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PubMed2006

Effects of sub-chronic lithium treatment on synaptic plasticity in the dentate gyrus of rat hippocampal slices.

Although it has long been suggested that lithium has robust neuroplastic actions, and these actions lead to an enhancement on synaptic plasticity, the effects of lithium treatment on synaptic plasticity have been rarely studied. This study examined the effects of sub-chronic lithium treatment on synaptic plasticity in the dentate gyrus (DG) of hippocampal slices in the rats. Young adult rats were intraperitoneally administered a daily dose of 1 mgEq LiCl or saline-vehicle for 14 days. Twelve hours after the last injections, the input/output (I/0) responses of field excitatory postsynaptic potentials (fEPSP) and the long-term potentiation (LTP) of fEPSP and population spikes (PS) were determined in the DG of hippocampal slices prepared from the animals treated with lithium or vehicle. Treatment of lithium for 14 days significantly increased the I/O responses of fEPSP and the LTP of fEPSP and PS. These results indicate that sub-chronic treatment of lithium increases the excitatory postsynaptic responses, synaptic strength and the cell firing of the granule cells in the DG of the hippocampus.

Animals↗
PubMed2005

Enhancement of the synchronized firing of CA1 pyramidal cells by medial septum preconditioning: time-dependent involvement of muscarinic cholinoceptors and GABAB receptors.

Activation of the medial septum (MS) enhances the synchronized firing of pyramidal cells in the hippocampus. At least two distinct mechanisms might be recruited in this process: GABAergic inhibition of hippocampal inhibitory interneurons and cholinergic enhancement of pyramidal cell excitability. In the present study, a field potential recording in urethane anaesthetised rats was used to show that MS preconditioning with brief high-frequency burst stimulation markedly enhanced Schaffer collateral/commissural (SC/C) synaptically evoked population spikes in the CA1 area without significant alteration in the initial slope of SC/C field excitatory postsynaptic potentials (fEPSPs). An early phase (< approximately 125 ms) of the facilitation of neuronal discharge was inhibited by intracerebroventricular (i.c.v.) injection of the GABA(B) receptor antagonist CGP 52432 (200 nmol/5 microl). In contrast, the muscarinic cholinoceptor antagonist scopolamine (20 nmol/5 microl) inhibited a later phase ( approximately 150-300 ms) of the population spike facilitation. These findings support an important role for both cholinergic and GABAergic mediated septal drive in the tuning of signal conversion within the hippocampus as well as in securing the cortical feedback from the hippocampus.

Animals↗
PubMed2002

Ethanol withdrawal results in aberrant membrane properties and synaptic responses in periaqueductal gray neurons associated with seizure susceptibility.

The midbrain periaqueductal gray (PAG) is implicated as a component of the neuronal network for ethanol withdrawal (ETX) seizures and in other forms of audiogenic seizure (AGS) in rats. Previous in vivo experiments suggest that neurons in the ventrolateral PAG (VL PAG) are required for generation of the clonic and tonic seizure behaviors of AGS. During these seizures, PAG neuronal firing rates increase markedly, but the intracellular events, contributing to this phenomenon, have not been characterized. In the present in vitro study, intracellular current-clamp recordings were obtained from 115 control VL PAG neurons and 71 neurons during ETX. The amount of depolarizing current that needed to be injected into ETX neurons in order to generate an action potential (AP) (N=40) was significantly less than control (N=52). ETX also yielded a significant leftward shift in the frequency-current curve of VL PAG neurons. VL PAG neurons during ETX had significantly enhanced spike firing tendencies, but the firing pattern was similar in ETX and control. ETX significantly increased the incidence of spontaneous APs and the frequency of firing above those in control. A number of cellular properties [e.g. resting membrane potential (RMP), amplitude of AP, AP width at half-height, input resistance and time constant] did not differ significantly between ETX and control neurons. The current-voltage (I-V) relationships of the ETX and control VL PAG neurons were nearly linear between RMP and 80 mV more negative than RMP, whereas the I-V relation was non-linear beyond this range. Stimulation in the dorsolateral PAG in either ETX or control neurons evoked a fast excitatory postsynaptic potential (EPSP) and a slow inhibitory postsynaptic potential (IPSP). The stimulus intensities required to evoke EPSPs were significantly lower than control in neurons during ETX. Epileptiform firing was observed commonly (20%) during ETX but was never seen in control rats. Paired-pulse responses evoked paired-pulse inhibition in approximately 80% of VL PAG neurons from control rats (N=38), which was significantly above the incidence (12%) of this pattern during ETX (N=25). Paired-pulse facilitation was significantly more common (88%) in VL PAG neurons (N=25) during ETX compared to approximately 20% in controls (N=38). These aberrant membrane and synaptic properties provide direct evidence regarding the basis of the hyperexcitability observed in VL PAG neurons in vivo that contribute to propagation mechanisms of clonic and tonic convulsions, occurring during ETX.

Action Potentials↗
PubMed1998

Development of a transient increase in recurrent inhibition and paired-pulse facilitation in hippocampal CA1 region.

Paired-pulse recurrent inhibition (RI) of population spike (PS) and facilitation (PPF) of field excitatory postsynaptic potential (EPSP) were studied in the CA1 region of hippocampal slices taken from Wistar rats aged from 9 days to 16 months. The comparison of three different paired-pulse protocols revealed the antidromic-orthodromic (A-O) stimulation as the most reliable in quantifying the strength of fast (peaking at 10 ms) and slow (peaking at 200 ms) components of recurrent inhibition. Fast RI, present but weak at 9 days, progressively increased to reach its maximal strength at 30 days, declining in adult (2 m) and middle-aged (16 m) animals. Slow RI was replaced by facilitation at 9 days while it was absent at 15 days. It reached adult values at 30 days. A reduction of the test response at interpulse interval (IPI) of 2-4 ms was strong in developing and adult animals, but was significantly decreased in 16 m. At maximal stimulation PPF was expressed as an enhancement of the slow rather than the fast phase of the EPSP and was particularly strong with a prominent N-methyl-D-aspartate dependent component. A very characteristic selectivity for a prominent PPF at stimulation frequency of 5 Hz appeared first at the 18th day and increased gradually to reach a maximum at the 30th day, after which it declined to very low values in middle-aged animals. A similar developmental pattern was observed in slices taken from rats reared in complete darkness, suggesting a strong innate origin. The ability of hippocampal circuits for plastic gating of information appears to be transiently enhanced at the completion of the first postnatal month as it can be exercised at a wider part of the frequency spectrum, with maximal inhibition and potentiation especially at the frequency of theta rhythm.

Age Factors↗
PubMed2000

Spatial learning and long-term potentiation in the dentate gyrus of the hippocampus in animals developmentally exposed to Aroclor 1254.

Developmental exposure to polychlorinated biphenyls (PCBs) has been associated with cognitive deficits in children. Rodent studies have revealed impairments in learning tasks involving the hippocampus. The present study sought to examine hippocampal synaptic plasticity in the dentate gyrus and spatial learning in animals exposed to PCBs early in development. Pregnant Long-Evans rats were administered either corn oil (control) or 6 mg/kg/day of a commercial PCB mixture, Aroclor 1254 (A1254) by gavage from gestational day (GD) 6 until pups were weaned on postnatal day (PND) 21. Spatial learning was assessed at 3 months of age in male and female offspring using the Morris water maze. Latency to find a hidden platform that remained in the same position over 20 days of testing did not differ between control and PCB-exposed groups. Neither were group differences evident in a repeated acquisition version of the task in which the platform remained in the same position over the 2 daily trials but was moved to a new spatial location each day. Male littermates of animals in the behavioral study were tested electrophysiologically at 5-7 months of age. Field potentials evoked by perforant path stimulation were recorded in the dentate gyrus under urethane anesthesia. Input/output (I/O) functions were assessed by averaging the response evoked in the dentate gyrus to stimulus pulses delivered to the perforant path in an ascending intensity series. Long-term potentiation (LTP) was induced by delivering a series of brief, high-frequency train bursts to the perforant path at increasing stimulus intensities, and I/O functions were reassessed 1 h later. No differences in baseline synaptic population spike (PS) and excitatory postsynaptic potential (EPSP) slope amplitudes were discerned between the groups prior to train delivery. Post-train I/O functions, however, revealed a decrement in the magnitude of evoked LTP in PCB-exposed animals, and an increase in the train intensity required to induce LTP. The observed dissociation between impaired hippocampal plasticity, in the absence of a detectable deficit in performance of a hippocampal-dependent task, may be due to task complexity, the maintenance of some degree of plasticity in the PCB-exposed animals, or the possibility that intact dentate gyrus LTP may not be requisite for water-maze learning.

Animals↗
PubMed2000

Dynorphin exerts both postsynaptic and presynaptic effects in the Globus pallidus of the rat.

The opioids contained in striato-pallidal axons are thought to play a significant role in motor control. We examined post- and presynaptic effects of the kappa (kappa)-receptor agonist dynorphin A (1-13) (DYN13) on the globus pallidus (GP) neurons in rat brain slice preparations using the whole cell recording method. DYN13 hyperpolarized and decreased the input resistance of approximately one-quarter of neurons examined. All of these DYN13-sensitive neurons had medium-sized somata, large aspiny dendrites and generated repetitive firing without strong accommodation. The hyperpolarization was blocked by barium and was independent of TTX and intracellular chloride levels. The hyperpolarization was also selectively blocked by the kappa-antagonist nor-binaltorphimine dihydrochloride but not by the mu- or delta-antagonists. These data suggested that DYN13 activates barium-sensitive potassium currents in some GP neurons. Low- and high-intensity stimulation of the neostriatum (Str) evoked long- and short-latency GABAergic responses, respectively. Previous data suggested that the long- and the short-latency responses were due to activation of the striato-pallidal axons and the local collaterals of pallido-striatal axons, respectively. DYN13 diminished the amplitude of both the short- and long-latency GABAergic responses in all the neurons tested. The effects of DYN13 on GABAergic postsynaptic responses were also selectively blocked by a kappa-antagonist. To investigate whether the effects were pre- or postsynaptic, the effects of DYN13 on spontaneous inhibitory postsynaptic potentials (IPSPs) and TTX-independent miniature-inhibitory postsynaptic currents (IPSCs) were examined. DYN13 decreased the frequency, but not the amplitude, of spontaneous IPSCs and calcium-dependent miniature-IPSCs. However, DYN13 did not alter the cadmium-insensitive miniature-IPSCs. These results suggested that DYN13 suppressed GABA release from presynaptic terminals. This possibility was tested using a paired-stimulation test. DYN13 reduced the probability of evoking IPSCs to the first stimulation and greatly increased the success probability to the second stimulus. The amplitude of successfully evoked IPSCs was not changed with DYN13. DYN13 did not affect the excitatory postsynaptic potentials (EPSPs) or the response to iontophoretically applied GABA and glutamate. Together, these results suggest that DYN released from striato-pallidal axons controls the activity of GP neurons 1) by directly hyperpolarizing a population of neurons and 2) by presynaptically inhibiting GABA release from striato-pallidal and intrapallidal terminals.

Animals↗
PubMed1999

Effects of interleukin-1 beta on neurons in mammalian pelvic ganglia.

The effects of interleukin-1 beta (IL-1 beta) on the membrane potential and synaptic transmission were examined in neurons of mammalian pelvic ganglia. Bath-application of recombinant human IL-1 beta (6-300 pM) for 10 s-5 min produced a long-lasting hyperpolarization associated with increased input resistance in 11 neurons of rat major pelvic ganglia (MPG). In other 8 neurons, IL-1 beta (300 pM) produced a biphasic response that consists of an initial depolarization followed by a long-lasting hyperpolarization. IL-1 beta 163-171 (10-100 pM), a synthetic nonapeptide analog that contains the active domain of human IL-1 beta, mimicked the effect of IL-1 beta in MPG neurons. gamma-Aminobutyric acid (GABA, 300 microM) produced a depolarization followed by a hyperpolarization that was blocked by picrotoxin (100 microM). Db-cyclic guanosine monophosphate (db-cyclic GMP, 100 microM) also produced an initial depolarization followed by a long-lasting hyperpolarization. These results suggest that the IL-1 beta-induced biphasic response is mediated by a GABA receptor-cyclic GMP pathway. IL-1 beta and IL-1 beta 163-171 caused an initial facilitation followed by a long-lasting depression of the excitatory postsynaptic potential (EPSP) in rabbit VPG. The data suggest that IL-1 beta presynaptically depressed the EPSP by reducing the release of acetylcholine (ACh) from the pelvic nerve terminals.

Animals↗
PubMed1999

Endomorphin-like immunoreactivity in the rat dorsal horn and inhibition of substantia gelatinosa neurons in vitro.

Endomorphin 1 and 2 are two tetrapeptides recently isolated from bovine as well as human brains and proposed to be the endogenous ligand for the mu-opiate receptor. Opioid compounds expressing mu-receptor preference are generally potent analgesics. The spinal cord dorsal horn is considered to be an important site for the processing of sensory information including pain. The discovery that endomorphins produced greater analgesia in mice upon intrathecal as compared to intracerebroventricular injections raises the possibility that dorsal horn neurons may represent the anatomic site upon which endomorphins exert their analgesic effects. We report here the detection of endomorphin 2-immunuoreactive fiber-like elements in superficial layers of the rat dorsal horn by immunohistochemical techniques. Whole-cell patch recordings from substantia gelatinosa neurons of cervical spinal cord slices revealed two conspicuous effects of exogenously applied endomorphin 1 and 2: (i) depression of excitatory postsynaptic potentials evoked by stimulation of dorsal root entry zone, and (ii) hyperpolarization of substantia gelatinosa neurons. These effects were reversed by the selective mu-opiate receptor antagonist beta-funaltrexamine. Collectively, the detection of endomorphin-like immunoreactivity in nerve fibers of the superficial layers and the inhibitory action of endomorphins on substantia gelatinosa neurons provide further support for a potential role of these two peptides in spinal nociception.

Animals↗
PubMedDate not supplied

Imipramine-induced increase in the inhibitory effect of adenosine receptor activation in the hippocampus.

Imipramine, a tricyclic antidepressant, is one of the main drugs used for the treatment of depression. We investigated the effects of the repeated administration of imipramine (10 mg/kg po for 14 days, twice daily) on adenosine receptor-mediated actions using extracellular and intracellular recording techniques in the rat hippocampal slices. Adenosine and 2-chloroadenosine dose-dependently decreased the amplitude of population spikes and the slope of the field excitatory postsynaptic potentials (fEPSPs) evoked in the CA1 cell layer and apical dendrites of the CA1 cells, respectively, by stimulation of the Schaffer collateral/commissural pathway. As revealed by intracellular recording, a membrane hyperpolarization and a strong attenuation of excitatory synaptic transmission contribute to the decrease in the population spikes and fEPSPs induced by adenosine and 2-chloroadenosine. The repeated administration of imipramine enhanced the effect of adenosine (3 microM) and 2-chloroadenosine (0.15 microM) on fEPSPs while the inhibition of population spikes was not changed. When higher concentration of 2-chloroadenosine (0.25 microM) was tested, repeated imipramine administration enhanced its inhibitory effect on population spikes but not on fEPSPs. The present report provides evidence that the inhibitory effect of adenosine receptor activation in the hippocampus is enhanced by repeated treatment with imipramine.

2-Chloroadenosine↗
PubMed1999

Mechanism underlying increased neuronal activity in the rat ventrolateral periaqueductal grey by a mu-opioid.

1. The overall effect of the mu-opioid receptor agonist DAMGO (Tyr-D-Ala-Gly-MePhe-Gly-ol) on ventrolateral periaqueductal grey (PAG) neurons in brain slices was studied using the whole-cell patch-clamp recording technique. 2. Under current-clamp conditions, DAMGO (1 microM) increased cell firing in many PAG neurons even though the opioid induced hyperpolarization and inhibited excitatory postsynaptic potentials (EPSPs) in these cells. 3. The increase in cell activity by DAMGO was observed in both transverse and horizontal slices. The increase persisted when the membrane potential was re-depolarized to the control level. Thus, different planes of sections or the removal of Na+ channel inactivation could not account for the observation. 4. The GABA antagonist bicuculline caused cell firing, mimicking the excitatory effect of DAMGO. Unlike DAMGO, however, bicuculline depolarized PAG cells. 5. Under voltage-clamp conditions, with the same driving force, the evoked inhibitory postsynaptic currents (IPSCs) in these neurons were 2.3 times larger than the evoked excitatory postsynaptic currents (EPSCs). Furthermore, DAMGO inhibited IPSCs by 60.7% while it inhibited EPSCs by 35.3%. 6. We propose that the overall effect of an opioid depends on the dynamic balance of its excitatory and inhibitory actions. In the PAG, the blockade of the inhibitory drive of GABAergic inputs by DAMGO is large. It overcomes the DAMGO-induced hyperpolarization and inhibition of EPSCs and thus results in the excitation of these neurons.

Analgesics, Opioid↗
PubMed2001

Positive modulation of alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) receptors in prefrontal cortical pyramidal neurons by a novel allosteric potentiator.

Positive modulators of glutamate alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) receptors can enhance cognitive function in several species. The present experiments compared the actions of a novel biarylpropylsulfonamide compound, LY404187, with the prototypical benzoylpiperidine, 1-(quinoxalin-6-ylcarbonyl)-piperidine (CX516), on AMPA receptors of prefrontal cortex (PFC) pyramidal neurons. LY404187 (0.03-10 microM) selectively enhanced glutamate-evoked currents through AMPA receptor/channels of acutely isolated pyramidal neurons with considerably greater potency (EC50 = 1.3 +/- 0.3 microM) and efficacy (Emax = 45.3 +/- 8.0-fold increase) than did CX516 (EC50 = 2.8 +/- 0.9 mM; Emax = 4.8 +/- 1.4-fold increase). Both LY404187 and CX516 increased the potency of the glutamate concentration-response profile by 6- and 3-fold, respectively. Rapid perfusion experiments demonstrated that LY404187 produced a marked suppression in the magnitude but no change in the kinetics of receptor desensitization; whereas CX516 produced little change in the degree and a modest deceleration of the desensitization process. In PFC slices, both spontaneous and stimulus-evoked AMPA receptor-mediated excitatory postsynaptic potentials were enhanced by nanomolar concentrations of LY404187. Voltage-sensitive N-methyl-D-aspartate (NMDA) receptor-dependent synaptic responses also were indirectly augmented as a consequence of greater postsynaptic depolarization. Consistent with the in vitro data, LY404187 was 1000-fold more potent than CX516 in enhancing the probability of discharge of PFC neurons in response to stimulation of glutamatergic afferents from hippocampus in vivo. This potentiation by LY404187 was reduced by both selective AMPA (LY300168, 1 mg/kg, i.v.) and NMDA (LY235959, 5 mg/kg, i.v.) receptor antagonists. Collectively, these results demonstrate that LY404187 is an extremely potent and centrally active potentiator of native AMPA receptors and has a unique mechanism of action. The therapeutic implications of AMPA receptor potentiators are discussed.

Allosteric Regulation↗
PubMed2001

Sequence dependence of post-tetanic potentiation after sequential heterosynaptic stimulation in the rat auditory cortex.

1. To investigate the mechanisms for the coding stimulus sequence in the auditory cortex (AC), post-tetanic potentiation (PTP) was recorded after sequentially combined heterosynaptic stimulation was applied in rat AC slices. 2. Brief tetanic stimulation (TS) was applied at two sites on AC slices at intervals of 0.5-10 s. PTP of field potentials was induced by the earlier TS, rather than the later TS. PTP was followed by sequence-dependent long-term potentiation (LTP). 3. Using Ca(2+) imaging in the slices loaded with rhod-2, a Ca(2+) indicator, a sequence-dependent distribution of PTP was found in AC slices. 4. The sequence-dependent PTP in excitatory postsynaptic potentials (EPSPs) was observed in supragranular pyramidal neurons. 5. The sequence dependence of PTP was not significantly affected by 1 microM bicuculline, an antagonist of GABA(A) receptors, or 100 microM 2-hydroxysaclofen, an antagonist of GABA(B) receptors. 6. Depolarization and firing recorded in pyramidal neurons during the later TS were less vigorous than when the slices were incubated in the control medium. However, this suppression of the responses during the later TS was not observed in the presence of 50 microM atropine, an antagonist of muscarinic receptors. 7. PTP was induced by the earlier and later TS in the presence of 50 microM atropine, so that the sequence dependence of PTP was abolished. Pirenzepine (50 microM), an antagonist of muscarinic M1 receptors, but not methoctramine (30 microM), an antagonist of M2 receptors, eliminated the sequence dependence of PTP. 8. These findings suggest that the sequence dependence of PTP in AC might have a role in the temporal processing of auditory information on the scale of seconds.

Animals↗
PubMed1994

Lesion-induced transient suppression of inhibitory function in rat neocortex in vitro.

The structural and functional consequences of a local thermolesion were examined in rat neocortex with electrophysiological in vitro techniques and immunocytochemistry. Age-matched untreated and sham-operated animals served as controls and were analysed in the same way. The lesions consisted of a core of coagulated tissue 2-3 mm in diameter and reached ventrally into the deep cortical layers. After two days reactive astrocytes and after nine days a dense gliosis were observed in the immediate vicinity. Modifications in the intrinsic membrane characteristics and the synaptic network properties were investigated with intra- and extracellular recording techniques after survival times of one to eight days. Neurons recorded in the surrounding of lesions in neocortical slices revealed a significantly more depolarized resting membrane potential and a higher neuronal input resistance. In comparison to cells in control slices, maximal discharge rates to injection of depolarizing current pulses of neurons close to a focal lesion were not significantly altered and intrinsic burst firing was never observed. However, between postlesion days 1 and 5, neurons in the surroundings of lesions showed a transient increase in synaptic excitability. This hyperactivity was most clearly pronounced at a distance of 2-3 mm from the centre of the lesion (i.e. about 1-1.5 mm away from the lesion border) and characterized by long-duration field potential responses and multiphasic long-lasting excitatory postsynaptic potentials to orthodromic stimulation of the afferent input. This lesion-induced hyperexcitability was associated with a significant reduction in the peak conductance of the Cl(-)-dependent fast inhibitory postsynaptic potential and the K(+)-dependent long-latency inhibitory postsynaptic potential, suggesting that the intracortical GABAergic system was functionally impaired. The decrease in synaptic inhibition was associated with prolonged N-methyl-D-aspartate receptor-mediated activity, which could be reversibly blocked by D-amino-phosphonovaleric acid. In addition, neurons recorded in the vicinity of the lesion responded to an orthodromic synaptic stimulus with a long-lasting burst. The lesion-induced disturbance in the balance between the excitatory and inhibitory system may not only have profound influences on the mechanisms of intracortical information processing, but may also lead to the expression of epileptiform activity and long-term functional deficits.

Action Potentials↗
PubMed2001

Inactivation of adenosine A2A receptor impairs long term potentiation in the accumbens nucleus without altering basal synaptic transmission.

The nucleus accumbens is considered to be critically involved in the control of complex motivated behaviors. By modulating its glutamatergic excitatory input, mesolimbic dopaminergic afferents have been implicated in the reinforcing properties of drugs of abuse. However, they might not represent the only path for influencing the accumbens output. The aim of this study was to investigate possible modulation of synaptic transmission at this glutamatergic synapse by adenosine receptors. The standard field potential recording technique was used on brain slices from wild-type and A2A receptor-deficient mice. Neither the stimulus-response relationship nor paired-pulse facilitation was altered in the mutant mice. In both genotypes, the activation of A1 receptors by 2-chloro-N6-cyclopentyladenosine reduced the field excitatory postsynaptic potential (fEPSP) slope to a similar extent. In wild-type slices, activation or blockade of A2A receptors by 2-[4-(carboxyethyl)phenylethylamino]-5'-N-ethylcarboxamidoadenosine and 4-(2-[7-amino-2-(2-furyl)[1,2,4]-triazolo-[2,3-a][1,3,5]triazin-5-ylamino]ethyl)phenol, respectively, did not modify the synaptic transmission. Moreover, a long lasting pre-activation of these A2A receptors did not influence the A1 receptor-mediated reduction in fEPSP slope. Long term potentiation (LTP) of the alpha-amino-3-hydroxy-5-methyl-4-isoxazole proprionate (AMPA) receptor-mediated synaptic transmission could be elicited in both wild-type and A2A receptor-deficient mice. However, LTP appeared to be quantitatively modulated by the A2A receptor pathway since the level of potentiation was reduced in A2A receptor-deficient mice as well as in slices of wild-type mice in which the A2A receptor pathway was blocked. The involvement of the cAMP-dependent protein kinase was supported by the reduction in potentiation level in slices of wild-type mice treated with adenosine 3',5'-cyclic monophosphorothiotate, 8-(4-chlorophenylthio)-Rp isomer, an inhibitor of this enzyme. These data provide evidence that the adenosine acting at the A2A receptor is implicated in events directly or indirectly related to LTP induction in the accumbens whereas it is not involved in the regulation of the basal AMPA receptor-mediated excitatory synaptic transmission.

Animals↗
PubMed1997

Nitric oxide signalling is required for the generation of anoxia-induced long-term potentiation in the hippocampus.

The involvement of nitric oxide in anoxia-induced long-term potentiation (anoxic LTP) of synaptic transmission was investigated in CA1 neurons of rat hippocampal slices using intracellular recording techniques in vitro. In response to superfusion of an anoxic artificial cerebral spinal fluid saturated with 95% N2-5% CO2, the excitatory postsynaptic potential (EPSP) generated in hippocampal CA1 neurons by stimulation of the Schaffer collateral/commissural afferent pathway was completely abolished within 10 min of anoxia. On return to reoxygenated medium, the EPSP returned to the control value within 10 min and was subsequently and progressively potentiated to reach a plateau 15-20 min after return to oxygen. This anoxia-induced persistent increase in synaptic transmission lasted for more than 1 h. Application of the nitric oxide synthase inhibitors 7-nitroindazole (7-NI) or L-N(G)-nitroarginine (NOARG) produced no effects on the baseline EPSP amplitude, but effectively attenuated the anoxic LTP. The inhibitory effects of both 7-NI and NOARG on the anoxic LTP were blocked by L-arginine, a substrate for nitric oxide synthase. These results suggest that nitric oxide is required for the generation of anoxia-induced LTP of glutamatergic synaptic transmission in the CA1 region of the rat hippocampus.

Animals↗
PubMed1999

Interleukin-1beta inhibits a tetraethylammonium-induced synaptic potentiation in the rat dentate gyrus in vitro.

The effect of the pro-inflammatory cytokine, interleukin-1beta on an NMDA receptor-independent form of synaptic plasticity brought about by the application of the K+ channel blocker tetraethylammonium, was examined in the rat dentate gyrus in vitro. Field excitatory postsynaptic potentials (EPSPs) were recorded from the medial perforant path of the dentate gyrus every 20 s. Perfusion of the K+ channel blocker, tetraethylammonium chloride (25 mM) for 10 min and subsequent washout gave rise to robust and long-term potentiation of the field EPSP slope (tetraethylammonium induced long-term potentiation; 125+/-5% of baseline 60 min following tetraethlylammonium-washout; n = 7, P < 0.05) Application of interleukin-1beta (1 ng/ml) for 30 min was found to inhibit the induction, but not the maintenance of the tetraethylammonium induced long-term potentiation (n = 8). Heat denatured interleukin-1beta had no effect on tetraethylammonium induced long-term potentiation (n = 6). The expression of tetraethylammonium induced long-term potentiation was found to be accompanied by an increase in the magnitude of paired pulse depression seen at interstimulus intervals of 20 and 100 ms (controls, 42+/-5% and 13+/-2%; tetraethylammonium, 62+/-5% and 22+/-2% respectively for both intervals; n = 6, P < 0.05). The increase in paired pulse depression at an interstimulus interval of 100 ms was significantly attenuated by pre-treatment of slices with interleukin-1beta. The inhibitory effect of interleukin-1beta on both tetraethylammonium induced long-term potentiation and the tetraethylammonium induced increase in paired pulse depression was antagonised by pre-incubation with the interleukin-1 receptor antagonist. Interleukin-1 receptor antagonist was found to have no effect on tetraethylammonium induced long-term potentiation when applied on its own (n = 5). The p38 mitogen activated protein kinase inhibitor SB203580 (4-(4-fluorophenyl)-2-(4 methylesulfinylphenyl)-5-(4-pyridyl)1H-imidazole) was also found to inhibit the induction of tetraethylammonium induced long-term potentiation (n = 6). These findings suggest a possible role for interleukin-1beta in the modulation of NMDA receptor-independent synaptic plasticity in the rat dentate gyrus.

Animals↗
PubMed2000

Dendrosomatic voltage and charge transfer in rat neocortical pyramidal cells in vitro.

Most excitatory synapses on neocortical pyramidal cells are located on dendrites, which are endowed with a variety of active conductances. The main origin for action potentials is thought to be at the initial segment of the axon, although local regenerative activity can be initiated in the dendrites. The transfer characteristics of synaptic voltage and charge along the dendrite to the soma remains largely unknown, although this is an essential determinant of neural input-output transformations. Here we perform dual whole-cell recordings from layer V pyramidal cells in slices from somatosensory cortex of juvenile rats. Steady-state and sinusoidal current injections are applied to characterize the voltage transfer characteristics of the apical dendrite under resting conditions. Furthermore, dendrosomatic charge and voltage transfer are determined by mimicking synapses via dynamic current-clamping. We find that around rest, the dendrite behaves like a linear cable. The cutoff frequency for somatopetal current transfer is around 4 Hz, i.e., synaptic inputs are heavily low-pass filtered. In agreement with linearity, transfer resistances are reciprocal in opposite directions, and the centroids of the synaptic time course are on the order of the membrane time constant. Transfer of excitatory postsynaptic potential (EPSP) charge, but not peak amplitude, is positively correlated with membrane potential. We conclude that the integrative properties of dendrites in infragranular neocortical pyramidal cells appear to be linear near resting membrane potential. However, at polarized potentials charge transferred is voltage-dependent with a loss of charge at hyperpolarized and a gain of charge at depolarized potentials.

Animals↗
PubMed2001

Morphology, electrophysiology, and calbindin immunoreactivity of myenteric neurons in the guinea pig distal colon.

The morphological and physiological characteristics of myenteric neurons in the guinea pig distal colon were determined using Lucifer yellow- or N-(2-aminoethyl) biotinamide-containing microelectrodes and intracellular recording and staining methods. The neurons in this study (n = 204) were classified on the basis of the shapes of their cell bodies and short processes or dendrites and the number of long processes or axons as Dogiel type I (n = 75 neurons; 36.8%), filamentous (n = 31 neurons; 15.2%), Dogiel type II (n = 38 neurons; 18.6%), and unclassified (n = 60 neurons; 29.4%). All Dogiel type II neurons had action potentials followed by an after-spike hyperpolarization (AH), and most of them (84%) had large, smooth somata and filamentous, short processes in addition to multiple, long processes or axons. Most of Dogiel type I, filamentous, and unclassified neurons (98%) had a single, long process, but four Dogiel type I neurons and one unclassified neuron had two long processes terminating as varicosities within other ganglia or on the surface of longitudinal muscle. The projections of monoaxonal neurons were distributed equally between oral and aboral directions, and most of them received fast excitatory postsynaptic potentials (EPSPs). All of the Dogiel type II neurons and seven Dogiel type I neurons were positive for calbindin immunoreactivity, but three filamentous neurons received fEPSPs, had spikes followed by AH, and were negative for calbindin. The presence of calbindin-immunoreactive(-IR) neurons was quite variable among the ganglia. These results confirm that neither the presence of calbindin immunoreactivity nor the absence of fEPSPs can be used as a predictor of cellular morphology or electrophysiological properties of myenteric neurons in the distal colon.

Action Potentials↗