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PubMed1999

Modulation of cholinergic transmission in the neuronal network of the gill and siphon withdrawal reflex in Aplysia.

Inhibitory interneurons are important elements of the network underlying the gill and siphon withdrawal reflex in Aplysia, and a large component of this inhibition is cholinergic. In this study, we investigated one key identified cholinergic inhibitory interneuron of the network, neuron L16, and studied some properties of its synaptic transmission and its modulation. We found that a slow inhibitory postsynaptic potential evoked in sensory neurons by L16 has two components. An earlier inhibitory postsynaptic potential component is sensitive to curare (100 microM) and has a reversal potential near the Cl- equilibrium potential (-54.5 mV). A later inhibitory postsynaptic potential component is sensitive to tetraethylammonium (0.5-1 mM); it is decreased by membrane hyperpolarization and becomes undetectable near the K+ equilibrium potential (between -80 and -90 mV). Input to sensory neurons from L16 can be altered by two neuromodulators of the reflex, the small cardioactive peptide and serotonin. Small cardioactive peptide (10 microM) facilitates the connections between L16 and the sensory neurons, while serotonin (5-10 microM) inhibits them. Part of the effect of serotonin on the transmission between L16 and the sensory neurons is due to a postsynaptic mechanism, since responses to acetylcholine application in these cells are decreased by serotonin. These results indicate an additional site of synaptic plasticity in the withdrawal reflex network, the inhibitory cholinergic transmission, by two major neuromodulatory transmitters, small cardioactive peptide and serotonin.

Action Potentials↗

PubMed1967

Opposite synaptic actions mediated by different branches of an identifiable interneuron in Aplysia.

Among the identifiable cells in the abdominal ganglion of Aplysia californica are five that generate bursting rhythms endogenous to the cells. In the four bursting cells of the left upper quadrant the rhythm is modulated by a unitary inhibitory postsynaptic potential; in the bursting cell of the right lower quadrant the rhythm is modulated by a unitary excitatory postsynaptic potential. Both the excitatory and inhibitory postsynaptic potentials are mediated by separate branches of a single interneuron. The pharmacological properties of the double action interneuron as well as those of the follower cells suggest that a single transmitter (acetylcholine) is involved in both the excitatory and the in-hibitory action of the interneuron.

Acetylcholine↗

PubMed1995

Characterization of synaptic connections between cortex and deep nuclei of the rat cerebellum in vitro.

Intracellular recordings were used to characterize the inhibitory synapses formed by Purkinje cells on neurons in the deep cerebellar nuclei of the rat. This work was performed on organotypic cerebellar cultures where functional connections between Purkinje cells and deep cerebellar neurons are formed de novo. After blocking ionotropic excitatory amino acid, and GABAA receptors with 6-cyano-7-nitro-quinoxaline-2,3-dione,D-2-amino-5-phosphonovalerate and bicuculline, respectively, the majority of deep cerebellar neurons fired spontaneously without accommodation. This tonic firing was linearly dependent on membrane potential and was abolished with hyperpolarization. Bath application of muscimol and baclofen reversibly hyperpolarized deep cerebellar nuclei cells. In the presence of excitatory amino acid receptor antagonists, field stimulation within the Purkinje cell layer induced monosynaptic inhibitory potentials in deep cerebellar neurons that were graded and completely blocked by bicuculline. Inhibitory potential amplitudes were not markedly reduced during fast repetitive stimulation of Purkinje cells, and the resulting hyperpolarization was not affected by the competitive GABAB receptor antagonist CGP 35348. A single inhibitory potential temporarily interrupted trains of action potentials induced in deep cerebellar cells by short depolarizing pulses. Trains of five inhibitory postsynaptic potentials, evoked at 20 Hz, induced a hyperpolarization which transiently blocked the spontaneous firing of deep cerebellar cells. The efficiency to block action potential discharges depended on the frequency of evoked inhibitory potentials. Bath application of bicuculline induced burst discharges in the control solution. When the excitatory amino acid receptors were pharmacologically blocked, bicuculline depolarized deep cerebellar neurons inducing sustained action potential discharges. In the presence of tetrodotoxin, bicuculline abolished miniature inhibitory postsynaptic potentials and resulted in a membrane depolarization of deep cerebellar cells. We conclude that deep cerebellar neurons isolated from synaptic inputs display a pacemaker-like activity. Although these neurons possess GABAA and GABAB receptors, we confirm that only GABAA receptors were involved in the generation of inhibitory postsynaptic potentials, even with high frequency stimulation. The amplitude of evoked inhibitory potentials was weakly frequency-dependent, thus allowing a powerful inhibition of the pacemaker-like activity by trains of evoked inhibitory postsynaptic potentials. Additionally, spontaneous and miniature inhibitory potentials control the excitability of deep cerebellar neurons by exerting a continuous hyperpolarizing tone.

2-Amino-5-phosphonovalerate↗

PubMed1999

The GABA(B) receptor antagonist CGP 55845A reduces presynaptic GABA(B) actions in neocortical neurons of the rat in vitro.

Use-dependent depression of inhibitory postsynaptic potentials was investigated with intracellular recordings and the paired-pulse paradigm in rat neocortical neurons in vitro. Pairs of stimuli invariably reduced the second inhibitory postsynaptic potential-A (GABA(A) receptor-mediated inhibitory postsynaptic potential) of a pair; at interstimulus intervals of 500 ms, the amplitude of the second inhibitory postsynaptic potential-A was considerably smaller than the first (36.2 +/- 6.2%, n= 17). Decreasing the interstimulus interval reduced the second inhibitory postsynaptic potential-A further and with interstimulus intervals shorter than 330 ms the compound excitatory postsynaptic potential-inhibitory postsynaptic potential response reversed from a hyperpolarizing to a depolarizing response. The depression of the inhibitory postsynaptic potential-A exhibited a maximum at interstimulus intervals near 150 ms and recovered with a time constant of 282 +/- 96.2 ms. Elimination of excitatory transmission by the application of 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX) and D(-)-2-amino-5-phosphonovaleric acid yielded an essentially unaltered time-course of paired-pulse depression (maximum depression near 150 ms, time constant of recovery 232 +/- 98 ms). The polarity change of the compound excitatory postsynaptic potential response at shorter interstimulus intervals was abolished in the presence of CNQX and D(- )-2-amino-5-phosphonovaleric acid. CNQX and D(-)-2-amino-5-phosphonovaleric acid also reduced the apparent depolarizing shift of the reversal potential between the first and second inhibitory postsynaptic potential-A from about 6 mV to less than 2 mV. Application of the GABA(B) receptor antagonist CGP 55845A in the presence of CNQX and (-)-2-amino-5-phosphonovaleric acid abolished the inhibitory postsynaptic potential-B and paired-pulse depression. Under these conditions, the amplitude of the second inhibitory postsynaptic potential was, on average, about 90% of the first, i.e. reduced by about 10%. The second inhibitory postsynaptic potential-A was approximately constant at interstimulus intervals between 100 and 500 ms. It is concluded that paired-pulse depression of cortical inhibition is predominantly mediated by presynaptic GABA(B) receptors of GABAergic interneurons. The abolition of net inhibition at interstimulus intervals near 330 ms may facilitate spread of excitation and neuronal synchrony during repetitive cortical activation near 3 Hz. This use-dependent depression of inhibition may contribute to highly synchronized slow electroencephalogram activity during spike-and-wave or delta activity.

2-Amino-5-phosphonovalerate↗

PubMed1986

Effect of stimulation of the nucleus reticularis gigantocellularis on the membrane potential of cat lumbar motoneurons during sleep and wakefulness.

The present study was performed in order to determine the effect of electrical stimulation of the medullary nucleus reticularis gigantocellularis (NRGc) on the membrane potential of spinal cord motoneurons during sleep and wakefulness. Accordingly, intracellular recordings were obtained from lumbar motoneurons in unanesthetized normally respiring cats during naturally occurring states of wakefulness, quiet sleep and active sleep. Electrical stimuli applied to the NRGc evoked synaptic potentials which occurred at short latency (less than 10 ms) and did not exhibit consistent changes in their waveforms during any states of sleep or wakefulness. During wakefulness and quiet sleep, longer latency (greater than 20 ms) low-amplitude hyperpolarizing potentials occasionally followed NRGc stimulation. However, during active sleep, NRGc stimulation produced, in all motoneurons, relatively large hyperpolarizing potentials that were characterized by a mean amplitude of 3.5 +/- 0.4 mV (mean +/- S.E.M.), a mean latency-to-peak of 43.0 +/- 0.8 ms, and an average duration of 34.4 +/- 1.7 ms. These potentials were capable of blocking the generation of orthodromic spikes elicited by sciatic nerve stimulation. When anodal current or chloride was passed through the recording electrode, the hyperpolarizing potentials decreased in amplitude, and in some cases their polarity was reversed. These results indicate that the active sleep-specific hyperpolarizing potentials were inhibitory postsynaptic potentials. Thus, the NRGc possesses the capability of providing a postsynaptic inhibitory drive that is directed toward lumbar motoneurons which is dependent on the occurrence of the behavioral state of active sleep.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1999

Inhibition of styloglossus motoneurons during the palatally induced jaw-closing reflex.

The inhibition of hypoglossal motoneurons innervating the styloglossus muscle during transient jaw closing, the so-called jaw-closing reflex, was studied in cats. The application of diffuse pressure stimulation to the posterior palatal surface produced the jaw-closing reflex and inhibitory postsynaptic potentials in the styloglossus motoneurons, indicating that mechanosensory inputs from the posterior palatal mucosa sent inhibitory synaptic inputs to styloglossus motoneurons. We also demonstrated that, during the palatally induced jaw-closing reflex, the tongue extended at jaw closure and was still extended forward in the initial part of the opening phase. In all of 22 styloglossus motoneurons studied, the depression of firing was elicited after the onset of jaw closure. In 14 of 22 styloglossus motoneurons, the depression of firing was elicited in the closing phase, and in the remaining cells it was elicited in the occlusal phase. By increasing the intracellular concentration of chloride ions, the inhibitory postsynaptic potential elicited in the styloglossus motoneuron converted to a depolarizing potential. It is concluded that the inhibition of styloglossus motoneurons may be involved in the maintenance of tongue protrusions during the palatally induced jaw-closing reflex, and that inhibitory postsynaptic potentials evoked in the styloglossus motoneurons are partly due to a chloride-dependent inhibitory postsynaptic potential.

Animals↗

PubMed2002

Tetanus toxin induces long-term changes in excitation and inhibition in the rat hippocampal CA1 area.

Intrahippocampal tetanus toxin induces a period of chronic recurrent limbic seizures in adult rats, associated with a failure of inhibition in the hippocampus. The rats normally gain remission from their seizures after 6-8 weeks, but show persistent cognitive impairment. In this study we assessed which changes in cellular and network properties could account for the enduring changes in this model, using intracellular and extracellular field recordings in hippocampal slices from rats injected with tetanus toxin or vehicle, 5 months previously. In CA1 pyramidal neurones from toxin-injected rats, the slope of the action potential upstroke was reduced by 32%, the fast afterhyperpolarisation by 32% and the slow afterhyperpolarisation by 54%, suggesting changes in voltage-dependent conductances. The excitatory postsynaptic potential slope was reduced by 60% and the population synaptic potential slope was reduced at all stimulus intensities, suggesting a reduced afferent input in CA1. Paired-pulse stimulation showed an increase of the excitability ratio and an increase of cellular excitability only for the second pulse, suggesting a reduced inhibition. The polysynaptic inhibitory postsynaptic potential was reduced by 34%, whereas neither the inhibitory postsynaptic potential at subthreshold stimulus intensities,nor the pharmacologically isolated monosynaptic inhibitory postsynaptic potential were different in toxin-injected rats, suggesting a reduced synaptic excitation of interneurones. Stratum radiatum stimuli in toxin-injected rats, and not in controls, evoked antidromic activation of CA1 neurones, demonstrating axonal sprouting into areas normally devoid of CA1 pyramidal cell axons.We conclude that this combination of enduring changes in cellular and network properties, both pro-epileptic (increased recurrent excitatory connectivity, reduced recurrent inhibition and reduced afterhyperpolarisations) and anti-epileptic (impaired firing and reduced excitation), reaches a balance that allows remission of seizures, perhaps at the price of persistent cognitive impairment.

Action Potentials↗

PubMed1991

Inhibition of caudal medullary expiratory neurones by retrofacial inspiratory neurones in the cat.

1. Comparisons between the spike discharge of inspiratory neurons within the retrofacial area (RFN), and the membrane potential of expiratory neurones within the caudal medulla were made in pentobarbitone-anaesthetized, vagotomized, artificially ventilated cats. Spike-triggered averaging (STA) of synaptic potentials, triggered by the discharge of inspiratory RFN neurones, was utilized to test for synaptic connectivity. 2. Eighty-nine neurons with respiratory-phased discharge patterns were recorded in the vicinity of the RFN. Fifty-four neurones discharged at or slightly before the onset of the inspiratory burst activity of the phrenic nerve and continued firing throughout inspiration. Two continued to fire during post-inspiration. Forty-five of fifty-four inspiratory RFN neurones exhibited incrementing discharge patterns, six discharged with a plateau pattern, while only three neurones had a decrementing discharge pattern. 3. The membrane potential trajectories of caudal expiratory neurones revealed a typical wave of early inspiratory hyperpolarization. Occasionally, a second wave of hyperpolarization occurred during late inspiration, in conjunction with increased phrenic nerve activity. 4. Spike-triggered averaging revealed averaged inhibitory postsynaptic potentials (IPSPs), indicative of inhibitory synaptic connections, between eight and sixty-three pairs of RFN inspiratory and caudal expiratory neurones. 5. Inhibitory postsynaptic potentials detected by STA exhibited a relatively long latency and a slow time course. The IPSPs began, on average, 3.8 ms after an RFN action potential. The rise times, half-widths and durations of IPSPs were longer than expected for a monosynaptic somal input from myelinated axons of inspiratory RFN neurones. It is suggested that an inhibitory relay neurone in the immediate vicinity of the expiratory neurones is activated by a collateral of the RFN inspiratory neurone. 6. Retrofacial inspiratory neurones were antidromically activated only when high-intensity electrical stimulation was applied in the vicinity of caudal expiratory neurones. 7. The averaged IPSPs were preceded by diphasic and triphasic 'spike potentials'. The averaged spike potentials were highly entrained to the action potentials of RFN inspiratory neurones which triggered IPSPs. The spike potentials may be terminal potentials recorded from axons of RFN inspiratory neurones. 8. Evidence for convergence of synaptic inputs was obtained from STA tests in a caudal expiratory neurone receiving IPSPs from four RFN neurones. 9. The functional significance of this observation is discussed. We conclude that RFN inspiratory neurones exert a moderate inhibitory influence and act conjointly with other types of medullary inspiratory neurones.

Animals↗

PubMed1995

In vitro study of afferent synaptic transmission in the rostral gustatory zone of the rat nucleus of the solitary tract.

The synaptic responses of rostral nucleus of the solitary tract (rNST) neurons to electrical stimulation of the solitary tract (ST) fibers were investigated using whole-cell recordings in brain slices of adult rat medulla. Most neurons of the rNST (47%) responded to stimulation of the ST with excitatory postsynaptic potentials (EPSPs), 28% responded with mixed excitatory and inhibitory postsynaptic potentials (PSPs) and 25% responded with inhibitory postsynaptic potentials (IPSPs). The estimated reversal potentials for the EPSPs (EEPSP) was -7 mV and for the IPSPs (EIPSP) was -69 mV. The glutamate antagonist 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX) acting at the alpha-amino-3-hydroxy-5-methyl-isoxazole-4-propionic acid (AMPA)/kainate receptor, either reduced or blocked all EPSPs tested. D-2-Amino-5-phosphonovalerate (APV), a selective N-methyl-D-aspartate (NMDA) receptor antagonist, also reduced the amplitude of the EPSPs. These results suggest that glutamate is released following stimulation of afferent fibers in the ST and acts on both AMPA/kainate and NMDA glutamate receptors. The IPSPs result from release of gamma-aminobutyric acid (GABA) since superfusion of the GABAA receptor antagonist, bicuculline reversibly blocked the IPSPs. The GABAB receptor antagonist, phaclofen, also reduced the IPSP components in some neurons, indicating that both GABAA and GABAB receptors are involved in inhibitory transmission in the rNST. When the morphology of the recorded neurons was examined by filling the neurons with biocytin and reconstructing the neurons, each morphological type of rNST neuron responded with excitatory and inhibitory PSPs following stimulation of the ST.

6-Cyano-7-nitroquinoxaline-2,3-dione↗

PubMed1989

Muscarinic excitation and inhibition of neurons in the submucous plexus of the guinea-pig caecum.

Intracellular recordings were made from neurons in the submucous plexus of the guinea-pig caecum. Muscarinic agonists (acetylcholine, bethanechol and muscarine) depolarized about 70%, and hyperpolarized about 30% of the submucous plexus neurons. Low concentrations of pirenzepine reversibly antagonized both responses. The measured dissociation constants (KD) of 10-30 nM for the depolarizations and 1-3 nM for the hyperpolarizations suggest that each response was mediated by muscarinic M1 cholinoceptors. The muscarinic depolarization and hyperpolarization were associated with a decreased and an increased conductance, respectively, and the reversal potential for the muscarinic responses varied as the potassium concentration varied, always being around the potassium equilibrium potential. In cells depolarized by muscarinic agonists these agents appeared to decrease a potassium conductance that could also be inactivated by substance P. In approximately 30% of the submucous neurons, the slow inhibitory postsynaptic potential, elicited in response to single or repetitive focal stimuli (1-10 pulses at 20-40 Hz), appeared to consist of a large component which was sensitive to the blocking action of idazoxan (100-300 nM) and a small component which was idazoxan-insensitive. The latter (muscarinic slow inhibitory postsynaptic potential) was completely abolished by pirenzepine. The concentrations of pirenzepine which caused a 50% depression ranged from 5 to 20 nM. The muscarinic slow inhibitory postsynaptic potential was increased in amplitude and duration by physostigmine (100-300 nM). The muscarinic slow inhibitory postsynaptic potential was accompanied by a decrease in membrane input resistance, and was reversed in polarity near the potassium equilibrium potential. When muscarine induced a hyperpolarization and/or focal stimulation elicited a muscarinic slow inhibitory postsynaptic potential in the presence of idazoxan (100-300 nM), the intracellular injection of guanosine 5'-O-(3-thiotriphosphate) produced a progressive membrane hyperpolarization during which the muscarinic hyperpolarizing responses were attenuated. It is concluded that the muscarine-induced reduction in potassium conductance is mediated through a muscarinic M1 receptor which has a relatively low affinity for pirenzepine. The muscarine-induced increase in potassium conductance is probably produced by the association of a guanine nucleotide-binding regulatory protein with another muscarinic M1 receptor that has a relatively high affinity for pirenzepine.

Acetylcholine↗

PubMed1996

Gamma-aminobutyric acid type B receptor-dependent burst-firing in thalamic neurons: a dynamic clamp study.

Synchronized network responses in thalamus depend on phasic inhibition originating in the thalamic reticular nucleus (nRt) and are mediated by the neurotransmitter gamma-aminobutyric acid (GABA). A suggested role for intra-nRt connectivity in inhibitory phasing remains controversial. Recently, functional GABA type B (GABAB) receptors were demonstrated on nRt cells, and the slow time course of the GABAB synaptic response seems ideally suited to deinactivate low-threshold calcium channels. This promotes burst firing, a characteristic feature of synchronized responses. Here we investigate GABAB-mediated rebound burst firing in thalamic cells. Whole-cell current-clamp recordings were obtained from nRt cells and somatosensory thalamocortical relay cells in rat brain slices. Synthetic GABAB inhibitory postsynaptic potentials, generated by a hybrid computerneuron synapse (dynamic clamp), triggered rebound low-threshold calcium spikes in both cell types when peak inhibitory postsynaptic potential hyperpolarization was greater than -92 mV. The threshold inhibitory postsynaptic potential conductance for rebound burst generation was comparable in nRt (7 nS) and thalamocortical (5 nS) cells. However, burst onset in nRt (1 s) was considerably delayed compared with thalamocortical (0.6 s) cells. Thus, GABAB inhibitory postsynaptic potentials can elicit low-threshold calcium spikes in both relay and nRt neurons, but the resultant oscillation frequency would be faster for thalamocortical-nRt networks (3 Hz) than for nRt-nRt networks (1-2 Hz). We conclude, therefore, that fast (> 2 Hz) GABAB-dependent thalamic oscillations are maintained primarily by reciprocal connections between excitatory and inhibitory cells. These findings further indicate that when oscillatory neural networks contain both recurrent and reciprocal inhibition, then distinct population frequencies may result when one or the other type of inhibition is favored.

Animals↗

PubMed1997

Shortened-duration GABA(A) receptor-mediated synaptic potentials underlie enhanced CA1 excitability in a chronic model of temporal lobe epilepsy.

Intracellular recording techniques were used to examine GABA(A) receptor-mediated synaptic inhibition in pyramidal cells of the CA1 region of the rat hippocampus in the post-self sustaining limbic status epilepticus model of temporal lobe epilepsy. Orthodromically evoked, monosynaptic inhibitory postsynaptic potentials were recorded in vitro following pharmacological blockade of ionotropic glutamate and GABA(B) receptors. Inhibitory postsynaptic potentials from epileptic tissue were kinetically altered relative to controls; both the 10-90% rise-time and width (measured at half-maximum amplitude) were reduced by approximately 50% resulting in significant shortening of duration. The degree of pyramidal cell hyperexcitability, assessed before pharmacological treatment as the number of action potentials evoked by maximum intensity afferent stimulation, correlated significantly with the magnitude of synaptic potential duration reduction determined following blockade of glutamatergic neurotransmission. Bath application of the benzodiazepine type 1 receptor agonist zolpidem reduced post-self sustaining limbic status epilepticus CA1 pyramidal cell hyperexcitability substantially (but not completely) via a marked increase in inhibitory postsynaptic potential area. Post-self-sustaining limbic status epilepticus inhibitory postsynaptic potentials which exhibited the most pronounced shortening were augmented by zolpidem to a greater degree than longer duration synaptic potentials. In contrast, zolpidem-induced augmentation of control inhibitor, postsynaptic potential area was much less robust. It is suggested that a deficiency in post-self-sustaining limbic status epilepticus GABA(A) receptor-mediated synaptic inhibition contributes to a state of partial disinhibition which is a major factor in enhanced CA1 excitability in chronic limbic epilepsy. Possible mechanisms underlying post-self-sustaining limbic status epilepticus kinetic abnormalities are discussed.

2-Amino-5-phosphonovalerate↗

PubMed2006

Stimulation of adenosine A1 and A2A receptors by AMP in the submucosal plexus of guinea pig small intestine.

Actions of adenosine 5'-monophosphate (AMP) on electrical and synaptic behavior of submucosal neurons in guinea pig small intestine were studied with "sharp" intracellular microelectrodes. Application of AMP (0.3-100 microM) evoked slowly activating depolarizing responses associated with increased excitability in 80.5% of the neurons. The responses were concentration dependent with an EC(50) of 3.5 +/- 0.5 microM. They were abolished by the adenosine A(2A) receptor antagonist ZM-241385 but not by pyridoxal-phosphate-6-azophenyl-2,4-disulfonic acid, trinitrophenyl-ATP, 8-cyclopentyl-1,3-dimethylxanthine, suramin, or MRS-12201220. The AMP-evoked responses were insensitive to AACOCF3 or ryanodine. They were reduced significantly by 1) U-73122, which is a phospholipase C inhibitor; 2) cyclopiazonic acid, which blocks the Ca(2+) pump in intraneuronal membranes; and 3) 2-aminoethoxy-diphenylborane, which is an inositol (1,4,5)-trisphosphate receptor antagonist. Inhibitors of PKC or calmodulin-dependent protein kinase also suppressed the AMP-evoked excitatory responses. Exposure to AMP suppressed fast nicotinic ionotropic postsynaptic potentials, slow metabotropic excitatory postsynaptic potentials, and slow noradrenergic inhibitory postsynaptic potentials in the submucosal plexus. Inhibition of each form of synaptic transmission reflected action at presynaptic inhibitory adenosine A(1) receptors. Slow excitatory postsynaptic potentials, which were mediated by the release of ATP and stimulation of P2Y(1) purinergic receptors in the submucosal plexus, were not suppressed by AMP. The results suggest an excitatory action of AMP at adenosine A(2A) receptors on neuronal cell bodies and presynaptic inhibitory actions mediated by adenosine A(1) receptors for most forms of neurotransmission in the submucosal plexus, with the exception of slow excitatory purinergic transmission mediated by the P2Y(1) receptor subtype.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗

PubMed1993

Electrophysiological identification of horizontal synaptic connections in rat visual cortex in vitro.

The presence of intrinsic horizontal synaptic connections in rat visual cortex was explored electrophysiologically using in vitro slice preparations. Intracellular recordings were made from pyramidal neurons located in the superficial and deep layers. Electrical stimulation at the gray matter in the same or different layers but 0.8-2.7 mm apart from the recording site evoked compound synaptic potentials composed of excitatory and inhibitory postsynaptic potentials of fast and slow time courses. Glutamate blockers, DNQX (5 microM) and kynurenate (2 mM) reduced the excitatory postsynaptic potential (EPSP), and GABAB receptor antagonist, phaclofen (0.5 mM), abolished the inhibitory postsynaptic potential of the slow time course. EPSP of the fast time course followed 20 Hz repetitive stimulation in the medium of high Ca2+ (6.0 mM) and Mg2+ (4.0 mM) concentration, suggesting that this fast EPSP was monosynaptic. Conduction velocity of the fibers mediating the monosynaptic EPSP was estimated to be 0.15-0.55 m/s. These results provide physiological evidence for the horizontal synaptic connections in the rat visual cortex, which had been previously suggested by morphology.

Animals↗

PubMed1997

Transient synaptic potentiation in the visual cortex. II. Developmental regulation.

In our previous study, pairing-induced transient synaptic potentiation in supragranular layers of the visual cortex was described in mature guinea pigs. In the present study, the development of this type of synaptic plasticity and the underlying cellular mechanisms that mediate it were evaluated in animals from postnatal day (PND) 5 to 180. Potentiation is more reliably evoked in younger animals (likelihood: 75%, PND 5-30; 51%, PND > or = 34), and the magnitude of the effect is greater (+40 +/- 3%, mean +/- SE, PND 5-30; +26 +/- 3%, PND > or = 34). Similar to data obtained from the mature animals, visual cortical transient synaptic potentiation in the immature cortex occurs at excitatory synaptic sites directly activated by the stimulation, and activation by local recurrent cortical circuits is not necessary for the induction of this potentiation. This is demonstrated by 1) experiments in which action potential output from the paired neuron was blocked by Lidocaine, N-ethyl bromide quaternary salt applied into the neuron (5 of 5), and 2) experiments in which the contribution to the compound postsynaptic potential by inhibitory synapses was eliminated by selective, intracellular blockade by gamma-aminobutyric acid-mediated inhibitory postsynaptic potentials only onto the recorded neuron (7 of 11). Thus these perturbations do not reduce the likelihood or magnitude of this synaptic potentiation. In contrast to the N-methyl-D-aspartate (NMDA) receptor dependence for induction of this synaptic potentiation in the cortex of mature animals, in the young animals' cortices (PND 11-27) potentiation is readily induced during blockade of NMDA receptors (72%, 13 of 18, did not different from control: 75%, 40 of 53). Thus the NMDA receptor becomes functionally linked to a synaptic potentiation cascade during development, replacing another 2-amino-5-phosphonovaleric acid (APV)-insensitive potentiation process in the neonatal cortex. Postsynaptic intracellular calcium has a critical role in the induction of this form of synaptic potentiation in all ages studied. Synaptic potentiation was prevented (8 of 11 cases) or was replaced by synaptic depression (3 of 11 cells) in experiments in which postsynaptic calcium levels were reduced by intracellular application of 1,2-bis-2-aminophenoxy ethane-N,N,N',N'-tetraacetic acid (BAPTA) in the cortex of young (PND 7-14) animals, or in which the extracellular calcium concentrations was lowered. Inhibition of postsynaptic calcium-induced calcium release blocked synaptic potentiation (4 of 4 cells). Prolonged superfusion (3 h) of the nitric oxide synthase inhibitor L-nitro-arginine (LNA) did not significantly affect the likelihood (in LNA, 81%; 13 of 16 cells), or the magnitude (+38 +/- 7% increase in LNA vs. +40 +/- 3% in control cases) of potentiation, in contrast to its effects in the mature cortex.

Aging↗

PubMed2000

Muscarinic receptors depress GABAergic synaptic transmission in rat midbrain dopamine neurons.

The effects of muscarine and nicotine on evoked and spontaneous release of GABA were studied using intracellular and whole-cell patch-clamp recordings from rat midbrain dopamine neurons in an in vitro slice preparation. Muscarine (30 microM) reversibly depressed the pharmacologically isolated inhibitory postsynaptic potential evoked by local electrical stimulation. The maximal inhibition of the inhibitory postsynaptic potential amplitude was 39.6+/-5%. This depressant effect of muscarine was blocked by the M3/M1 receptor antagonist 4-diphenylacetoxy-N-methylpiperidine methiodide (100 nM), but was slightly affected by the M1/M3 receptor antagonist pirenzepine (1 microM). In addition, muscarine decreased the frequency of the miniature synaptic currents without any effect on their amplitude. Moreover, muscarine did not change the GABA-induced hyperpolarization, indicating that its effect on the inhibitory postsynaptic potential is mediated by presynaptic receptors. On the contrary, the cholinergic agonist nicotine did not change the frequency or the amplitude of the spontaneous glutamatergic and GABAergic synaptic currents. Our data indicate that a prevalent activation of presynaptic M3 muscarinic receptors inhibits the GABA-mediated synaptic events, while the activation of nicotinic receptors does not affect the release of glutamate and GABA on midbrain dopamine neurons.

Animals↗

PubMed1984

Cortically induced postsynaptic potentials in hypoglossal motoneurons after axotomy.

Cortically induced postsynaptic potentials were studied in normal and axotomized cat hypoglossal motoneurons. In normal protruder motoneurons innervating tongue protruder muscles, we have demonstrated that stimulation of the orbital gyrus, at the point optimum for inducing lapping movements of the tongue by repetitive stimuli, produced inhibitory postsynaptic potentials or excitatory postsynaptic potentials followed by predominant inhibitory postsynaptic potentials. The cortically induced excitatory postsynaptic potential in normal protruder motoneurons was composed of only the short-latency component. In protruder motoneurons 30, 40, 60 and 80 days after axotomy, we have demonstrated that the number of protruder motoneurons responding with two components of excitatory postsynaptic potentials (the short- and the long-latency component) to cortical stimulation increased in correspondence with the lapse of days after axotomy and that the amplitude of cortically induced inhibitory postsynaptic potentials in axotomized protruder motoneurons was reduced in size as compared with normal protruder motoneurons.

Animals↗

PubMed1997

Effects of serotonin through serotonin1A and serotonin4 receptors on inhibition in the guinea-pig dentate gyrus in vitro.

The role of serotonin1A and serotonin4 receptors in the modulation of synaptic inhibition in the dentate gyrus of guinea-pig hippocampal slices was studied. The effects of serotonin (5-hydroxytryptamine) on hilar neurons and on inhibitory postsynaptic potentials in granule cells were compared using intracellular recording in the presence of glutamatergic receptor antagonists. On the basis of electrophysiological properties hilar neurons were classified as type I neurons (presumably inhibitory) and type II neurons (presumably excitatory). Serotonin hyperpolarized a proportion of type I hilar neurons (60%) and decreased their input resistance through activation of a K+-conductance. This effect was mediated by serotonin1A receptors since it was mimicked by the selective serotonin1A receptor agonist (+/-)-8-hydroxy-dipropylaminotetralin hydrobromide and blocked by the selective serotonin1A receptor antagonist (+) WAY 100135. In some type I hilar neurons (40%) neither serotonin nor (+/-)-8-hydroxydipropylaminotetralin hydrobromide induced a membrane hyperpolarization. Instead, serotonin induced an excitatory response, depolarizing the cells and blocking the slow afterhyperpolarization. Similar effects were seen in all hilar neurons after blockade of serotonin1A receptors. They were mimicked by the serotonin4 receptor agonist zacopride. Serotonin induced either decreases or increases in the frequency of spontaneous GABA(A) receptor-mediated inhibitory postsynaptic potentials in granule cells via activation of serotonin1A and of serotonin4 receptors, respectively. 4-aminopyridine-evoked GABA(B) receptor-mediated inhibitory postsynaptic potentials were inhibited by serotonin via activation of serotonin1A receptors. However, after blockade of serotonin1A receptors, serotonin increased the frequency of GABA(B)-inhibitory postsynaptic potentials through the activation of serotonin4 receptors. We conclude that a proportion of inhibitory neurons in the dentate area does not express serotonin1A receptors and is excited by serotonin. Other inhibitory neurons express serotonin1A receptors and are inhibited by serotonin.

Animals↗