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PubMed1992

Unitary, quantal and miniature GABA-activated synaptic chloride currents in cultured neurons from the rat superior colliculus.

The aim of this study was to identify the conductance change induced by one quantum of gamma-aminobutyric acid from axonal release sites on cultured superior colliculus neurons. Unitary (single cell-activated) inhibitory postsynaptic currents and spontaneous synaptic activity were recorded with patch clamp techniques in the whole cell configuration while superfusing the entire neuron with normal saline. Miniature inhibitory postsynaptic currents were recorded in the presence of tetrodotoxin and in reduced [Ca2+]o/[Mg2+]o. In addition, the membrane area contributing to synaptic activity was limited to a narrow window of 50 microns. Smaller neurons were chosen for recording to render a standard deviation of the "instrumental" noise of less than 1.5 pA at a holding voltage of -80 mV. After two weeks in vitro, the percentage of synaptically connected tectal neurons exceeded 50%. At holding voltages of -80 mV (Cl- equilibrium potential -12 mV) minimal amplitudes of unitary inhibitory postsynaptic currents were as low as 7-10 pA, while maximal amplitudes exceeded 500 pA. The mean time to peak and time constant of decay were 3.0 and 34.4 ms, respectively (n = 31). Fluctuating unitary inhibitory postsynaptic currents were deemed to be compound postsynaptic responses. Multiple Gaussian equations could be fitted to the amplitude histograms of unitary postsynaptic currents. This procedure rendered a quantal size between 5.0 and 10.9 pA (mean 7.1 pA; S.D. 1.78 pA) in five neurons from mature cultures. The amplitudes of statistically determined quantal inhibitory postsynaptic currents were slightly smaller than the independent estimate from somatic miniature inhibitory postsynaptic currents. The latter had a mean amplitude of 9.1 pA (S.D. 3.3 pA, n = 23), a mean time to peak of 1.65 ms (n = 9), and a mean time constant of decay of 16.2 ms (n = 9). Single channel recording from outside-out patches showed three to four main conductance states ranging from 9 to 22 pS. Single channel closures at the 21-24 pS level were occasionally observed during relaxation of miniature currents. The small size of whole cell quantal inhibitory postsynaptic currents and somatic miniature currents indicates that one GABA quantum opened only 5-15 single Cl- channels.

Animals↗

PubMed1984

Dopaminergic and noradrenergic responses in the hippocampal slice preparation. Evidence for different receptors.

The effects of iontophoretic applications of dopamine (DA) and noradrenaline (NA) on potentials evoked by the stimulation of the hippocampal slice preparations were investigated. Dopamine, ejected at the soma, produced an increase of the amplitude of the population spike of CA1 pyramidal cells; NA had an excitatory action on some responses, inhibitory on others. The field-excitatory postsynaptic potentials (EPSPs) were unaffected by ejection of DA and NA on the dendritic tree. Domperidone, a dopaminergic antagonist, blocked the increase of the population spike induced by DA, but was unable to antagonize noradrenergic responses. Timolol, a beta-adrenergic antagonist, blocked the excitatory action of NA, but did not modify either the effect of DA or the inhibition induced by NA. Phentolamine, an alpha-antagonist, antagonized only the inhibition induced by NA. These results indicate that DA and NA modulate the activity of hippocampal neurones by interacting on different receptors.

Animals↗

PubMed1998

Synchronous firing of inhibitory interneurons results in saturation of fast GABA(A) IPSC magnitude but not saturation of fast inhibitory efficacy in rat neocortical pyramidal cells.

The kinetic properties of evoked fast inhibitory postsynaptic currents were examined to elucidate factors underlying the limit on the magnitude of fast inhibition in neocortex. Using whole-cell voltage-clamp recordings from layer V pyramidal neurons in slices of rat somatosensory cortex, fast gamma-aminobutyric acid-A (GABA[A])ergic inhibitory postsynaptic currents were selectively recorded by holding cells at potentials equal to excitatory postsynaptic current reversal (approximately 0 mV). As stimulus intensity was increased, the magnitude and duration of the fast inhibitory postsynaptic current increased. Over the range of stimuli applied (2-10 V), fast GABA(A)-mediated inhibitory postsynaptic currents reached a maximum peak conductance of 25.9 +/- 4.2 nS (range 10.5-41.2 nS) at intensities approximately 2-times threshold. As stimulus intensities were increased beyond this point of maximal conductance, the time constant of current decay increased as function of stimulus strength, while rise time remained unaffected. Exposure to nominally magnesium-free solutions did not affect maximal peak conductances of fast inhibitory postsynaptic currents, but did cause an increase in the time constants of current decay by 66.3 +/- 23.6%, resulting in an 85.6 +/- 24.6% increase in the total charge flux carried by single inhibitory postsynaptic currents. This effect may be due to prolonged activation of postsynaptic GABA(A) receptors by excess GABA released in response to increased excitation. Exposure to the GABA uptake blocker, nipecotic acid, similarly prolonged current decay without affecting the maximal peak conductance. Our findings suggest that the limit on recruitment of evoked fast inhibition in neocortical layer V pyramidal cells arises from the saturation of postsynaptic GABA(A) receptors. However, while there is a limit to the peak fast inhibitory postsynaptic conductance which can be recruited with increasing excitation, inhibitory strength may still be modulated by increasing charge flux through the prolongation of fast inhibition.

Animals↗

PubMed1993

Membrane properties of organum vasculosum lamina terminalis neurons recorded in vitro.

Intracellular recordings of organum vasculosum lamina terminalis (OVLT) neurons were obtained from superfused explants of rat hypothalamus. Most (32 of 34) OVLT neurons displayed a low threshold spike response during depolarizing pulses applied from holding membrane potentials negative to -70 mV. In 17 of 34 cells, electrical stimulation of the supraoptic nucleus area evoked antidromic responses. In 20 of the 34 cells, 8 of which were antidromically driven, identical stimuli also revealed either excitatory (n = 12) or inhibitory (n = 5) or mixed (n = 3) postsynaptic potentials. Axonal projections to the ipsilateral supraoptic nucleus were confirmed afterwards using reconstruction of Lucifer yellow-filled cells. A 10-40 mosmol/kgH2O increase in the osmolality of the superfusion media by addition of NaCl or mannitol prompted a membrane depolarization of 2-10 mV in each of nine OVLT neurons tested. These results indicate that OVLT neurons project to the supraoptic nucleus and possess intrinsic properties capable of influencing their excitability. Because neurons in OVLT depolarize consequent to elevations in media osmolality, the OVLT may provide a means by which hyperosmotic stimuli influence neuroendocrine function.

Animals↗

PubMed2001

Effect of FK960, a putative cognitive enhancer, on synaptic transmission in CA1 neurons of rat hippocampus.

The action of FK960 [N-(4-acetyl-1-piperazinyl)-p-fluorobenzamide monohydrate], a novel cognitive enhancer, on excitatory synaptic transmission in the hippocampus was investigated. Excitatory postsynaptic potentials (EPSPs) and currents (EPSCs) were recorded intracellularly from CA1 neurons in rat hippocampus using the "blind patch" variant of whole-cell recording. FK960 (100 nM) significantly increased the amplitude of the EPSP, which was unchanged when changeover was made to control artificial cerebrospinal fluid (aCSF). FK960 had no significant action on membrane potential, input resistance, or the early GABAergic inhibitory postsynaptic current. The decay phase of the excitatory postsynaptic current was not significantly altered by exposure to FK960, indicating that the properties of desensitization and/or deactivation were unchanged and suggesting that the action of FK960 was unlikely to be the result of changes in the properties of the postsynaptic (S)-alpha-amino-3-hydroxy-5-methyl-4-isoxazoleproprionic acid (AMPA) receptors. The quantal content of the EPSP (1/CV(2)) increased after exposure to FK960 but not to control aCSF. Methyllycaconitine or alpha-bungarotoxin blocked the modulatory action of FK960 on the EPSP, and the finding that these alpha 7-nicotinic acetylcholine receptor (alpha 7nAChR) antagonists were effective raises the possibility that FK960 up-regulates the contribution of acetylcholine to synaptic efficacy in the hippocampus. It is concluded that FK960 increases the quantal release of glutamate from Schaffer collateral-commissural nerve terminals in area CA1 of the hippocampus either by changing the ambient level of acetylcholine or by positively modulating the activity of alpha 7nAChRs located on glutamatergic nerve terminals.

Aconitine↗

PubMed2004

GABA(B) receptor activation modulates GABA(A) receptor-mediated inhibition in chicken nucleus magnocellularis neurons.

Neurons of nucleus magnocellularis (NM), a division of avian cochlear nucleus that performs precise temporal encoding, receive glutamatergic excitatory input solely from the eighth nerve and GABAergic inhibitory input primarily from the ipsilateral superior olivary nucleus. GABA activates both ligand-gated Cl- channels [GABA(A) receptors (GABA(A)Rs)] and G protein-coupled receptors (GABA(B) receptors). The net effect of GABA(A)R-mediated input to NM is inhibitory, although depolarizing. Several studies have shown that this shunting, inhibitory GABAergic input can evoke action potentials in postsynaptic NM neurons, which could interfere with their temporal encoding. While this GABA-mediated firing is limited by a low-voltage-activated K+ conductance, we have found evidence for a second mechanism. We investigated modulation of GABA(A)R-mediated responses by GABA(B)Rs using whole cell recording techniques. Bath-applied baclofen, a GABA(B)R agonist, produced dose-dependent suppression of evoked inhibitory postsynaptic currents (eIPSCs). This suppression was blocked by CGP52432, a potent and selective GABA(B)R antagonist. Baclofen reduced the frequency but not the amplitude of miniature IPSCs (mIPSCs) and did not affect postsynaptic currents elicited by puff application of a specific GABA(A)R agonist muscimol, suggesting a presynaptic mechanism for the GABA(B)R-mediated modulation. Firing of NM neurons by synaptic stimulation of GABAergic inputs to NM was eliminated by baclofen. However, endogenous GABA(B)R activity in the presynaptic inhibitory terminals was not observed. We propose that presynaptic GABA(B)Rs function as autoreceptors, regulating synaptic strength of GABA(A)R-mediated inhibition, and prevent NM neurons from generating firing during activation of the inhibitory inputs.

Analysis of Variance↗

PubMed1995

Selective block of Ca(2+)-dependent K+ current in crayfish neuromuscular system and chromaffin cells by sea anemone Bunodosoma cangicum venom.

The effects of the nematocyst venom of the sea anemone Bunodosoma cangicum on depolarization-activated currents were studies in opener crayfish muscle fibers and in cultured bovine chromaffin cells. The venom selectively and reversibly blocked the Ca(2+)-dependent K+ current (IK(Ca)) present in crayfish muscle in a dose-dependent manner without affecting voltage-gated Ca2+ or K+ currents. Furthermore, the venom also reduced IK(Ca) in chromaffin cells, without modifying voltage-gated Na+, Ca2+, or K+ currents. Synaptic transmission in crayfish muscle was also affected by the venom. Repetitive excitatory and inhibitory postsynaptic currents (each associated with a presynaptic action potential) were evoked by each nerve stimulus, suggesting that presynaptic IK(Ca) may control the electrical activity of excitatory and inhibitory presynaptic fibers. We conclude that B. cangicum venom includes a toxin that selectively and reversibly blocks Ca(2+)-dependent K+ currents in crayfish muscle and in bovine chromaffin cells, and modifies excitatory and inhibitory synaptic transmission, probably abolishing a similar conductance at the presynaptic fibers.

Animals↗

PubMed2005

Benzodiazepine involvement in LTP of the GABA-ergic IPSC in rat hippocampal CA1 neurons.

Benzodiazepine binding sites are present on gamma-aminobutyric acid (GABA) receptors in hippocampal neurons. Diazepam is known to potentiate the amplitude and prolong the decay of GABA(A) receptor-mediated inhibitory postsynaptic currents (IPSCs). In this study, benzodiazepine involvement in long-term potentiation (LTP) of the IPSC was examined. Whole-cell recordings of IPSCs were made from rat hippocampal CA1 neurons in a slice preparation. LTP was induced by a tetanic stimulation in the stratum radiatum (2 trains of 100 Hz for 1 s, 20 s inter-train interval) while pharmacologically blocking ionotropic glutamate receptors. During LTP, the amplitude of the IPSCs was potentiated in the majority of neurons with the IPSC decay and shape unaffected. Diazepam (5 microM) potentiated the IPSC amplitude and prolonged the decay when applied before, but not during, LTP. In neurons in which LTP could not be induced by a tetanic stimulation, diazepam did not increase the amplitude of the pre-tetanic IPSC. Flumazenil, at a concentration (10 microM) that blocked the enhancement of the IPSC by applied diazepam, had no effect on the IPSC amplitude when applied before LTP induction but significantly decreased the IPSC when applied during LTP maintenance. The antagonist, when applied during the tetanic stimulation, did not block LTP, suggesting that benzodiazepine receptors do not participate in LTP induction. These results indicate that the maintenance of LTP of the IPSC involves (a) the release of endogenous benzodiazepine agonist(s) and/or (b) the participation of benzodiazepine binding sites on subsynaptic GABA(A) receptors.

Action Potentials↗

PubMed1997

Activity-dependent potentiation of synaptic transmission from L30 inhibitory interneurons of aplysia depends on residual presynaptic Ca2+ but not on postsynaptic Ca2+.

Activity-induced short-term synaptic enhancement (STE) is a common property of neurons, one that can endow neural circuits with the capacity for rapid and flexible information processing. Evidence from a variety of systems indicates that the expression of STE depends largely on the action of residual Ca2+, which enters the presynaptic terminal during activity. We have shown previously that a Ca2+-dependent STE in the inhibitory synapse between interneurons L30 and L29 in the abdominal ganglion of Aplysia californica has a functional role in regulating the gain of the siphon withdrawal circuit through facilitated recurrent inhibition onto the L29s. In the present paper, we further explore the role of Ca2+ in L30 STE by examining two basic issues: 1) What is the role of residual presynaptic Ca2+ in the maintenance of L30 STE? We examine this question by first inducing STE in the L30s then rapidly buffering presynaptic free calcium through the use of the photoactivated Ca2+ chelator diazo-4, which was preloaded into the L30 neurons. Three forms of STE in the L30s were examined: frequency facilitation (FF), augmentation (AUG), and posttetanic potentiation (PTP). In each case, the activation-induced enhancement of the L30 to L29 synapse was reduced to preactivation levels at the first test pulse following photolysis of diazo-4. 2) What is the role of postsynaptic Ca2+ in the induction of L30 STE? We examine whether there is a postsynaptic requirement of elevated Ca2+ for the induction of L30 STE by first injecting the calcium chelator bis-(o-aminophenoxy)-N,N,N',N'-tetraacetic acid (BAPTA) into the postsynaptic cell L29 (at levels sufficient to block transmitter release from the L29s), to prevent any increase in postsynaptic intracellular Ca2+ that may occur during L30 (presynaptic) activation. We found that BAPTA injection did not effect either the induction or the time course of FF, AUG, or PTP in the L30s. Taken collectively, our data indicate that all forms of STE in the L30s depend on presynaptic free cytosolic Ca2+ for their maintenance but do not require the elevation of postsynaptic Ca2+ for their induction.

Animals↗

PubMed1981

Analysis of miniature spontaneous inhibitory postsynaptic currents (sIPSCs) from current noise in crayfish opener muscle.

Deviating from the normal situation, some crayfish muscle fibres showed spontaneous inhibitory activity: discharge of large inhibitory postsynaptic currents, IPSCs, alternating with long lasting bursts of current noise. Analysis of the bursts of current noise revealed that they are composed of spontaneous miniature unit currents, sIPSCs. In the burst periods the sIPSCs occurred with an average rate of 3.5--10 k Hz and had an amplitude of about alpha = 90 pA at a driving force delta E = 10 mV. The peak conductance gamma alpha = alpha/delta E of the sIPSCs was gamma alpha = 9.2 nS +/- 0.5 (S.D., n = 5) for membrane potentials between E = --60 mV and E = --80 mV. gamma alpha seemed to decrease when the membrane was hyperpolarized. The time constants of decay, tau of the sIPSCs were identical with tau of the IPSCs. Further, tau and its potential dependence agreed with the mean lifetimes of inhibitory postsynaptic channels operated by gamma-aminobutyric acid (GABA) [Dudel et al. 1977, 1980]. Synchronized opening of about 750 inhibitory synaptic channels generates a sIPSC. Analysis of this anomalous bursting inhibitory activity thus yields the size of the inhibitory quantum of transmission, which could not be obtained from IPSCs.

Animals↗

PubMed2006

Benzodiazepine inhibits hypothalamic presympathetic neurons by potentiation of GABAergic synaptic input.

Presympathetic neurons in the paraventricular nucleus (PVN) of the hypothalamus receive inputs from gamma-aminobutyric acid (GABA)-containing neurons, which regulate sympathetic outflow and cardiovascular function. Benzodiazepines can decrease blood pressure and sympathetic nerve activity when used for induction of anesthesia, but the sites and mechanisms of action are uncertain. In this study, we determined the effect of the benzodiazepine agonist diazepam on GABAergic inhibitory postsynaptic currents (IPSCs) and the firing activity of rostral ventrolateral medulla (RVLM)-projecting PVN neurons. RVLM-projecting PVN neurons were retrogradely labeled by fluorescent microspheres injected into the RVLM in rats. Whole-cell and cell-attached recordings were performed on labeled PVN neurons in the hypothalamic brain slice. Bath application of 1-10 microM diazepam significantly increased the decay time constants of the GABAergic miniature IPSCs and evoked IPSCs in a dose-dependent manner. Also, diazepam significantly increased the amplitude of evoked IPSCs but not of miniature IPSCs. Pretreatment with the benzodiazepine antagonist flumazenil completely blocked the diazepam-induced increases in the amplitude and decay time constants of the evoked IPSCs. Furthermore, diazepam significantly decreased the firing activity of PVN-RVLM neurons that responded with increased firing to the GABA(A) receptor antagonist bicuculline. In contrast, diazepam had no significant effect on the firing activity of bicuculline-unresponsive PVN-RVLM neurons. This study provides new information that the benzodiazepine suppresses the firing activity of PVN presympathetic neurons by potentiation of GABAergic inputs.

Action Potentials↗

PubMed2000

Neuropeptide Y reduces epileptiform discharges and excitatory synaptic transmission in rat frontal cortex in vitro.

Neuropeptide Y reduced spontaneous and stimulation-evoked epileptiform discharges in rat frontal cortex slices perfused with a magnesium-free solution and with the GABA(A) receptor antagonist picrotoxin. To investigate the mechanism of that action, effects of neuropeptide Y on intrinsic membrane properties and synaptic responses of layer II/III cortical neurons were studied using intracellular recording. Neuropeptide Y (1 microM) had no detectable effect on the membrane properties of neurons. The evoked synaptic potentials were attenuated by neuropeptide Y. Moreover, the pharmacologically isolated excitatory postsynaptic potentials, mediated by N-methyl-D-aspartate and non-N-methyl-D-aspartate receptors, were reversibly depressed by neuropeptide Y. The most pronounced inhibitory effect of neuropeptide Y was observed on late polysynaptic excitatory postsynaptic potentials. To assess a putative postsynaptic action of neuropeptide Y, N-methyl-D-aspartate was locally applied in the presence of tetrodotoxin. The N-methyl-D-aspartate-evoked depolarizations were unaffected by neuropeptide Y, which suggests that the depression of excitatory postsynaptic potentials was due to an action at sites presynaptic to the recorded neurons. These data show that neuropeptide Y attenuates epileptiform discharges and the glutamate receptor-mediated synaptic transmission in the rat frontal cortex. The above results indicate that neuropeptide Y may regulate neuronal excitability within the cortex, and that neuropeptide Y receptors are potential targets for an anticonvulsant therapy.

Animals↗

PubMed1991

[The convergence of influences from the locomotor points of the midbrain and medulla oblongata and from the inhibitory point of the pons onto the bulbar neurons].

Synaptic responses of medial and lateral medullary neurons to repetitive stimulation of locomotor points (LPs) of the midbrain and medulla and of an inhibitory pontine point were recorded in mesencephalic decerebellate cats. Excitatory postsynaptic potentials (PSPs) and discharges were observed usually in medial neurons as well as mixed PSPs when an inhibitory point was stimulated. Almost a half of lateral neurons and more than a quarter of medial ones changed the frequency of the background discharge giving no responses time-locked to stimuli. Medial neurons with responses time-locked to stimuli were equally susceptible to stimuli delivered to midbrain and medullary LPs and almost as often to stimuli applied to the inhibitory point. Medial neurons with responses time-unlocked to stimuli and lateral neurons were mostly susceptible to the input from the medullary LP, less affected by stimulation of the midbrain LP and responded rarely to stimulation of the inhibitory point. Convergence of influences from the midbrain and medullary LPs was the same onto neurons of all populations. Role of different neuronal populations for initiation and cessation of locomotion is discussed.

Animals↗

PubMed2002

cGMP-induced presynaptic depression and postsynaptic facilitation at glutamatergic synapses in visual cortex.

The mechanisms by which the intracellular messenger cGMP can modulate synaptic efficacy remain poorly understood. Here we report that cGMP, acting through cGMP-dependent protein kinase (PKG), has multiple rapid and reversible effects on synaptic transmission in slices and cultures of rodent visual cortex. Extracellular application of the membrane permeable cGMP analog 8-bromoguanosine-3',5'-cyclic monophosphate (8-Br-cGMP) and the PKG specific activator beta-phenyl-1,N2-etheno-8-bromoguanosine-3',5'-cyclic monophosphorothioate sp-isomer (Sp-8-Br-PET-cGMPS) reduced stimulus-evoked EPSPs in slices. In cortical cultures, both analogs reduced the frequency of spontaneous EPSCs, but not their amplitude. In both slices and cultures, intracellular perfusion of the postsynaptic neurons with a pseudosubstrate inhibitory peptide specific for PKG had no effect on the reduction in EPSPs and EPSCs, indicating that the inhibition occurred at presynaptic sites. Whole-cell calcium currents in cultured cortical neurons were also reduced by both analogs, which may account for the effect on synaptic release. To determine whether cGMP was also acting at postsynaptic sites, we applied exogenous kainate/AMPA and NMDA to the recorded cells directly. cGMP and its analogs showed little effect on the postsynaptic kainate/AMPA responses but produced a dramatic enhancement of NMDA responses. cGMP-induced NMDA potentiation was prevented by the specific PKG inhibitory peptide infused into the postsynaptic cell. In summary, cGMP, acting through PKG, had depressive presynaptic and facilitatory postsynaptic actions at excitatory synapses in the visual cortex. We suggest that these opposing actions may be useful for altering the balance of synaptic inputs to cortical neurons in ways that enhance signals important for synaptic facilitation and neuronal plasticity.

Animals↗

PubMed2005

Synaptic input of rat spinal lamina I projection and unidentified neurones in vitro.

Spinal lamina I projection neurones that transmit nociceptive information to the brain play a pivotal role in hyperalgesia in various animal models of inflammatory and neuropathic pain. Consistently, activity-dependent long-term potentiation can be induced at synapses between primary afferent C-fibres and lamina I projection neurones but not unidentified neurones in lamina I. The specific properties that enable projection neurones to undergo long-term potentiation and mediate hyperalgesia are not fully understood. Here, we have tested whether lamina I projection neurones differ from unidentified neurones in types or strength of primary afferent input and/or action potential-independent excitatory and inhibitory input. We used the whole-cell patch-clamp technique to record synaptic currents in projection and unidentified lamina I neurones in a transverse lumbar spinal cord slice preparation from rats between postnatal day 18 and 37. Lamina I neurones with a projection to the parabrachial area or the periaqueductal grey were identified by retrograde labelling with a fluorescent tracer. The relative contribution of NMDA receptors versus AMPA/kainate receptors to C-fibre-evoked excitatory postsynaptic currents of lamina I neurones significantly decreased with age between postnatal day 18 and 27, but was independent of the supraspinal projection of the neurones. We did not find a significant contribution of kainate receptors to C-fibre-evoked excitatory postsynaptic currents. Lamina I projection and unidentified neurones possessed functional GABAA and glycine receptors but received scarce action potential-independent spontaneous GABAergic and glycinergic inhibitory input as measured by miniature inhibitory postsynaptic currents. The miniature excitatory postsynaptic current frequencies were five times higher in projection than in unidentified neurones. The predominance of excitatory synaptic input to projection neurones, taken together with the previous finding that their membranes are more easily excitable than those of unidentified neurones, may facilitate the induction of synaptic long-term potentiation.

Action Potentials↗

PubMedDate not supplied

Modeling of substance P and 5-HT induced synaptic plasticity in the lamprey spinal CPG: consequences for network pattern generation.

Consequences of synaptic plasticity in the lamprey spinal CPG are analyzed by means of simulations. This is motivated by the effects substance P (a tachykinin) and serotonin (5-hydroxytryptamin; 5-HT) have on synaptic transmission in the locomotor network. Activity-dependent synaptic depression and potentiation have recently been shown experimentally using paired intracellular recordings. Although normally activity-dependent plasticity presumably does not contribute to the patterning of network activity, this changes in the presence of the neuromodulators substance P and 5-HT, which evoke significant plasticity. Substance P can induce a faster and larger depression of inhibitory connections but potentiation of excitatory inputs, whereas 5-HT induces facilitation of both inhibitory and excitatory inputs. Changes in the amplitude of the first postsynaptic potential are also seen. These changes could thus be a potential mechanism underlying the modulatory role these substances have on the rhythmic network activity. The aim of the present study has been to implement the activity dependent synaptic depression and facilitation induced by substance P and 5-HT into two alternative models of the lamprey spinal locomotor network, one relying on reciprocal inhibition for bursting and one in which each hemicord is capable of oscillations. The consequences of the plasticity of inhibitory and excitatory connections are then explored on the network level. In the intact spinal cord, tachykinins and 5-HT, which can be endogenously released, increase and decrease the frequency of the alternating left-right burst pattern, respectively. The frequency decreasing effect of 5-HT has previously been explained based on its conductance decreasing effect on K(Ca) underlying the postspike afterhyperpolarization (AHP). The present simulations show that short-term synaptic plasticity may have strong effects on frequency regulation in the lamprey spinal CPG. In the network model relying on reciprocal inhibition, the observed effects substance P and 5-HT have on network behavior (i.e., a frequency increase and decrease respectively) can to a substantial part be explained by their effects on the total extent and time dynamics of synaptic depression and facilitation. The cellular effects of these substances will in the 5-HT case further contribute to its network effect.

Action Potentials↗

PubMed1981

Mode of the excitatory and inhibitory actions of ciguatoxin in the guinea-pig vas deferens.

Ciguatoxin (CTX), one of the most potent known toxic substances among marine toxins, causes a contraction in the isolated guinea-pig vas deferens at the concentration of above 3 x 10(-7) g/ml. The CTX-induced contraction of the vas deferens was inhibited or abolished by a treatment with phentolamine or guanethidine, but not affected in the presence of atropine or mecamylamine. Furthermore, this contraction was blocked by a treatment with tetrodotoxin, procaine or cold storage and incubation in a low Na+ medium. On the other hand, CTX markedly potentiated the contraction of vas deferens which was induced by norepinephrine (NE), acetylcholine or high-K, whereas it inhibited the contractile response to transmural stimulation. CTX caused a marked release of NE from the adrenergic nerves, which was blocked after treatment with tetrodotoxin or incubation in a Ca-free medium. On the basis of these results, it is suggested that the CTX-induced contraction is the result of an indirect action mediated through the NE release from the adrenergic nerve terminals and that the effect of NE released from the presynaptic sites is potentiated by CTX at the postsynaptic sites. The inhibitory effect of CTX on the contractile response to transmural stimulation may be due to decreasing the transmitter release caused by stimulation.

Animals↗

PubMed2003

Ethanol modulation of excitatory and inhibitory synaptic transmission in rat and monkey dentate granule neurons.

BACKGROUND: The physiological mechanisms underlying the behavioral and cognitive effects of ethanol are not fully understood. However, there is now compelling evidence that ethanol acts, at least in part, by modulating the function of a small group of proteins that mediate excitatory and inhibitory synaptic transmission. For example, intoxicating concentrations of ethanol have been shown to enhance GABAergic synaptic inhibition and depress glutamatergic excitatory neurotransmission in a number of brain regions. Because all of these electrophysiological studies have been performed in rodent brain slice or neuronal culture preparations, direct evidence that ethanol exerts similar effects on synaptic transmission in the primate central nervous system is lacking. METHODS: We have therefore developed methods to perform patch-clamp electrophysiological recordings from neurons in acutely prepared monkey (Macaca fascicularis) hippocampal slices. We have used these methods to compare the acute effects of ethanol on excitatory and inhibitory synaptic transmission in rat and monkey dentate granule neurons. RESULTS: Under our recording conditions, ethanol significantly potentiated gamma-aminobutyric acid type A inhibitory postsynaptic currents in both rat and monkey neurons. In addition, ethanol significantly inhibited NMDA, but not AMPA, excitatory postsynaptic currents in dentate granule neurons from both species. Notably, no significant differences were observed in any of the pharmacological properties of inhibitory or excitatory synaptic responses recorded from rat and monkey neurons. CONCLUSIONS: These data suggest that the differences in the behavioral effects of ethanol that have been observed between rats and higher-order mammals, such as monkeys and humans, may not reflect differences in the sensitivity of some of the major synaptic sites of ethanol action. Moreover, our results provide empirical evidence for the use of rodent brain slice preparations in elucidating synaptic mechanisms of ethanol action in the primate central nervous system.

Animals↗