp method in medulla slices with respiratory-like rhythm, and those with an inspiratory-related increase of the mixed inhibitory synaptic activity were identified as CPNs. We have demonstrated that blockade of the GABAergic and the glycinergic receptors in medulla slices evoked intermittent seizure-like firing of CPNs under current-clamp configuration, and evoked intermittent excitatory inward currents (IEICs) under voltage-clamp configuration. These results have given new evidence that CPNs might fire in a seizure-like pattern during epileptic attack, which might be responsible for the neurogenic ictal bradyarrhythmias, cardiac asystole, or even the sudden deaths of patients of epilepsy.     

Dendritic electrogenesis in rat hippocampal CA1 pyramidal neurons: functional aspects of Na+ and Ca2+ currents in apical dendrites

The regenerative properties of CA1 pyramidal neurons were studied through differential polarization with external electrical fields. Recordings were obtained from somata and apical dendrites in the presence of 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX), DL-2-amino-5-phosphonovaleric acid (APV), and bicuculline. S+ fields hyperpolarized the distal apical dendrites and depolarized the rest of the cell, whereas S÷ fields reversed the polarization. During intradendritic recordings, S+ fields evoked either fast spikes or compound spiking. The threshold response consisted of a low-amplitude fast spike and a slow depolarizing potential. At higher field intensities the slow depolarizing potential increased in amplitude, and additional spikes of high amplitude appeared. During intrasomatic recordings, S+ field evoked repetitive firing of fast spikes, whereas S÷ fields evoked a slow depolarizing, potential on top of which high- and low-amplitude spikes were evoked. Tetrodotoxin (TTX) blocked all types of responses in both dendrites and somata. Perfusion with Ca²⁺-free, Co²⁺-containing medium increased the frequency and amplitude of fast spikes evoked by S+ field and substantially reduced the slow depolarizing potential evoked by S÷ fields. Antidromic stimulation revealed that an all-or-none dendritic component was activated in the distal apical dendrites by back-propagating somatic spikes. The dendritic component had an absolute refractory period of about 4 ms and a relative refractory period of 10–12 ms. Ca²⁺-dependent spikes in the dendrites were followed by a long-lasting afterhyperpolarization (AHP) and a decrease in membrane input resistance, during which dendritic excitability was selectively reduced. The data suggest that generation of fast Na⁺ currents and slow Ca²⁺ currents in the distal part of apical dendrites is highly sensitive to the dynamic state of the dendritic membrane. Depending on the mode and frequency of activation these currents can exert a substantial influence on the input-output behavior of the pyramidal neurons. © 1996 Wiley-Liss, Inc.