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PubMed1991

Mechanisms underlying potentiation of synaptic transmission in rat anterior cingulate cortex in vitro.

1. The properties of the excitatory synapse made by callosal inputs onto layer V and layer VI cells in the anterior cingulate cortex were studied in an in vitro slice preparation with intracellular recording. 2. In the presence of picrotoxin, the excitatory postsynaptic potential (EPSP) had two components, a fast component blocked by the non-N-methyl-D-aspartate (NMDA) receptor antagonist 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX) and a slow component blocked by the NMDA receptor antagonist DL-2-amino-5-phosphonovalerate (APV). 3. Delivery of a brief tetanus to the afferent fibres led to a long-term potentiation (LTP) of the initial slope of the monosynaptic EPSP. The LTP displayed the property of co-operativity and could be blocked by APV or by buffering intracellular calcium. 4. Pairing of low frequency presynaptic activity or weak tetanic stimulation with postsynaptic depolarization failed to potentiate the EPSP. This suggests that postsynaptic depolarization alone is unable to explain the co-operativity. 5. It is concluded that the transmitter mediating the excitatory input between callosal afferents and layer V and layer VI pyramidal neurones is glutamate. Tetanic stimulation of these afferents leads to LTP which shares many but not all the properties of LTP seen in the CA1 region of the hippocampus.

2-Amino-5-phosphonovalerate↗
PubMed1992

Evidence that synaptic transmission between giant interneurons and identified thoracic interneurons in the cockroach is cholinergic.

In the cockroach, a population of thoracic interneurons (TIs) receives direct inputs from a population of ventral giant interneurons (vGIs). Synaptic potentials in type-A TIs (TIAs) follow vGI action potentials with constant, short latencies at frequencies up to 200 Hz. These connections are important in the integration of directional wind information involved in determining an oriented escape response. The physiological and biochemical properties of these connections that underlie this decision-making process were examined. Injection of hyperpolarizing or depolarizing current into the postsynaptic TIAs resulted in alterations in the amplitude of the post-synaptic potential (PSP) appropriate for a chemical connection. In addition, bathing cells in zero-calcium, high-magnesium saline resulted in a gradual decrement of the PSP, and ultimately blocked synaptic transmission, reversibly. Single-cell choline acetyltransferase (ChAT) assays of vGI somata were performed. These assays indicated that the vGIs can synthesize acetylcholine. Furthermore, the pharmacological specificity of transmission at the vGI to TIA connections was similar to that previously reported for nicotinic, cholinergic synapses in insects, suggesting that the transmitter released by vGIs at these synapses is acetylcholine.

Acetylcholine↗
PubMed2002

Synaptic pharmacology in the turtle accessory optic system.

The accessory optic system of the turtle (the basal optic nucleus, BON) receives both excitatory and inhibitory inputs that are direction-sensitive. When the dorsal midbrain is ablated, only the monosynaptic direction-sensitive input from the retina to the BON remains. To better understand the central visual processing performed by the accessory optic system, this study identifies the neurotransmitters and their receptors that mediate the synaptic excitation and inhibition of BON cells. We used a reduced in vitro turtle brainstem preparation in which the two eyes and brain were isolated pharmacologically. Patch recordings were made on BON neurons while drugs were applied to the brain, with the eyes bathed in control media and either exposed to visual pattern motion or subjected to electrical stimulation. An antagonist of the AMPA (alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid) subtype of glutamate receptor applied within the brain chamber blocked the visual responses. In response to electrical stimulation both excitatory and inhibitory synaptic events were blocked in BON cells, presumably by blocking direct excitation by retinal ganglion cell axons in the BON and indirect excitation of inhibitory interneurons elsewhere in the brainstem. An NMDA receptor antagonist was ineffective, even when the response was measured in a BON cell depolarized in Mg(2+)-free media. A GABA(A) receptor on the BON cell mediates the inhibitory responses to retinal stimulation. Injection of lidocaine into the contralateral eye caused an increase in spontaneous inhibitory post-synaptic potentials (IPSPs), suggesting that a tonic retinal output exists that reduces brainstem inhibition of BON cells. Also, there may be tonic inhibition of an excitatory path to BON neurons from within the brainstem, because bicuculline increased spontaneous excitatory post-synaptic potentials (EPSPs) observed in a BON cell without retinal input. These results indicate that the BON is a site of complex visual processing of competing visual signals and provide insight into how an interaction of excitation and inhibition creates a retinal slip signal in the accessory optic system.

2-Amino-5-phosphonovalerate↗
PubMed1996

Recombinant GABAA receptor desensitization: the role of the gamma 2 subunit and its physiological significance.

1. The purpose of these investigations was to examine the role that the gamma 2 subunit plays in human GABAA receptor desensitization. Two different recombinant GABAA receptors (alpha 1 beta 3 and alpha 1 beta 3 gamma 2) were compared by measuring the relaxation of whole-cell currents during the application of GABA, isoguvacine or taurine. 2. At concentrations which trigger a maximum response (100-500 microM GABA) the current relaxation usually fitted the sum of two exponentials. For alpha 1 beta 3 subunit receptors these values were tau 1 = 145 +/- 12 ms and tau 2 = 6.3 +/- 2.1 s (means +/- S.E.M.). Receptors consisting of alpha 1 beta 3 gamma 2 subunits desensitized faster: tau 1 = 41.6 +/- 8.3 ms and tau 2 = 2.4 +/- 0.6 s. 3. The Hill slope, determined for each receptor subunit combination, was the same and greater than 1.0, implying two binding steps in the activation of both receptor subunit combinations. 4. For alpha 1 beta 3 subunit receptors the fast desensitization rates were unaltered by reducing the GABA concentration from the EC100 (100 microM) to the approximate EC50 values (10-20 microM), whereas for alpha 1 beta 3 gamma 2 subunit receptors a significant slowing was observed. The fast desensitization disappeared at agonist concentrations below the EC50 for both subunit combinations. In contrast, the slow desensitization appeared at agonist concentrations near the EC20. This rate was dependent on agonist concentration reaching a maximum near the EC60 value of GABA. 5. The fast desensitization rates were unaltered by changing the holding potential of the cell during agonist application. However, for alpha 1 beta 3 gamma 2 subunit receptors the slow desensitization rate increased by approximately 15- to 20-fold over the range of voltages of -60 to +40 mV. This indicates that the gamma 2 subunit makes GABAA receptor desensitization voltage dependent. 6. Recovery from desensitization was also biphasic. The first recovery phase was faster for alpha 1 beta 3 gamma 2 than for alpha 1 beta 3 subunit receptors (0.13 vs. 0.03 s-1, respectively). The second phase of recovery for the two receptors were the same (approximately 0.003 s-1). 7. There was only a poor correlation between agonist potency and the degree or time course of desensitization. Isoguvacine (EC50 approximately to 10 microM) induced biphasic relaxation for both alpha 1 beta 3 and alpha 1 beta 3 gamma 2 subunit receptors (tau 1 = 288.6 +/- 43.3 and 167 +/- 15 ms, and tau 2 = 8.0 +/- 1.9 and 4.4 +/- 0.4 S, respectively, for each subunit combination). Taurine (EC50 approximately 7 mM) usually induced monophasic relaxation for both subunit combinations (tau 2 = 7.1 +/- 1.6 and 23.0 +/- 6.6 s, respectively). 8. A computer model was developed to examine the effect of the gamma 2 subunit on the time course of a synaptic potential. It was found that the gamma 2 subunit theoretically prolongs the time course of a synaptic potential by inducing desensitization more rapidly. The subsequent relaxation of the desensitized receptors through the open state increases Popen (the probability that the GABAA receptor is in an open conducting state) altering the time course of the modelled potential. alpha 1 beta 3 subunit receptors do not desensitize sufficiently rapidly to induce this desensitized state and, therefore, are shorter in time course. These data imply that the physiological role of the gamma 2 subunit is to increase synaptic efficacy by prolonging Popen.

Cells, Cultured↗
PubMed1984

Interneurones in the Xenopus embryo spinal cord: sensory excitation and activity during swimming.

The dorsolateral spinal cord of embryonic Xenopus laevis has previously been shown to contain two anatomical classes of interneurones with dendrites in the dorsal tract where they could be contacted by the central axons of Rohon-Beard cells (Roberts & Clarke, 1982). The activity of these neurones within the dorsolateral spinal cord has been examined using intracellular micro-electrodes. Following electrical stimulation of Rohon-Beard neurites within the ipsilateral skin, dorsolateral neurones receive a short-latency, compound, excitatory post-synaptic potential (e.p.s.p.). The amplitude of the e.p.s.p. depends upon the number of Rohon-Beard cells stimulated. The e.p.s.p. consists of early and later components. The early components may result from monosynaptic connexions from Rohon-Beard cells, the later components from some unidentified interposed neurones. During episodes of fictive swimming the dorsolateral neurones are inhibited by rhythmic inhibitory post-synaptic potentials. Following Rohon-Beard neurite stimulation, neurones in the contralateral spinal cord receive e.p.s.p.s. These contralateral e.p.s.p.s are probably one of the post-synaptic effects of one of the dorsolateral neurone classes. The results suggest that the dorsolateral neurones are responsible for amplifying and distributing the primary afferent signals of Rohon-Beard cells, and may be involved in the initiation of swimming and reflex movements.

Animals↗
PubMed1993

Dopamine D1 receptors facilitate transmitter release.

A physiological role for the dopamine D1 receptor has been difficult to define, particularly because of its complex pre- and postsynaptic localization in brain areas such as the striatum. In the midbrain, however, D1 receptors are selectively localized to the terminals of GABA (gamma-aminobutyric acid)-containing afferents. We have studied the actions of these D1 receptors on evoked GABA synaptic potentials recorded intracellularly from dopamine neurons in the ventral tegmental area (VTA). We report here that dopamine augmented GABAB inhibitory postsynaptic potentials (i.p.s.ps) in the presence of D2 receptor antagonists. This effect was mimicked by the D1 agonists SKF38393 and SKF82958 and blocked by the D1 antagonists SCH23390 and cis-flupenthixol. No modulation of the GABAA synaptic potential was observed. The postsynaptic actions of the GABAB agonist, baclofen, were unaffected by SKF38393, SCH23390 or cis-flupenthixol, confirming a presynaptic locus of D1 action. Additionally, D1 antagonists reduced the amplitude of the GABAB i.p.s.p. in the absence of D1 agonists. We conclude that dopamine acts tonically at presynaptic D1 receptors on the terminals of afferent GABA neurons to facilitate selectively GABAB-mediated neurotransmission in the midbrain.

Animals↗
PubMed1996

Electrophysiological mapping of fast excitatory synaptic inputs to morphologically and chemically characterized myenteric neurons of guinea-pig small intestine.

Neurons within the myenteric plexus of the guinea-pig ileum were impaled using conventional intracellular electrodes. Points of stimulation within the surrounding ganglia and connectives which gave rise to fast excitatory synaptic potentials were mapped using a movable monopolar stimulating electrode. Cells were then injected with the intracellular marker, biocytin, and processed for multiple label immunohistochemistry to reveal their morphologies, chemical contents and, hence, their functional classes. Of 65 neurons belonging to the S electrophysiological class, 53 received fast excitatory synaptic inputs from stimulation at sites at least 2 mm away in a directly circumferential direction. These inputs almost certainly arise from stimulation of the circumferentially-directed axons of the Dogiel type II/AH-neurons, which are thought to be intrinsic sensory neurons. The majority of cells which projected anally and were immunoreactive for nitric oxide synthase (19/25), all neurons which ramified in the tertiary plexus and were identified as longitudinal muscle motor neurons (6/6) and all neurons identified as excitatory motor neurons innervating the circular muscle (12/12) received inputs from these circumferentially-directed pathways. However only one of six descending filamentous interneurons impaled received such inputs, suggesting they may be differentially innervated. The conduction velocities of circumferentially-directed axons giving rise to fast excitatory post synaptic potentials were estimated to be 0.41 +/- 0.10 m/s (mean +/- standard deviation, n = 21). The conduction velocities estimated for longitudinally-directed pathways were 0.55 +/- 0.25 m/s (n = 29). Thus, the majority of myenteric neurons receive fast excitatory synaptic input from putative intrinsic sensory neurons which project circumferentially around the intestine.

Animals↗
PubMed1990

Developmental changes in serotonin actions in rat hippocampus.

Intracellular activity was recorded from neurons in immature rat hippocampal slices. The presence of intrinsic inhibitory synaptic potentials as well as responses to serotonin were assessed in slices of 1, 2 or 3 postnatal weeks of age. Young (1 week) cells had only a marginal hyperpolarizing response to serotonin and no detectable intrinsic inhibitory synaptic potentials. At 2 weeks of age neurons already expressed a fast IPSP (inhibitory postsynaptic potential). The responses to serotonin were different from those of adult cells in that they involved primarily a large decrease in input resistance with only small potential changes. In cells of this age serotonin caused a marked increase in spontaneous IPSP discharges and a blockade of a slow afterhyperpolarization. In 3-week-old rats the fast and slow components of the IPSP were present as in adult and the responses to serotonin included a large hyperpolarization associated with an increase in K conductance, a blockade of slow afterhyperpolarization and a blockade of a slow IPSP, as seen in adult cells. These results indicate that the complex pattern of reactivity to serotonin is differentially regulated in the developing brain.

Action Potentials↗
PubMed1994

Synaptic activation of metabotropic glutamate receptors in the parallel fibre-Purkinje cell pathway in rat cerebellar slices.

Glutamate, the major excitatory neurotransmitter in the central nervous system, acts through two broad classes of receptors: ion channel-linked (ionotropic) receptors, which include N-methyl-D-aspartate and alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors, and metabotropic receptors which couple via G-proteins to intracellular messenger cascades. Seven subtypes of mGluR are known to exist but their roles in synaptic physiology are poorly understood. In cerebellar Purkinje cells, application of the mGluR agonist, trans-1-aminocyclopentane-1,3-dicarboxylic acid, or the active enantiomer, 1S,3R-ACPD, results in a depolarization associated with an inward current and an elevation of intracellular Ca2+ (for review see Ref. 29). Moreover, using an extracellular (grease-gap) technique that monitors population responses, we have previously discovered that, in Purkinje cells of adult rat cerebellum, brief tetanic stimulation of the glutamatergic parallel fibre input gives rise to a slow depolarising synaptic potential that is resistant to ionotropic glutamate receptor blockers and to antagonists acting at GABA receptors. It was suggested that this novel potential is mediated by metabotropic receptors. The advent of antagonists for metabotropic receptors has allowed us to test this hypothesis. We find that the S-enantiomer of alpha-methyl-4-carboxyphenylglycine stereoselectively antagonizes the slow synaptic potential recorded using the grease-gap method. The results were confirmed by intracellular recording from Purkinje cells. To our knowledge this is the first direct evidence of an mGluR-mediated EPSP in intact brain tissue.

Animals↗
PubMed1983

Capsaicin causes release of a substance P-like peptide in guinea-pig inferior mesenteric ganglia.

The effects of capsaicin (0.5-100 microM) on neurones of the isolated inferior mesenteric ganglia (i.m.g.) of the guinea-pig were investigated by means of intracellular recording techniques. When applied to neurones of the i.m.g. that exhibited a slow non-cholinergic excitatory potential (Dun & Jiang, 1982), capsaicin caused in the large majority of these cells a long lasting depolarization accompanied by intense neuronal discharges. During and immediately following the depolarization, repetitive presynaptic stimulation consistently failed to elicit the non-cholinergic depolarization; a partial recovery was observed in relatively few neurones. The fast (nicotinic) excitatory post-synaptic potentials (e.p.s.p.s) were not suppressed by capsaicin in any of these cells. The membrane potential, input resistance and the amplitude of fast e.p.s.p.s in neurones of the i.m.g. that generated no detectable non-cholinergic depolarizations were not affected by capsaicin. Post-synaptic membrane sensitivity to exogenous application of substance P was not altered following capsaicin superfusion even though the latter effectively abolished the non-cholinergic depolarization in the same neurones. Superfusing the i.m.g. with a Ca-free Krebs solution markedly attenuated or abolished the depolarizing effect of capsaicin whereas tetrodotoxin (1 microM) was without effect. Capsaicin was without effect in a few neurones that generated a non-cholinergic depolarization; the latter was not desensitized by bath application of substance P. Capsaicin caused no appreciable effects in neurones of the bullfrog sympathetic ganglia; thus, the fast and slow post-synaptic potentials including the late slow e.p.s.p. the transmitter of which is the peptide luteinizing hormone-releasing hormone (Jan & Jan, 1982) were not affected. The results suggest that the depolarizing effect of capsaicin in neurones of the guinea-pig i.m.g. is due to a selective release of ganglionic substance P or a substance P-like peptide in a Ca-dependent manner, and that the non-cholinergic potentials elicited in capsaicin-insensitive neurones may be generated by a transmitter(s) other than substance P.

Action Potentials↗
PubMedDate not supplied

Model of global spontaneous activity and local structured activity during delay periods in the cerebral cortex.

We investigate self-sustaining stable states (attractors) in networks of integrate-and-fire neurons. First, we study the stability of spontaneous activity in an unstructured network. It is shown that the stochastic background activity, of 1-5 spikes/s, is unstable if all neurons are excitatory. On the other hand, spontaneous activity becomes self-stabilizing in presence of local inhibition, given reasonable values of the parameters of the network. Second, in a network sustaining physiological spontaneous rates, we study the effect of learning in a local module, expressed in synaptic modifications in specific populations of synapses. We find that if the average synaptic potentiation (LTP) is too low, no stimulus specific activity manifests itself in the delay period. Instead, following the presentation and removal of any stimulus there is, in the local module, a delay activity in which all neurons selective (responding visually) to any of the stimuli presented for learning have rates which gradually increase with the amplitude of synaptic potentiation. When the average LTP increases beyond a critical value, specific local attractors (stable states) appear abruptly against the background of the global uniform spontaneous attractor. In this case the local module has two available types of collective delay activity: if the stimulus is unfamiliar, the activity is spontaneous; if it is similar to a learned stimulus, delay activity is selective. These new attractors reflect the synaptic structure developed during learning. In each of them a small population of neurons have elevated rates, which depend on the strength of LTP. The remaining neurons of the module have their activity at spontaneous rates. The predictions made in this paper could be checked by single unit recordings in delayed response experiments.

Cerebral Cortex↗
PubMed1986

Amino acid receptor-mediated transmission at primary afferent synapses in rat spinal cord.

Intracellular recording techniques have been used to provide information on the identity of excitatory transmitters released at synapses formed between dorsal root ganglion (DRG) and spinal cord neurones in two in vitro preparations. Explants of embryonic rat DRG were added to dissociated cultures of embryonic dorsal horn neurones and synaptic potentials recorded intracellularly from dorsal horn neurones after DRG explant stimulation. More than 80% of dorsal horn neurones received at least one fast, DRG-evoked, monosynaptic input. In the presence of high divalent cation concentrations (5 mmol l-1 Ca2+, 3 mmol l-1 Mg2+) the acidic amino acid receptor agonists, L-glutamate, kainate (KA) and quisqualate (QUIS) excited all dorsal horn neurones which received a monosynaptic DRG neurone input, whereas L-aspartate and N-methyl-D-aspartate (NMDA) had little or no action. 2-Amino-5-phosphonovalerate (APV), a selective NMDA receptor antagonist, was relatively ineffective at antagonizing DRG-evoked synaptic potentials and L-glutamate-evoked responses. In contrast, kynurenate was found to be a potent antagonist of amino acid-evoked responses and of synaptic transmission at all DRG-dorsal horn synapses examined. The blockade of synaptic transmission by kynurenate appeared to result from a postsynaptic action on dorsal horn neurones. Intracellular recordings from motoneurones in new-born rat spinal cord were used to study the sensitivity of the Ia excitatory postsynaptic potential (EPSP) to antagonists of excitatory amino acids. Superfusion of the spinal cord with APV did not inhibit the Ia EPSP but did suppress later, polysynaptic components of the afferent-evoked response. Kynurenate was a potent and selective inhibitor of the Ia EPSP, acting via a postsynaptic mechanism. These findings indicate that L-glutamate, or a glutamate-like compound, but not L-aspartate, is likely to be the predominant excitatory transmitter that mediates fast excitatory postsynaptic potentials at primary afferent synapses with both dorsal horn neurones and motoneurones.

Afferent Pathways↗
PubMed2005

Homosynaptic and heterosynaptic inhibition of synaptic tagging and capture of long-term potentiation by previous synaptic activity.

Long-term potentiation (LTP) is an enhancement of synaptic strength that may contribute to information storage in the mammalian brain. LTP expression can be regulated by previous synaptic activity, a process known as "metaplasticity." Cell-wide occurrence of metaplasticity may regulate synaptic strength. However, few reports have demonstrated metaplasticity at synapses that are silent during activity at converging synaptic inputs. We describe a novel form of cell-wide metaplasticity in hippocampal area CA1. Low-frequency stimulation (LFS) decreased the stability of long-lasting LTP ["late" LTP (L-LTP)] induced later at the same inputs (homosynaptic inhibition) and at other inputs converging on the same postsynaptic cells (heterosynaptic inhibition). Significantly, heterosynaptic inhibition of L-LTP also occurred across basal and apical dendrites ("heterodendritic" inhibition). Because transient early LTP (E-LTP) was not affected by previous LFS, we examined the effects of LFS on the consolidation of E-LTP to L-LTP. The duration of E-LTP induced at one set of inputs can be extended by capturing L-LTP-associated gene products generated by previous activity at other inputs to the same postsynaptic neurons. LFS applied homosynaptically or heterosynaptically before L-LTP induction did not impair synaptic capture by subsequent E-LTP stimulation, suggesting that LFS does not impair L-LTP-associated transcription. In contrast, LFS applied just before E-LTP (homosynaptically or heterosynaptically) prevented synaptic tagging, and capture of L-LTP expression. Thus, LFS inhibits synaptic tagging to impair expression of subsequent L-LTP. Such anterograde inhibition represents a novel way in which synaptic activity can regulate the expression of future long-lasting synaptic plasticity in a cell-wide manner.

Animals↗
PubMed1998

NIK-247 induces long-term potentiation of synaptic transmission in the CA1 region of rat hippocampal slices through M2 muscarinic receptors.

1. The purpose of this study was to examine whether NIK-247 can, by itself, induce long-lasting changes in synaptic efficacy in the hippocampus. Population spikes evoked by electrical stimulation of the stratum radiatum were recorded in the pyramidal cell layer of the CA1 region of the isolated hippocampus. 2. NIK-247 at 1 x 10(-7) - 1 x 10(-5) M dose dependently increased the amplitude of these spikes. The increase in population spikes by NIK-247 outlasted, for 2 hr, its presence. In addition, the increase in population spikes recovered to 2 hr after washout of NIK-247. Therefore, it was concluded that NIK-247 induced long-term potentiation (LTP) by itself. However, tacrine and physostigmine at 1 x 10(-7) - 1 x 10(-5) M did not increase the amplitude of population spikes and did not induce LTP by themselves. 3. The increase in amplitude of population spikes induced by NIK-247 was completely blocked sensitively by atropine (IC50 = 4.3 x 10(-8)M) but insensitively by pirenzepine (IC50 = 9.1 x 10(-7) M). Carbachol also increased the amplitude of population spikes in the presence of pirenzepine. 4. These findings indicate that the LTP induced by NIK-247 is due to its M2 muscarinic agonistic effect in the CA1 region of the rat hippocampus. It is expected that NIK-247 may be useful for the treatment of Alzheimer disease.

(4-(m-Chlorophenylcarbamoyloxy)-2-butynyl)trimethy↗
PubMed1997

Computer simulation of the enteric neural circuits mediating an ascending reflex: roles of fast and slow excitatory outputs of sensory neurons.

Recent electrophysiological studies of the properties of intestinal reflexes and the neurons that mediate them indicate that the intrinsic sensory neurons may transmit to second order neurons via either fast (30-50 ms duration) or slow (10-60 s duration) excitatory synaptic potentials or both. Which of these possible modes of transmission is involved in the initiation of motility reflexes has not been determined and it is not clear and what the consequences of the different forms of synaptic transmission would be for the properties of the reflex pathways. In the present study, this question has been addressed by the use off a suite of computer programs, Plexus, which was written to simulate the activity of the neurons of the enteric nervous system during intestinal reflexes. The programs construct a simulated enteric nerve circuit based on anatomical and physiological data about the number, functions and interconnections of neurons involved in the control of motility. The membrane potentials of neurons are calculated individually from physiological data about the reversal potentials and membrane conductances for Na+, K+ and Cl-. Synaptic potentials are simulated by changes in specific conductances based on physiological data. The results of each simulation are monitored by recording the membrane potentials of up to 16 separate defined neurons and by recording the summed activity of whole classes of neurons as a function of time and location in the stimulated network. The present series of experiments simulated the behaviour of a network consisting of 18,898 sensory neurons and 3708 ascending interneurons after 75% of the sensory neurons lying in the anal 10 mm of a 30 mm long segment of small intestine were stimulated once. The results were compared with electrophysiological data recorded from myenteric neurons during ascending reflexes evoked either by distension or mechanical stimulation of the mucosa. When transmission from sensory neurons to ascending interneurons was via fast excitatory synaptic potentials, the latencies and durations of the simulated responses were too brief to match the electrophysiologically recorded responses. When transmission from sensory neurons was via slow excitatory synaptic potentials, the latencies were very similar to those recorded physiologically, but the durations of the stimulated responses were much longer than seen in physiological experiments. The latencies and durations of simulated and physiologically recorded responses matched only when the firing of ascending interneurons was limited to the beginning of a slow excitatory synaptic (in this study by limiting the duration of the decrease in K+ conductance). The simulation provided several physiologically testable predictions, indicating that Plexus is an important tool for the investigation of the properties and behaviour of the enteric nervous system.

Computer Simulation↗
PubMed2002

Moderate hypoglycemia aggravates effects of hypoxia in hippocampal slices from diabetic rats.

We recorded the effects of hypoxia combined with relative hypoglycemia on pre- and post-synaptic potentials in the CA1 area of slices from 4-month-old control and diabetic (streptozotocin-treated) Wistar rats. In experiments on slices kept in 10 or 4 mM glucose (at 33 degrees C), hypoxia was applied until the pre-synaptic afferent volley disappeared--after 12-13 min in most slices, but much earlier (5+/-0.8 min) in diabetic slices kept in 4 mM glucose. When oxygenation was resumed, the afferent volley returned in all slices, for an overall mean recovery of 86.5% (+/-8.8%). Field post-synaptic potentials were fully blocked within 2-3 min of the onset of hypoxia. After the end of hypoxia, they failed to reappear in some slices: overall, their recovery varied between 62 and 68% in control slices, as well as in diabetic slices kept in 10 mM glucose; but recovery was very poor in diabetic slices kept in 4 mM glucose (only 15+/-0.94%). In the latter, hypoxic injury discharges occurred earlier (4.2+/-0.68 min vs. 6.5-8 min for other groups). We conclude that diabetes appears to make hippocampal slices more prone to irreversible loss of synaptic function and early block of axonal conduction when temporary hypoxia is combined with moderate hypoglycemia.

Animals↗
PubMedDate not supplied

Recurrent neural networks of integrate-and-fire cells simulating short-term memory and wrist movement tasks derived from continuous dynamic networks.

Dynamic recurrent neural networks composed of units with continuous activation functions provide a powerful tool for simulating a wide range of behaviors, since the requisite interconnections can be readily derived by gradient descent methods. However, it is not clear whether more realistic integrate-and-fire cells with comparable connection weights would perform the same functions. We therefore investigated methods to convert dynamic recurrent neural networks of continuous units into networks with integrate-and-fire cells. The transforms were tested on two recurrent networks derived by backpropagation. The first simulates a short-term memory task with units that mimic neural activity observed in cortex of monkeys performing instructed delay tasks. The network utilizes recurrent connections to generate sustained activity that codes the remembered value of a transient cue. The second network simulates patterns of neural activity observed in monkeys performing a step-tracking task with flexion/extension wrist movements. This more complicated network provides a working model of the interactions between multiple spinal and supraspinal centers controlling motoneurons. Our conversion algorithm replaced each continuous unit with multiple integrate-and-fire cells that interact through delayed "synaptic potentials". Successful transformation depends on obtaining an appropriate fit between the activation function of the continuous units and the input-output relation of the spiking cells. This fit can be achieved by adapting the parameters of the synaptic potentials to replicate the input-output behavior of a standard sigmoidal activation function (shown for the short-term memory network). Alternatively, a customized activation function can be derived from the input-output relation of the spiking cells for a chosen set of parameters (demonstrated for the wrist flexion/extension network). In both cases the resulting networks of spiking cells exhibited activity that replicated the activity of corresponding continuous units. This confirms that the network solutions obtained through backpropagation apply to spiking networks and provides a useful method for deriving recurrent spiking networks performing a wide range of functions.

Animals↗
PubMed1993

Purine release and inhibition of synaptic transmission during hypoxia and hypoglycemia in rat hippocampal slices.

Evoked synaptic potentials and purine efflux were measured simultaneously from rat hippocampal slices. Slices were exposed to hypoxia, to glucose-free medium, and to in vitro ischemia consisting of glucose-free, hypoxic medium. During exposure to hypoxia or the glucose-free condition, radiolabelled purine efflux increased and the evoked population spike declined. Synaptic potentials and purine efflux returned to baseline values after reintroduction of normoxic and normoglycemic medium. During exposure to in vitro ischemia, purine and adenosine efflux were greatly increased with the appearance of the anoxic depolarization.

Adenine↗