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Multi-phase expiratory inhibition of phrenic motoneurons in the decerebrate cat.

We studied the membrane potential changes of 11 phrenic motoneurons (PMs), located in the C5 portion of the cervical spinal cord, in decerebrate, paralyzed and artificially ventilated cats. Intracellular chloride iontophoresis into PMs could reverse the waves of inhibitory postsynaptic potentials (IPSPs) causing membrane hyperpolarization during expiration. In all PMs, we revealed, in addition to the previously described late expiratory augmenting wave of IPSPs, an early expiratory decrementing wave of IPSPs. Moreover, in three PMs, recorded in two cats exhibiting slow respiratory rhythms, an additional wave of IPSPs was interposed between the early and late ones. The possible origins and roles of these three different waves of inhibition are discussed.

Animals↗

Electrophysiological characteristics of submucosal neurones in the proximal colon of guinea-pigs: comparisons with caecum and descending colon.

A systematic examination has been made of the active and passive electrophysiological properties and synaptic inputs of forty-four randomly impaled submucosal neurones in the proximal colon of the guinea-pig to compare these characteristics directly with those of submucosal neurones in the caecum (n = 70) and descending colon (n = 45). Within each of the three electrophysiological classes of submucosal neurones identified (S, S/AH and AH), no statistically significant regional differences were found with respect to the resting membrane potential, membrane time constant or input resistance between neurones of the proximal colon, descending colon and caecum. Of submucosal neurones from the proximal colon, forty-three of forty-four (98%) received fast excitatory synaptic potentials (fast EPSPs); thirty-nine (91%) were S neurones and the others were S/AH neurones; only one of the forty-four cells (2%) was an AH neurone. An idazoxan-sensitive slow inhibitory postsynaptic potential (slow IPSP) was induced in thirty of forty-three S and S/AH neurones (70%) of the proximal colon, compared with sixty-one of sixty-six caecal neurones (92%) and twelve of forty-one neurones (29%) in the descending colon. The mean (+/- S.E.M.) amplitude of the slow IPSP in proximal colonic neurones was 17 +/- 1 mV (range, 6-30 mV; n = 30), compared with the significantly larger synaptic response (25 +/- 1 mV; range, 7-38 mV; n = 66; P < 0.05) recorded in the caecum; the mean slow IPSP amplitude in the descending colon was significantly smaller (12 +/- 2 mV; range, 5-27 mV; n = 12; P < 0.05) than that in the caecum. In the proximal colon and caecum, only those neurones with a slow IPSP had a hyperpolarizing response to noradrenaline, whereas about 50% of those neurons of the descending colon that lacked a slow IPSP were hyperpolarized by noradrenaline, acting via alpha 2-adrenoceptors. Thus, the electrophysiological characteristics of the submucosal neurones of the proximal colon more closely resemble those of the caecum than those of the descending colon, of which many do not have a functional noradrenergic synaptic input. Furthermore, the results confirm that there are fundamental regional differences in the guinea-pig large intestine with respect to the synaptic organization of submucosal neurones of particular electrophysiological classes.

Adrenergic alpha-Agonists↗

Organization of synaptic inputs to paracerebral feeding command interneurons of Pleurobranchaea californica. III. Modifications induced by experience.

Phasic paracerebral feeding command interneurons (PCP's) were studied in whole-animal preparations of Pleurobranchaea drawn from four populations with different behavioral histories: food avoidance conditioned, yoked controls, food satiated, and naive. PCP responses to chemosensory food stimuli (liquefied squid) and mechanosensory touch stimuli (tactile stimulation of anterior and posterior structures) were recorded intracellularly, scored blind, and compared quantitatively across the four populations. PCP's from avoidance-conditioned specimens (10, 18, 19) showed decreased excitatory and increased inhibitory responses to food and touch in comparison with naive (untrained) specimens. Control animals did not show these effects. PCP's from satiated specimens showed decreased excitatory and increased inhibitory responses to food and touch in comparison with PCP's from control, naive, and conditioned specimens. Inhibitory postsynaptic potentials (IPSPs) induced in PCP's of conditioned and satiated specimens by food and touch are indistinguishable in amplitude and waveform from IPSPs produced in the same PCP's by the previously described cyclic inhibitory network (CIN; Ref. 13). In addition, tonic paracerebral neurons (PCT's) that lack input from the CIN, are not inhibited but rather are excited in trained and satiated animals. Therefore the inhibitory responses to food and touch by PCP's of conditioned and satiated specimens appear to be mediated by the CIN. This study demonstrates that associative and nonassociative processes (learning and food satiation, respectively) manifest similarly at the level of command interneurons. The findings furnish a neurophysiological explanation for behavioral motivation in Pleurobranchaea, namely, modulation of the balance of excitation/inhibition in command neurons controlling the corresponding behavior. A cellular model of food avoidance learning and food satiation is formulated to account for these data, based on the identified neural circuitry of the paracerebral command system (15, 17).

Animals↗

Intracellular records of the effects of primary afferent input in lumbar spinoreticular tract neurons in the cat.

1. The afferent-evoked synaptic input to lumbar spinal cord (L5-S1) neurons that were activated antidromically from the medial pontomedullary reticular formation (nucleus reticularis gigantocelluaris and vicinity) was investigated with the use of intracellular recordings in pentobarbital sodium-anesthetized cats. 2. Spinoreticular tract (SRT) neurons (n = 33) were categorized into three types ("deep-inhibited," "deep-complex," and "intermediate") on the basis of their locations and of their responses to natural and electrical stimulation. 3. The deep-inhibited-type neurons, located in the medial part of the deeper laminae (approximately VI-VIII), comprised a large component of the sample (20/33). They had no demonstrable excitatory receptive field (RF). However, electrical stimulation of low-threshold cutaneous afferents of hindlimb nerves evoked inhibitory postsynaptic potentials (IPSPs) via an oligosynaptic linkage. High-threshold cutaneous and muscle afferents also evoked IPSPs. 4. In the deep-complex-type neurons (8/33), electrical stimulation of low-threshold cutaneous afferents evoked complex IPSP-excitatory postsynaptic potential (EPSP) sequences. With intense stimuli, long-latency C-fiber-like EPSPs were evoked. Two of these eight neurons were characterized as wide-dynamic-range (WDR) neurons with large, excitatory and inhibitory cutaneous RFs. 5. Intermediate-type neurons (5/33) were concentrated in the lateral spinal gray and relatively superficially (approximately lamina V). These neurons had convergent low- and high-threshold cutaneous inputs (WDR neurons). Electrical stimulation of low-threshold cutaneous afferent fibers from within the excitatory RF evoked mono- or disynaptic EPSPs followed by IPSPs. High-threshold muscle and cutaneous afferents also evoked EPSPs. 6. These results show that SRT neurons have a variety of response characteristics resulting from various degrees of spatial and temporal summation of primary afferent input. Neurons with widespread inhibitory responses but no excitatory drive from the periphery comprise a surprisingly large component of the SRT: the function of these cells is unknown. It is apparent that the spinoreticular projection has considerable functional heterogeneity.

Animals↗

Simulations of cortical pyramidal neurons synchronized by inhibitory interneurons.

1. The interaction between inhibitory interneurons and cortical pyramidal neurons was studied by use of computer simulations to test whether inhibitory interneurons could assist in phase-locking postsynaptic cells. Two models were used: a simplified model, which included only 3 membrane channels, and a detailed 11-channel model. 2. The 11-channel model included most of the ion channels known to be present in neocortical pyramidal neurons as well as calcium diffusion and other membrane mechanisms. The kinetics for the channels were obtained from voltage-clamp studies in a variety of preparations. The parameters were then adjusted to produce repetitive bursting similar to that seen in some cortical pyramidal cells entrained during visual stimulation. 3. Phase-locking to a train of inhibitory postsynaptic potentials (IPSPs) located on or near the soma was observed in the 3-channel model cell subjected to random synaptic bombardment. In the 11-channel model, phase-locking due to multiple IPSPs was compared with phase-locking due to multiple excitatory postsynaptic potentials (EPSPs). Phase-locking began to occur when 20% of the IPSPs (20/100) or 40% of the EPSPs (4,000/10,000) were synchronized. The exact percentages differed with different 11-channel models, but either EPSPs or IPSPs would generally produce entrainment with approximately 40% synchronization. Thus 40 inhibitory boutons had an effect equivalent to 4,000 excitatory boutons in producing phase-locking. 4. Phase-locking with IPSPs in these models was possible because the IPSPs could cause either an increase or a decrease in firing rate over a limited range. The IPSPs served a modulatory role, increasing the rate of firing in some cases and decreasing it in others, depending on the state of the cell. 5. We examined frequency entrainment by IPSPs. In the 3-channel model, frequency entrainment of a postsynaptic cell was observed with a rapid train of strong (20-100 nS), brief, compound IPSPs. A 40-Hz compound IPSP train of 60 nS entrained cells having initial firing rates between 32 and 47 Hz. Below this range, cells could be partially entrained. Above the range, entrainment would fail. Frequency entrainment in the 3-channel model generally occurred on the first cycle after onset of the IPSPs. 6. Phase-locking and frequency entrainment were less robust in the 11-channel model. This was partly because bursts rather than individual spikes were being entrained. A 40-Hz, 90-nS compound IPSP train entrained a model cell upward from 34 Hz. Downward frequency entrainment also occurred.(ABSTRACT TRUNCATED AT 400 WORDS)

Calcium Channels↗

Synchronized Ca2+ signals mediated by Ca2+ action potentials in the hippocampal neuron network in vitro.

Periodic, synchronized Ca2+ signals appeared 30-120 min after the application of tetrodotoxin, 4-aminopyridine and Cs+, and became stable in interval (6-47s) for hours. The Ca2+ signals were accompanied by excitatory or inhibitory postsynaptic potentials (excitatory postsynaptic currents (EPSCs) for the former) and blocked by the simultaneous application of 6-cyano-7-nitroquinoxaline-2,3-dione and 3-((RS)-2-carboxypiperazin-4-yl)-propyl-1-phosphonic acid or treatment with Ca2+ -free solution, nicardipine, or omega-conotoxin MVIIC (omegaCTX), but not with ryanodine, caffeine, thapsigargin or CPP alone. Nicardipine largely, but omegaCTX less, blocked Ca2+ action potentials or voltage pulse-induced Ca2+ currents at the cell soma, while omegaCTX completely blocked autaptic EPSCs. Ca2+ signals within a neuron occurred almost simultaneously in the cell soma and all the processes (> 200 microm), while the latency between Ca2+ signals of neighbouring neurons varied over hundreds of ms like that of Ca2 action potential induction from EPSPs. Ca2+ signals propagated in random directions throughout neural circuits. Thus, when Na+ and K+ channels are blocked, Ca2+ action potentials spontaneously occur somewhere in a neuron, eventually propagate via the cell soma to the presynaptic terminals and activate excitatory synaptic transmission, causing synchronized Ca2+ signals. The results further suggest that the axon of hippocampal neurones have the potential ability to convey coded information via Ca2+ action potentials.

4-Aminopyridine↗

The K+ channel opener diazoxide enhances glutamatergic currents and reduces GABAergic currents in hippocampal neurons.

1. The effect of diazoxide, an opener of ATP-sensitive K+ channels (KATP channels) has been investigated in the rat hippocampal slices by the use of extracellular and intracellular recording techniques. 2. In control solution, diazoxide enhanced the CA1 and CA3 field excitatory postsynaptic potentials (EPSPs) and produced interictal activities in CA3. These effects were neither prevented by KATP blockers, including glibenclamide (3-30 microM) or tolbutamide (500 microM), nor mimicked by another KATP opener such as galanine (1 microM); thus these effects are probably not mediated by KATP channels. 3. Using intracellular recording, we then studied, in CA3 pyramidal neurons, the effect of diazoxide on the EPSPs and the fast and slow inhibitory postsynaptic potentials (IPSPs). 4. In presence of bicuculline (10 microM) and phaclofen (50 microM), to block, respectively, fast and slow IPSPs, diazoxide reversibly enhanced the EPSPs. 5. In presence of 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX; 10 microM), to block EPSPs, diazoxide reversibly decreased both fast and slow IPSPs. 6. These effects of diazoxide on the EPSPs and fast and slow IPSPs were associated neither with a change of the reversal potential of the EPSPs or the fast and slow IPSPs nor with a change of the input resistance and membrane potential. 7. Using single electrode voltage-clamp technique, we then tested the effects of diazoxide on the currents generated by applications of glutamate or gamma-aminobutyric acid (GABA) -A and -B analogues. 8. In presence of tetrodotoxin (TTX; 1 microM), diazoxide reversibly enhanced the peak currents evoked by alpha-amino-3-hydroxy-5-methyl-4- isoxazolepropionate (AMPA; 3-5 microM), quisqualate (5-10 microM) and N-methyl-D-aspartate (NMDA; 10 microM), but not those evoked by kainate (1-3 microM). 9. In presence of TTX (1 microM), diazoxide reversibly decreased the GABA- (1-5 mM), isoguvacine- (30-60 microM), and baclofen- (10-30 microM) mediated peak currents. 10. It is concluded that, in the hippocampus, diazoxide enhances the excitatory glutamatergic currents and reduces the GABAergic inhibition, thus generating paroxystic activities. We suggest that these effects are mediated by second messenger cascades.

Adenosine Triphosphate↗

Monosynaptic connections between identified A and B photoreceptors and interneurons in Hermissenda: evidence for labeled-lines.

The cellular and synaptic organization of the eye of the nudibranch mollusk Hermissenda is well-documented. The five photoreceptors within each eye are mutally inhibitory and can be classified into two types: A and B based on electrophysiological and anatomical criteria. Two of the three type B and two type A photoreceptors can be further identified according to their medial or lateral positions within each eye. In addition to reciprocal synaptic connections between photoreceptors, photoreceptors also project to second-order neurons in the cerebropleural ganglion. The second-order neurons receive convergent synaptic input from two additional sensory pathways; however, it has not been previously established if lateral A, lateral B, or medial B photoreceptors converge onto the same second-order neurons. To determine the specific synaptic organization of these components of the visual system, we have examined monosynaptic connections between identified lateral and medial type A and B photoreceptors and second-order cerebropleural (CP) interneurons. We found that monosynaptic connections between identified lateral A and lateral and medial B photoreceptors and CP interneurons follow a labeled-line principle. Illumination of the eyes or extrinsic depolarizing current applied to identified photoreceptors evoked excitatory and inhibitory postsynaptic potentials (EPSPs and IPSPs, respectively) in different CP interneurons. The PSPs in CP interneurons followed one-for-one spikes in the photoreceptors and could be elicited in artificial seawater solutions containing high divalent cations. Identified photoreceptors projected to more than one CP interneuron and expressed both excitatory and inhibitory connections with the different CP interneurons. In examples where a monosynaptic connection between a lateral B photoreceptor and a CP interneuron was identified, lateral A, medial A, or medial B photoreceptors did not project to the same CP interneuron. Moreover, when connections between medial B and CP interneurons were identified, lateral A, medial A, and lateral B connections were not found to project to the same CP interneuron. Similar results were obtained for a lateral A and CP interneuron connection. These results indicate that divergent labeled-lines exist between specific photoreceptors and second-order CP interneurons and potential convergence of synaptic input from primary and secondary elements of the visual system must occur at sites that are postsynaptic to the CP interneurons.

Action Potentials↗

A role for GABAB receptors in excitation and inhibition of thalamocortical cells.

Gamma-aminobutyric acid (GABA) in the thalamus has mainly been associated with the inhibitory modulation of the sensory and cortical flow of information via a 'classical', chloride-dependent, GABAA receptor-mediated action. However, the discovery of a late, long-lasting potassium-dependent inhibitory postsynaptic potential (IPSP) mediated by GABAB receptors present on thalamocortical cells, has allowed new insights into our understanding of the physiological role of this neurotransmitter. In particular, work on the dorsal lateral geniculate nucleus indicates that together with a relatively weak inhibition, GABAB receptor-mediated IPSPs 'prepare' thalamocortical cells for burst firing by activating low-threshold calcium potentials. Thus, GABA in the thalamus can no longer be viewed only as a 'classical' inhibitory transmitter but also as a neuromodulator with a 'priming' role for burst firing excitation. This dual role of GABAB receptors in inhibition and excitation of thalamocortical cells might allow different interpretations of earlier findings in animals and humans, both in healthy and pathological conditions. It will also help to identify new functions for postsynaptic GABAB receptors in other parts of the central nervous system.

Animals↗

Decreased GABA and increased glutamate receptor-mediated activity on inferior colliculus neurons in vitro are associated with susceptibility to ethanol withdrawal seizures.

Cessation of ethanol administration in ethanol-dependent rats results in an ethanol withdrawal (ETX) syndrome, including audiogenic seizures (AGS). The inferior colliculus (IC) is the initiation site for AGS, and membrane properties of IC neurons exhibit hyperexcitability during ETX. Previous studies observed that ETX alters GABA and glutamate neurotransmission in certain brain sites. The present study evaluated synaptic properties and actions of GABA or glutamate antagonists during ETX in IC dorsal cortex (ICd) neurons in brain slices from rats treated with ethanol intragastrically 3 times daily for 4 days. A significant increase of spontaneous action potentials (APs) was observed during ETX. The width, area and rise time of excitatory postsynaptic potentials (EPSPs) evoked by stimulation in the commissure of IC were significantly elevated during ETX. A fast EPSP was sensitive to block by the non-NMDA receptor antagonist, 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX), and a slow EPSP was sensitive to the NMDA receptor antagonist, 2-amino-5-phosphonovalerate (AP5). However, during ETX the concentration of CNQX or AP5 needed to block these EPSPs was elevated significantly. Inhibitory postsynaptic potentials (IPSPs) in ICd neurons evoked in both normal and ETX rats were blocked by the GABA(A) antagonist, bicuculline. However, IPSPs during ETX displayed a significantly greater sensitivity to bicuculline. These data indicate that decreased GABA(A)-mediated inhibition and increased glutamate-mediated excitability in IC may both be critical mechanisms of AGS initiation during ETX, which is similar to observations in a genetic form of AGS. The common changes in IC neurotransmission in these AGS forms may be general mechanisms subserving AGS and other forms of auditory system pathophysiology in which the IC is implicated.

Acoustic Stimulation↗

On the role of muscarinic and peptidergic receptors in ganglionic transmission in bullfrogs in vivo.

Synaptic activity of individual B and C cells in the paravertebral sympathetic ganglia of urethan-anesthetized bullfrogs was monitored with intracellular electrodes. Postganglionic activity from the B and C fiber populations was monitored with suction electrodes. Intravenous infusion of muscarine (0.1 ml of 8 microM) excited individual B cells and increased the amplitude and rate of spontaneous, postganglionic B fiber population discharges. Muscarine also increased the number of action potentials (APs) within each burst of synaptic activity in individual C cells. Because atropine (0.1 ml of 0.1 microM) had little or no effect on postganglionic population B or C fiber activity, the muscarinic slow inhibitory postsynaptic potentials and slow excitatory postsynaptic potentials (EPSPs) are unlikely to be involved in the transmission, modulation, or integration of postganglionic outflow in vivo. Atropine did, however, decrease the number of APs per burst in individual C cells, an effect that could be explained if excitatory presynaptic muscarinic receptors exist on C fiber terminals. Stimulation of preganglionic C fibers at "physiological" frequencies evoked a lasting afterdischarge in postganglionic B fibers that was blocked by a combination of atropine and [D-pyro-Glu1,D-Phe2,D-Trp3,6]-luteinizing hormone-releasing hormone (LHRH). Release of LHRH from C fiber terminals and activation of the peptidergic, late-slow EPSP mechanism in B cells may therefore play a role in ganglionic transmission in vivo.

Action Potentials↗

Physiological properties of the Mauthner system in the adult zebrafish.

We investigated the morphological and electrophysiological properties of the Mauthner (M-) cell and its networks in the adult zebrafish (Danio rerio) in comparison with those in the goldfish (Carassius auratus). The zebrafish M-cell has an axon cap, a high resistivity structure which surrounds the initial segment of the M-axon, and accounts for an unusual amplification of the fields generated within and around it. Second, extra- and intracellular recordings were performed with microelectrodes. The resting potential was approximately -80 mV with an input resistance of approximately 0.42 M omega. The M-cell extracellular field was large (10-20 mV), close to the axon hillock, and the latency of antidromic spikes short (approximately 0.4 milliseconds), confirming a high conduction velocity in the M-axon. The extrinsic hyperpolarizing potential (EHP), which signals firing of presynaptic cells and collateral inhibition, was markedly lower at frequencies of spinal stimulation > approximately 5/second, suggesting an organization of the recurrent collateral network similar to that in the goldfish. Inhibitory postsynaptic potentials (IPSPs) were highly voltage-dependent; their decay time constant was increased by depolarizations. The presynaptic neurons which are numerous could be identified by their passive hyperpolarizing potential (PHP) produced by the M-spike current. Auditory responses, mediated via mixed synapses (electrical and chemical), had short delays and hence are well suited to trigger the escape reaction. The similarities of their properties indicate that the wealth of information generated over decades in the goldfish can be extrapolated to the zebrafish.

Animals↗

Two types of synaptic facilitation recorded in pyramidal cells of in vitro hippocampal slices from guinea pigs.

PyramidaL cells in CA1 hippocampus show two types of increase in the excitatory postsynaptic potential (EPSP) during paired pulse stimulation of the afferent fibres in stratum radiatum. For 15-300 ms interstimulus intervals, both the initial slope and the peak amplitude of the EPSP are increased, which is mainly due to an increased excitatory synaptic current. For 300 ms-2 s intervals, the predominant change is an increase in the peak amplitude. The latter type of facilitation is caused by a decrease in a superimposed inhibitory postsynaptic potential (IPSP).

Animals↗

Excitatory transmission in the basolateral amygdala.

1. Intracellular current-clamp recordings obtained from neurons of the basolateral nucleus of the amygdala (BLA) were used to characterize postsynaptic potentials elicited through stimulation of the stria terminalis (ST) or the lateral amygdala (LA). The contribution of glutamatergic receptor subtypes to excitatory postsynaptic potentials (EPSPs) were analyzed by the use of the non N-methyl-D-aspartate (non-NMDA) antagonist, 6-cyano-7-nitro-quinoxaline-2,3-dione (CNQX), and the NMDA antagonist, (DL)-2-amino-5-phosphonovaleric acid (APV). 2. Basic membrane properties of BLA neurons determined from membrane responses to transient current injection showed that at the mean resting membrane potential (RMP; -67.2 mV) the input resistance (RN) and time constant for membrane charging (tau) were near maximal, and that both values were reduced with membrane hyperpolarization, suggesting an intrinsic regulation of synaptic efficacy. 3. Responses to stimulation of the ST or LA consisted of an EPSP followed by either a fast inhibitory postsynaptic potential (f-IPSP) only, or by a fast- and subsequent slow-IPSP (s-IPSP). The EPSP was graded in nature, increasing in amplitude with increased stimulus intensity, and with membrane hyperpolarization after DC current injection. Spontaneous EPSPs were also observed either as discrete events or as EPSP/IPSP waveforms. 4. In physiological Mg2+ concentrations (1.2 mM), at the mean RMP, the EPSP consisted of dual, fast and slow, glutamatergic components. The fast-EPSP (f-EPSP) possessed characteristics of kainate/quisqualate receptor activation, namely, the EPSP increased in amplitude with membrane hyperpolarization, was insensitive to the NMDA receptor antagonist, APV (50 microM), and was blocked by the non-NMDA receptor antagonist, CNQX (10 microM). In contrast, the slow-EPSP (s-EPSP) decreased in amplitude with membrane hyperpolarization, was insensitive to CNQX (10 microM), and was blocked by APV (50 microM), indicating mediation by NMDA receptor activation. 5. In the presence of CNQX (10 microM), ST stimulation evoked an APV-sensitive s-EPSP. In contrast, LA stimulation evoked a f-IPSP, which when blocked by subsequent addition of bicuculline methiodide (BMI; 30 microM) revealed a temporally overlapping APV-sensitive s-EPSP. These data suggest that EPSP amplitude and duration are determined, in part, by the shunting of membrane conductance caused by a concomitant IPSP. 6. Superfusion of either CNQX or APV in BLA neurons caused membrane hyperpolarization and blockade of spontaneous EPSPs and IPSPs, suggesting that these compounds may act to block tonic excitatory amino acid (EAA) release within the nucleus, and that a degree of feed-forward inhibition occurs within the nucleus.(ABSTRACT TRUNCATED AT 400 WORDS)

2-Amino-5-phosphonovalerate↗

Excitatory amino acid-receptor-mediated EPSPs in rat dorsolateral septal nucleus neurones in vitro.

1. Intracellular recordings were made from rat dorsolateral septal nucleus (DLSN) neurones in vitro. We investigated depolarizations resulting from pressure application of excitatory amino acids and compared these to synaptically evoked excitatory postsynaptic potentials (EPSPs). 2. EPSPs evoked by focal fimbrial afferent stimulation in saline with 30-50 microM-bicuculline and 1.2 mM-Mg2+ yielded a linear amplitude-voltage relationship: their reversal potential was -3 mV. These EPSPs exhibited little sensitivity to 2-amino-5-phosphonopentanoate (APV), an N-methyl-D-aspartate(NMDA)-receptor-specific antagonist, but were markedly depressed by kynurenic acid, a broad-spectrum excitatory amino acid antagonist. 3. In Mg2(+)-free solution, the amplitude and the duration of EPSPs were increased markedly masking the following inhibitory postsynaptic potential (IPSP) and the late hyperpolarizing potential (LHP). These facilitated and broadened EPSPs were sensitive to APV or Mg2+. The APV or Mg2(+)-sensitive component of the EPSP obtained by digital subtraction suggests a slower time course for the NMDA-receptor-mediated EPSP compared to the non-NMDA-receptor-mediated EPSP. On the other hand, in normal Mg2+ solution an EPSP evoked by either a single strong stimulus or by repetitive stimuli had APV-sensitive components. 4. The depolarizing potentials induced by pressure application of glutamate, kainate, alpha-amino-3-hydroxy-5-methylisoxazole-4-propionate (AMPA), quisqualate or NMDA were compared. The amplitude-voltage relationship of depolarizations induced by NMDA obtained in a normal Mg2+ solution was non-linear, but approached linearity when the same responses were recorded in a Mg2(+)-free solution. Depolarizations induced by kainate, AMPA and quisqualate were linear in their amplitude-voltage relationship in the presence or absence of Mg2+. APV blocked NMDA-induced depolarizations specifically, while kynurenic acid blocked all the depolarizations induced by NMDA, quisqualate, or kainate. 5. Our data demonstrate the existence of NMDA-receptor-mediated synaptic potentials in the rat DLSN, the characteristics of which are similar to those in other central nervous system regions.

2-Amino-5-phosphonovalerate↗

Impact of temporal variation and the balance between excitation and inhibition on the output of the perfect integrate-and-fire model.

We consider how the output of the perfect integrate-and-fire (I&F) model of a single neuron is affected by the properties of the input, first of all by the distribution of afferent excitatory and inhibitory postsynaptic potential (EPSP, IPSP) inter-arrival times, discriminating particularly between short- and long-tailed forms, and by the degree of balance between excitation and inhibition (as measured by the ratio, r, between the numbers of inhibitory and excitatory inputs). We find that the coefficient of variation (CV; standard deviation divided by mean) of efferent interspike interval (ISI) is an increasing function of the length of the tail of the distribution of EPSP inter-arrival times and the ratio r. There is a range of values of r in which the CV of output ISIs is between 0.5 and 1. Too tight a balance between EPSPs and IPSPs will cause the model to produce a CV outside the interval considered to correspond to the physiological range. Going to the extreme, an exact balance between EPSPs and IPSPs as considered in [24] ensures a long-tailed ISI output distribution for which the moments such as mean and variance cannot be defined. In this case it is meaningless to consider quantities like output jitter, CV, etc. of the efferent ISIs. The longer the tail of the input inter-arrival time distribution, the less is the requirement for balance between EPSPs and IPSPs in order to evoke output spike trains with a CV between 0.5 and 1. For a given short-tailed input distribution, the range of values of r in which the CV of efferent ISIs is between 0.5 and 1 is almost completely inside the range in which output jitter (standard deviation of efferent ISI) is greater than input jitter. Only when the CV is smaller than 0.5 or the input distribution is a long-tailed one is output less than input jitter [21]. The I&F model tends to enlarge low input jitter and reduce high input jitter. We also provide a novel theoretical framework, based upon extreme value theory in statistics, for estimating output jitter, CV and mean firing time.

Action Potentials↗

The role of chloride transport in postsynaptic inhibition of hippocampal neurons.

Hippocampal inhibitory postsynaptic potentials are depolarizing in granule cells but hyperpolarizing in CA3 neurons because the reversal potentials and membrane potentials of these cells differ. Here the hippocampal slice preparation was used to investigate the role of chloride transport in these inhibitory responses. In both cell types, increasing the intracellular chloride concentration by injection shifted the reversal potential of these responses in a positive direction, and blocking the outward transport of chloride with furosemide slowed their recovery from the injection. In addition, hyperpolarizing and depolarizing inhibitory responses and the hyperpolarizing and depolarizing responses to the inhibitory neurotransmitter gamma-aminobutyric acid decreased in the presence of furosemide. These effects of furosemide suggest that the internal chloride activity of an individual hippocampal neuron is regulated by two transport processes, one that accumulates chloride and one that extrudes chloride.

Animals↗

Rat hippocampal neurons in culture: responses to electrical and chemical stimuli.

Intracellular activity was recorded from dissociated rat hippocampal neurons maintained in tissue culture conditions for 4-6 wk. The cells developed dense interconnections and had typical morphological characteristics similar to hippocampal neurons in situ. The recorded neurons possessed similar electrophysiological properties to those observed in situ or in a slice preparation. Their input resistance (42 M omega), resting membrane potential (-60 mV), membrane time constant (16.2 ms), total electrotonic length (0.92), and spike size (68.3 mV) were similar to values obtained in hippocampal cells in a slice. The connections among adjacent neurons were largely inhibitory. The inhibitory postsynaptic potentials (IPSPs) had longer durations than excitatory postsynaptic potentials (EPSPs) when these were detected. Synaptic delay varied between 0.3 and 3.0 ms. There were no electrotonic connections among neurons. Reciprocal connections were common. Most neurons reacted to acetylcholine (ACh) by an increase in frequency of spontaneous EPSPs, action-potential discharges, and IPSPs. Concurrently, there was a marked reduction in the magnitude of the evoked PSPs tested in pairs of cells. This effect is probably presynaptic to the recorded neurons. A statistical analysis of quantal properties of the synaptic interactions among neurons revealed that ACh causes a reduction of magnitude of PSPs by reducing the number of releasing elements (m). This effect is different from the reduction of evoked PSPs caused by postsynaptic depolarization.

Acetylcholine↗