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PubMedDate not supplied

Hyperpolarization following activation of K+ channels by excitatory postsynaptic potentials.

We have postulated that an excitatory postsynaptic potential (e.p.s.p.) may open voltage-sensitive K+ ('M') channels, in an appropriate depolarizing range, and that this could alter the e.p.s.p. waveform. Consequently, the fast e.p.s.p. in neurones of sympathetic ganglia, elicited by a nicotinic action of acetylcholine (ACh), could be followed by a hyperpolarization, produced by the opening of M channels during the depolarizing e.p.s.p. and their subsequent slow closure (time constant-150 mg). This introduces the concept that transmitter-induced p.s.ps may trigger voltage-sensitive conductances other than those initiating action potentials, and that in the present case this could produce a true post-e.p.s.p. hyperpolarization. (Some hyperpolarizations other than inhibitory postsynaptic potentials (i.p.s.ps) have been reported to follow e.p.s.ps.) We show here that this is so.

Animals↗

PubMed1996

Block of glutamate decarboxylase decreases GABAergic inhibition at the crayfish synapses: possible role of presynaptic metabotropic mechanisms.

1. The cytosolic concentration of a neurotransmitter is believed to be an important factor determining its release. The effects of 3-mercaptopropionic acid (MP) and aminooxyacetic acid (AOAA), glutamate decarboxylase (GAD) blockers, on GABAergic postsynaptic and presynaptic inhibitory neurotransmission were examined in the crayfish (Procambarus clarkii) opener neuromuscular synapses. 2. Intracellular recordings of evoked excitatory postsynaptic potentials (EPSPs) and inhibitory postsynaptic potentials (IPSPs) as well as loose macropatch clamp measurements of excitatory postsynaptic currents (EPSCs) and inhibitory postsynaptic currents (IPSCs) were used to evaluate the effects of the drugs, which were applied exclusively to the nerve bundle. 3. Under normal conditions, a stimulus train to the inhibitor preceding the excitor stimulation elicited a large reduction in EPSP amplitude in a time interval-dependent manner. This inhibition is effected by postsynaptic as well as presynaptic processes. 4. Treatment with MP or AOAA decreased the IPSP amplitude and its altered conductance but had no effect on the IPSP reversal potential or the resting potential of the cell. They did, however, slightly increase the Rin of the fiber. 5. Quantal analysis of single IPSCs revealed that GAD blockers increased the number of failures and thus reduced quantal content (m), diminished the probability of release (p), but did not affect the quantum current (q) or the statistical parameter (n), believed to be the number of available active zones. 6. Quantal analysis of EPSCs, released after interaction with the inhibitor, revealed a reduction in m without any effect on q. GAD blockers greatly reduced the efficacy of this inhibition without affecting the EPSC q. 7. GAD blockers increased the output of the excitor release sites by the following mechanisms: 1) increased EPSC, 2) increased EPSC facilitation, or 3) enhancement of spontaneous activity (miniature EPSCs). 8. Short time incubation with picrotoxin and CGP-35348 eliminated IPSCs and evoked inhibition. However, longer exposure (90 min) increased the excitor responses, similarly to the effects of GAD blockers. 9. Baclofen, a gamma-aminobutyric acid-B (GABAB) agonist, antagonized AOAA effects on evoked inhibition. 10. These results demonstrate that GAD blockers decrease postsynaptic and presynaptic inhibition by reducing both tonic and evoked release, most likely by diminishing p. 11. The reduction in GABA synthesis and release revealed a complex mechanism for GABAergic metabotropic regulation of inhibition efficacy and the release from the excitor glutamatergic terminals.

3-Mercaptopropionic Acid↗

PubMed1999

IL-1beta and IL-6 excite neurons and suppress nicotinic and noradrenergic neurotransmission in guinea pig enteric nervous system.

Conventional intracellular microelectrodes and injection of biocytin were used to study the actions of IL-1beta and IL-6 on electrical and synaptic behavior in morphologically identified guinea pig small intestinal submucous neurons. Exposure to nanomolar concentrations of either IL-1beta or IL-6 stimulated neuronal excitability. The excitatory action consisted of depolarization of the membrane potential, decreased membrane conductance, and increased discharge of action potentials. Excitatory action of IL-1beta was suppressed by the natural IL-1beta human receptor antagonist. Electrical stimulation of sympathetic postganglionic axons evoked inhibitory postsynaptic potentials (IPSPs), and stimulation of cholinergic axons evoked nicotinic fast excitatory postsynaptic potentials (EPSPs). Both kinds of synaptic potentials occurred in neurons with uniaxonal morphology believed to be secretomotor neurons. Either IL-1beta or IL-6 suppressed the noradrenergic IPSPs and the fast EPSPs, and the two acted synergistically when applied in combination. Suppression of the IPSP resulted from presynaptic inhibition of the release of norepinephrine from sympathetic nerves. The results suggest that the presence of either or both inflammatory cytokines will release the sympathetic brake from secretomotor neurons to the intestinal crypts and from nicotinic synapses in the integrative microcircuits, where norepinephrine is known to have a presynaptic inhibitory action. This, in concert with excitation of secretomotor neurons, may lead to neurogenic secretory diarrhea.

Animals↗

PubMed1983

The mode of nigro-thalamic transmission investigated with intracellular recording in the cat.

Postsynaptic potentials evoked by stimulating the substantia nigra (SN) were recorded intracellularly from ipsilateral ventral medial (VM), ventral lateral (VL), and ventral anterior (VA) nuclei of the thalamus in cats anesthetized with sodium pentobarbital. SN stimulation evoked inhibitory postsynaptic potentials (IPSP) at a short latency in VM neurons (mean 1.68 ms, SD 0.23, n = 59). The IPSP were produced monosynaptically because linear regression analysis of latency vs. conduction distance between stimulating and recording sites indicated a synaptic delay of less than 0.6 ms. Conduction velocity for these fibers was calculated to be 4.48 m/s. The spots from which IPSP were produced with the lowest threshold were determined for each of 38 VM neurons. IPSP origins thus determined were distributed in the pars reticulata of the SN (SNr) and in the area where nigro-thalamic fibers run. Neurons which received IPSP from the SNr were distributed in the VM nucleus, ventromedial to the VL nucleus, where fibers from the contralateral brachium conjunctivum terminate. Convergence of nigral and cerebellar impulses was not observed in thalamic neurons sampled in this study. Stimulation of the entopeduncular nucleus (ENT) also produced monosynaptic IPSP in VL-VA neurons. The SNr-related cell group was located ventromedially and caudally to the ENT-related cell group. No convergence of nigral and pallidal influences was observed within thalamic neurons.

Animals↗

PubMed1994

A biologically motivated and analytically soluble model of collective oscillations in the cortex. II. Application to binding and pattern segmentation.

Feature linking and pattern separation are shown to be performed as simultaneous processes by a highly connected auto-associative network of spiking neurons (spike response model). In principle, many (e.g., with nine) patterns can be separated, but with a biological set of parameters the number is limited to four. The patterns have been learned by an asymmetric hebbian rule that can handle a low activity which may vary from pattern to pattern (in a range between 4% and 7%). Spikes are generated by a threshold process and--with some delay--transmitted to postsynaptic neurons. There they evoke an excitatory or inhibitory postsynaptic potential (EPSP or IPSP). Spike emission is followed by an absolute refractory period (1 ms) and activates an inhibitory delay loop that prevents continuous firing. Three different network topologies are discussed, i.e., a structureless fully connected system, a network composed of two 'hemispheres', and finally a hierarchical network with four subsystems that represent different 'functions' and interact via feedforward and feedback connections. Functional feedback turns out to be essential for context-sensitive binding. The coherence between the two hemispheres is dependent on the interhemispheric delays. If these are on average too large, the two hemispheres oscillate coherently by themselves but phase-shifted by half a period with respect to each other.

Animals↗

PubMed1990

Activity-dependent ionic changes and neuronal plasticity in rat hippocampus.

We describe here the ionic changes which occur during repetitive stimulation of a type which will induce long-term potentiation and kindling plasticity. The causes of these ionic changes, particularly of changes in [Ca2+]o, are discussed. Evidence will be presented which shows that only a fraction of the decreases in [Ca2+]o is due to movement through N-methyl-D-aspartate (NMDA)-operated channels. Since NMDA-receptor activation is critical in many synapses for induction of long-term potentiation (LTP) and since the initial response to a stimulus in hippocampus is a long-lasting slow inhibitory postsynaptic potential (IPSP), mechanisms must be defined which ultimately permit activation of NMDA receptors. We conclude that increases in [K+]o and reductions in [Ca2+]o and [Mg2+]o, together with a K(+)-dependent reduction of slow IPSP promote the activation of NMDA receptors during a stimulus train and help to overcome the blocking effect which the long-lasting hyperpolarizations exert on NMDA receptors. Preliminary evidence derived from analysis of quisqualate and NMDA-induced changes in [Ca2+]o suggests that NMDA-receptor activation slows the extrusion of Ca2+ from cells. This mechanism may be important for induction of long-term changes. Finally, we document that a number of long-term changes in neuronal excitability are associated with alterations of stimulus and excitatory amino acid (EAA)-induced changes in the ionic microenvironment, which give some insight into the mechanisms underlying stimulus-induced plasticity and, perhaps, progression of temporal lobe epilepsy.

Animals↗

PubMed1985

Synaptic potentials in motoneurons during fictive swimming in spinal Xenopus embryos.

Embryos spinalized at the 3rd to 6th postotic myotome and immobilized in 10(-4) M tubocurarine can respond to a brief skin stimulus with motor root activity suitable for swimming. Embryos spinalized at the more caudal levels give shorter episodes of fictive swimming. We have previously described the synaptic inputs to motoneurons during fictive swimming in intact embryos (23). In the present paper we look to see if similar synaptic inputs are present in spinal embryos and are therefore spinal in origin. All motoneuron firing during fictive swimming is associated with a tonic depolarization that falls away slowly once firing stops, is increased by hyperpolarizing current, and is reduced by depolarizing current. A slow depolarizing potential evoked by lower levels of skin stimulation has similar properties and rate of fall. In 1-2 mM PDA, an excitatory amino acid antagonist, only a small remnant of the depolarization remains, and motoneuron firing stops. The NMDA antagonist 50 microM APV reduces the depolarization less but also blocks firing. Motoneurons fire one spike per swimming cycle, in phase with nearby motor root discharge. Spikes are preceded by a depolarizing prepotential. This increases with hyperpolarizing current, which can block the spike to reveal an underlying depolarizing potential. In phase with motor root discharge on the opposite side of the body, motoneurons receive a midcycle inhibitory postsynaptic potential, which increases with depolarizing current, decreases with hyperpolarizing current, and is blocked by 10(-6) M strychnine. Strychnine, 5 X 10(-7) M, leads first to broadening of motor root bursts then to loss of the alternating swimming pattern of activity, which is replaced by synchronous bursts on both sides of the body. We conclude that the synaptic inputs to motoneurons during fictive swimming in spinal embryos are very similar in properties and pharmacology to those in intact embryos. These inputs, including the tonic depolarization always associated with motoneuron firing during swimming, must be at least partly spinal in origin.

Amino Acids↗

PubMed1992

Excitatory postsynaptic potentials recorded from regular-spiking cells in layers II/III of rat sensorimotor cortex.

1. Intracellular recording techniques were used to investigate the physiological and pharmacological properties of stimulus-induced excitatory postsynaptic potentials (EPSPs) recorded in regular-spiking cells located in layers II/III of rat sensorimotor cortical slices maintained in vitro. 2. Depending on the strength of the extracellular stimuli, a pure EPSP or an EPSP-inhibitory postsynaptic potential sequence was observed under perfusion with normal medium. The EPSPs displayed short latency of onset [2.4 +/- 0.7 (SD) ms] and were able to follow repetitive stimulation (tested less than or equal to 5 Hz). Variation of the membrane potential (Vm) revealed two types of voltage behavior for the short-latency EPSP. The first type decreased in amplitude with depolarization and increased in amplitude with hyperpolarization. In contrast, the second type behaved anomalously by increasing and decreasing in size after depolarization and hyperpolarization, respectively. 3. Several experimental procedures were carried out to investigate the mechanism underlying the anomalous voltage behavior of the EPSP. Results indicated that this type of Vm dependency could be mimicked by an intrinsic response evoked by a brief pulse of depolarizing current and could be abolished by N-(2,6-dimethylphenylcarbamoylmethyl)triethylammonium bromide (50 mM). Furthermore, the EPSP was not sensitive to the N-methyl-D-aspartate (NMDA) receptor antagonist 3-((+-)-2-carboxypiperazin-4-yl)-propyl-1-phosphonate (CPP, 10 microM). Thus the anomalous voltage relationship of the neuronal membrane. 4. The involvement of non-NMDA receptors in excitatory synaptic transmission was investigated with their selective antagonist 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX, 1-10 microM). This drug greatly reduced or completely blocked the EPSP in a dose-dependent manner (1-10 microM). The IC50 for the CNQX effect was approximately 2 microM. In the presence of CNQX (10 microM) and glycine (10 microM), synaptic stimulation failed to elicit firing of action potential. However, a CPP-sensitive EPSP was observed. 5. When synaptic inhibition was reduced by low concentration of bicuculline methiodide (BMI, 1-2 microM), extracellular stimulation revealed late EPSPs (latency to onset: 10-30 ms) that were not discernible in normal medium. Similar to the short-latency EPSP, the Vm dependency displayed by this late EPSP could be modified by inward membrane rectifications. The late EPSP appeared to be polysynaptic in origin because 1) its latency of onset was long and variable and 2) it failed to follow repetitive stimuli delivered at a frequency that did not depress the short-latency EPSP.(ABSTRACT TRUNCATED AT 400 WORDS)

6-Cyano-7-nitroquinoxaline-2,3-dione↗

PubMed1995

Properties of networks controlling locomotion and significance of voltage dependency of NMDA channels: stimulation study of rhythm generation sustained by positive feedback.

1. We have built a realistic 24-neuron model based on data from the spinal pattern generator for swimming in Xenopus embryos with the use of the SWIM programs. The neurons have dendrite, soma, and axon compartments with voltage-gated Na+ and K+ channels. Dendritic synapses were modeled as modulated ionic conductances with currents that have different reversal levels. One of these conductances was voltage dependent to model N-methyl-D-aspartate ("NMDA") synapses in the presence of Mg2+. 2. In this model, rhythm generation is initiated by a brief excitation, depends on rebound from reciprocal inhibition, and is sustained by long-duration "NMDA-dependent" feedback excitation. 3. Without NMDA voltage dependency, rhythmic activity is stable over a wide range of synaptic conductances. Its frequency decreases with more inhibition and increases with more excitation. The introduction of normally distributed variation in soma size or excitatory synaptic conductance extends the lower stable frequency range. Without such variation the frequency of the 24-neuron model is the same as a 4-neuron model provided that the synaptic conductances for each neuron are the same. 4. The effect of introducing NMDA voltage dependency on rebound after negative current injections or synaptic inhibition was investigated in single depolarized model neurons. With NMDA voltage dependency, hyperpolarizations and rebound spike responses were increased. 5. Network activity with NMDA voltage dependency was similar to that without it, but inhibitory postsynaptic potentials (IPSPs) and spikes were larger, and frequencies were lower and more sensitive to changes in excitatory and inhibitory conductance. 6. We conclude that in the model, mutual reexcitation among excitatory spinal interneurons can sustain rhythm generation by positive feedback and that NMDA voltage dependency can enhance postinhibitory rebound, stabilize swimming activity and extend its lower frequency range, and steepen the dependency of frequency on synaptic drive.

Animals↗

PubMed1996

IPSPs modulate spike backpropagation and associated [Ca2+]i changes in the dendrites of hippocampal CA1 pyramidal neurons.

1. We studied the effects of synaptic inhibition on backpropagating Na+ spikes in the apical dendrites of CA1 pyramidal neurons in transverse slices from the rat hippocampus. Action potentials were evoked synaptically by stimulation in the stratum radiatum or antidromically by stimulation in the alveus. 2. Inhibitory postsynaptic potentials, evoked by stimulation in the stratum lacunosum moleculare, reduced the amplitude of single spikes in the distal dendrites but did not change the amplitudes in the somatic or proximal regions. Inhibition also reduced the spike-associated [Ca2+]i changes in the distal dendrites but had little effect on the changes in the proximal part of the cell. Both of these results are consistent with inhibition converting actively backpropagating spikes into passively spreading potentials at some point in the arbor. 3. In most cells, the spike amplitude reduction in the distal dendrites was blocked by bicuculline methiodide (10 microM) and inhibition was most effective when evoked in a time window < 10 ms preceding the action potential. This suggests that the amplitude reduction was due to a conductance shunt activated by gamma-aminobuturic acid-A (GABAA) receptors. Synaptically evoked GABAB responses were detected but usually did not block spike propagation. 4. Direct hyperpolarization in the distal dendrites was also effective in blocking antidromically evoked spike backpropagation but probably does not contribute when the action potentials are evoked synaptically. 5. This effect of inhibition is different from its usual function in synaptic integration because spike generation and propagation down the axon are not significantly affected. This kind of inhibition might be important in regulating transient [Ca2+]i changes in the dendrites including individual dendritic branches.

Animals↗

PubMed2004

Derivation and analysis of basic computational operations of thalamocortical circuits.

Shared anatomical and physiological features of primary, secondary, tertiary, polysensory, and associational neocortical areas are used to formulate a novel extended hypothesis of thalamocortical circuit operation. A simplified anatomically based model of topographically and nontopographically projecting ("core" and "matrix") thalamic nuclei, and their differential connections with superficial, middle, and deep neocortical laminae, is described. Synapses in the model are activated and potentiated according to physiologically based rules. Features incorporated into the models include differential time courses of excitatory versus inhibitory postsynaptic potentials, differential axonal arborization of pyramidal cells versus interneurons, and different laminar afferent and projection patterns. Observation of the model's responses to static and time-varying inputs indicates that topographic "core" circuits operate to organize stored memories into natural similarity-based hierarchies, whereas diffuse "matrix" circuits give rise to efficient storage of time-varying input into retrievable sequence chains. Examination of these operations shows their relationships with well-studied algorithms for related functions, including categorization via hierarchical clustering, and sequential storage via hash- or scatter-storage. Analysis demonstrates that the derived thalamocortical algorithms exhibit desirable efficiency, scaling, and space and time cost characteristics. Implications of the hypotheses for central issues of perceptual reaction times and memory capacity are discussed. It is conjectured that the derived functions are fundamental building blocks recurrent throughout the neocortex, which, through combination, gives rise to powerful perceptual, motor, and cognitive mechanisms.

Algorithms↗

PubMed1999

Noradrenergic synaptic transmission in the superior cervical ganglion.

Morphology of dendrites of principal neurons in the rat superior cervical ganglion (SCG) was re-examined by an intracellular staining method followed by electron microscopic analysis. They exhibit a varying complexity in their morphology and arborization. Some dendrites show specializations such as a glomerular plexus, where extensively branched dendritic collaterals form synaptic connections comprising not only axodendritic synapses between preganglionic axons and principal cell dendrites, but also dendrodendritic synapses between principal cell dendrites. Most presynaptic elements of adrenergic synapses observed by conventional methods appear to represent these specialized dendritic collaterals of principal neurons. In denervated SCG, focal stimulation revoked an inhibitory postsynaptic potential in some principal neurons. The response was completely blocked by yohimbine, an alpha 2-adrenoceptor antagonist. The inhibitory synaptic connection between principal neurons via dendrodendritic synapses may be an important addition to the conventional scheme of intraganglionic synaptic transmission. Sympathetic ganglia may thus function as more than a simple relay station, with specialized neuronal circuitry that may be involved in the modulation of cholinergic transmission.

Adrenergic alpha-Antagonists↗

PubMed1994

Age-dependent long-term potentiation of inhibitory synaptic transmission in rat visual cortex.

Long-term potentiation (LTP) of inhibitory synaptic transmission in rat visual cortex was investigated using intracellular recording in slice preparations. The inhibitory postsynaptic potential (IPSP) of layer V cells evoked monosynaptically by layer IV stimulation was recorded while excitatory postsynaptic potentials (EPSPs) were blocked by adding NMDA and non-NMDA receptor antagonists to the perfusate. Separate presynaptic fiber groups were activated by two stimulating electrodes placed in layer IV. One electrode was used to test the effect of conditioning stimulation; the other served as a control. Trains of high-frequency stimulation (50 Hz, 1 sec) were applied at an interval of 10 sec as a conditioning stimulation. The LTP of IPSP induced by the conditioning stimulation had properties similar to those known for LTP of EPSP in hippocampal CA1: (1) it was specific to the conditioned pathway; (2) repetitive application of the conditioning stimulation saturated the LTP; (3) LTP was induced by conditioning stimulation at intensities higher than a threshold; (4) weak conditioning stimulation to one pathway, which alone failed to induce LTP, induced associative LTP when strong conditioning stimulation was simultaneously applied to the other pathway; (5) weak conditioning stimulation sometimes induced short-term potentiation. In contrast to these similarities, LTP of IPSP was induced by a wider range of stimulus frequencies than that capable of generating LTP of EPSPs in CA1. It was induced not only by a brief high-frequency stimulation but also by an intermediate-frequency (2 Hz) stimulation continued for 5 min. In addition, the LTP induction was not dependent on postsynaptic membrane potential. Finally, the LTP of IPSP was more easily induced in developing than in mature rats. This age dependence suggests that LTP of IPSPs may contribute to the improvement of response selectivity of visual cortical cells through visual experience during postnatal development.

Aging↗

PubMed1990

Neurotransmitter receptors mediating excitatory input to cells in the cat lateral geniculate nucleus. I. Lagged cells.

1. Synaptic mechanisms that might explain the functional properties of the recently discovered class of lagged cells in the dorsal lateral geniculate nucleus (LGN) were analyzed with electrophysiological and pharmacologic techniques. To study the type of excitatory amino acid (EAA) receptor that mediates visual responses of lagged cells, we recorded the response of single cells to a stationary flashing light spot before, during, and after microiontophoretic application of antagonists and agonists to EAA receptors. 2. The visual response of the lagged cells could be almost completely blocked by an antagonist to the N-methyl-D-aspartate (NMDA) receptor. The degree of suppression was dose dependent, and the average maximum degree of suppression for all the cells was 94%. NMDA enhanced the response, and this enhancement was antagonized by NMDA antagonists. A quisqualate/kainate receptor antagonist had no significant effect on the lagged cells. 3. These findings indicate that the visual response in lagged cells is dependent upon activation of NMDA receptors, which may directly result from activation of retinal inputs. 4. No pharmacologic difference was seen between lagged X- and Y-cells, or between lagged ON- and OFF-center cells. 5. gamma-Aminobutyric acid-A (GABA-A) receptor antagonists were used to study whether the characteristic lag of the visual response and the suppression of the initial transient response component of the lagged cells are dependent on geniculate inhibition. Beside enhancement of the visual response, the GABA antagonists strongly reduced the lag of the visual response, and an initial transient response component occurred instead of the initial suppression. The lag remained slightly longer than for nonlagged cells, and the peak firing rate of the transient was below values typical for nonlagged cells, indicating that the lagged cell properties are dependent on other factors beside GABA-A receptor-mediated inhibition. 6. The enhanced visual response during iontophoresis of GABA antagonists could be completely blocked by simultaneous iontophoresis of an NMDA-receptor antagonist. This gives further support to the hypothesis that the retinal input to these cells is mediated by NMDA receptors. 7. The NMDA-receptor/ionophore complex mediates excitatory postsynaptic potentials (EPSPs) characterized by slow rise and decay times and long duration. The ionophore is characterized by a voltage-dependent blockade that makes these receptors particularly sensitive to inhibitory input. The temporal interplay between the slow NMDA receptor-mediated EPSPs and the fast GABA receptor-mediated inhibitory postsynaptic potentials (IPSPs) may explain the characteristic response properties of the lagged cells.

Afferent Pathways↗

PubMed2002

Physiological properties of late inspiratory neurons and their possible involvement in inspiratory off-switching in cats.

To assess the functional significance of late inspiratory (late-I) neurons in inspiratory off-switching (IOS), membrane potential and discharge properties were examined in vagotomized, decerebrate cats. During spontaneous IOS, late-I neurons displayed large membrane depolarization and associated discharge of action potentials that started in late inspiration, peaked at the end of inspiration, and ended during postinspiration. Depolarization was decreased by iontophoresis of dizocilpine and eliminated by tetrodotoxin. Stimulation of the vagus nerve or the nucleus parabrachialis medialis (NPBM) also evoked depolarization of late-I neurons and IOS. Waves of spontaneous chloride-dependent inhibitory postsynaptic potentials (IPSPs) preceded membrane depolarization during early inspiration and followed during postinspiration and stage 2 expiration of the respiratory cycle. Iontophoresed bicuculline depressed the IPSPs. Intravenous dizocilpine caused a greatly prolonged inspiratory discharge of the phrenic nerve (apneusis) and suppressed late-inspiratory depolarization as well as early-inspiratory IPSPs, resulting in a small constant depolarization throughout the apneusis. NPBM or vagal stimulation after dizocilpine produced small, stimulus-locked excitatory postsynaptic potentials (EPSPs) in late-I neurons. Neurobiotin-labeled late-I neurons revealed immunoreactivity for glutamic acid decarboxylase as well as N-methyl-D-aspartate (NMDA) receptors. These results suggest that late-I neurons are GABAergic inhibitory neurons, while the effects of bicuculline and dizocilpine indicate that they receive periodic waves of GABAergic IPSPs and glutamatergic EPSPs. The data lead to the conclusion that late-I neurons play an important inhibitory role in IOS. NMDA receptors are assumed to augment and/or synchronize late-inspiratory depolarization and discharge of late-I neurons, leading to GABA release and consequently off-switching of bulbar inspiratory neurons and phrenic motoneurons.

Action Potentials↗

PubMed1995

An identified glutamatergic interneuron patterns feeding motor activity via both excitation and inhibition.

1. Previously we demonstrated that glutamate is an important neurotransmitter in the CNS of Helisoma. Exogenous glutamate applied to the buccal ganglia mimicked both the excitatory and inhibitory effects of subunit 2 (S2) of the tripartite central pattern generator (CPG) on S2 postsynaptic motor neurons. Here we identify buccal interneuron B2 as an S2 interneuron by utilizing a combination of electrophysiology, pharmacology, and intracellular staining. In addition, neurons that were electrophysiologically and morphologically characterized as neuron B2 demonstrated antiglutamate immunoreactivity, suggesting that neuron B2 is a source of endogenous glutamate in the buccal ganglia. 2. Depolarization of neuron B2 evoked excitatory postsynaptic potentials in motor neurons excited by S2. The excitatory effects of B2 depolarization and S2 activation were reversibly antagonized by the ionotropic glutamate receptor antagonist 6-cyano-7-nitro-quinoxaline-2,3-dione, similar to the antagonism shown previously for application of exogenous glutamate. Depolarization of neuron B2 also evoked inhibitory postsynaptic potentials in motor neurons inhibited by S2. When such motor neurons were maintained in isolated cell culture, application of exogenous glutamate produced a direct hyperpolarization of the membrane potential. 3. The activity of neuron B2 is necessary for the production of the standard pattern of buccal motor neuron activity, which underlies functional feeding movements. The subunits of the tripartite buccal CPG must be active in the temporal sequence S1-S2-S3 to produce the standard feeding pattern. Rhythmic inhibition from neuron B2 terminated activity in S1 postsynaptic motor neurons and entrained the frequency of activity in S3 postsynaptic motor neurons. Hyperpolarization of neuron B2 disrupted the production of the standard motor pattern by eliminating S2 postsynaptic potentials in identified buccal motor neurons, thereby prolonging S1 activity and disrupting S3 bursting. 4. These data support the hypothesis that S2 neuron B2 is glutamatergic and demonstrate that glutamatergic transmission, and especially inhibition, is fundamental to the production of behaviorally critical motor neuron activity patterns in Helisoma.

6-Cyano-7-nitroquinoxaline-2,3-dione↗

PubMed1996

Convergent carotid sinus nerve and superior laryngeal nerve afferent inputs to neurons in the NTS.

A population of 43 neurons in the nucleus of the solitary tract (NTS) was identified in pentobarbital sodium anesthetized, paralyzed, and artificially ventilated cats that received convergent inputs from carotid sinus nerve (CSN) and superior laryngeal nerve (SLN) afferents. In 21 neurons, electrical stimulation of the CSN and SLN each evoked an excitatory postsynaptic potential (EPSP; mean onset latency +/- SE of CSN-evoked input = 7.2 +/- 0.8 ms, range 2.1-14.1 ms; of SLN-evoked input = 10.3 +/- 2.1 ms, range 2.8-46.8 ms). In 22 neurons, electrical stimulation of either the CSN or SLN evoked an EPSP/ inhibitory postsynaptic potential (IPSP) sequence (CSN-evoked input = 6.7 +/- 0.6 ms, range 2.1-12.2 ms; SLN-evoked input = 8.4 +/- 0.8 ms, range 3.0-19.4 ms). Spatial interactions (facilitation, summation, occlusion) and time-dependent inhibitory interactions were observed between the convergent inputs. Natural stimulation of specific receptors indicated that 14 cells received a convergent excitatory input from carotid sinus baroreceptors and laryngeal mechanoreceptors, 10 received a convergent excitatory input from carotid body chemoreceptors and laryngeal mechanoreceptors, and 5 received a convergent excitatory input from baroreceptors, chemoreceptors, and laryngeal mechanoreceptors. The interactions and various patterns of convergence suggest a significant integration of convergent inputs from disparate afferent sources by these neurons.

Afferent Pathways↗

PubMed2001

Reorganisation of respiratory network activity after loss of glycinergic inhibition.

gamma-Aminobutyric acid (GABA)-ergic and glycinergic inhibition is believed to play a major role in the respiratory network. In the present study we tested whether specific blockade of glycinergic inhibition resulted in changes in respiratory network interaction and function. Using the working heart-brainstem preparation from adult mice, we recorded phrenic nerve activity and the activity of different types of respiratory neurones located in the ventrolateral medulla. Strychnine (0.03-0.3 microM) was given systemically to block glycine receptors (Gly-R). During exposure to strychnine, post-inspiratory (PI) neurones shifted their onset of discharge into the inspiratory phase. As a consequence, the post-inspiratory phase failed and the rhythm changed from a three-phase cycle (inspiration, post-inspiration, expiration, with a frequency of about. 0.24 Hz) to a faster, two-phased cycle (inspiration expiration, frequency about 0.41 Hz). Inspiratory and expiratory neurones altered their augmenting membrane potential pattern to a rapidly peaking pattern. Smaller voltage oscillations at approximately 10 Hz and consisting of excitatory and inhibitory postsynaptic potential sequences occurred during the expiratory interval. Due to their high frequency and low amplitude, such oscillations would be inadequate for lung ventilation. We conclude that, under physiological conditions, glycinergic inhibition does indeed play a major role in the generation of a normal respiratory rhythm in adult mice. After failure of glycinergic inhibition a faster respiratory rhythm seems to operate through reciprocal GABAergic inhibition between inspiratory and expiratory neurones, while phase switching is organised by activation of intrinsic membrane properties.

Animals↗