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PubMed1996

Tonic activation of presynaptic GABA(B) receptors on thalamic sensory afferents.

The presence and role of presynaptic GABA(B) receptors in the control of excitatory amino acid-medicated transmission were investigated (using sharp electrode recordings) in the rat dorsal lateral geniculate nucleus and ventrobasal thalamus in vitro by comparing the effects of the selective GABA(B) receptor agonist, (+ or -)-baclofen, and of two antagonists, CGP 35348 and 2-hydroxy-saclofen, on the excitatory postsynaptic potentials evoked in thalamocortical neurons by stimulation of the sensory afferents. Application of CGP 35348 alone blocked the GABA(B) receptor-mediated inhibitory postsynaptic potential evoked in the dorsal lateral geniculate nucleus by stimulation of the optic tract (n = 5), but had no effect on the resting membrane potential and input resistance of thalamocortical cells (n = 6). In contrast, 2-hydroxy-saclofen caused a hyperpolarization (6.9 + or - 0.5 mV, n = 10) and a decrease in the apparent input resistance (26.3 + or - 2.6%, n = 10). This effect of 2-hydroxy-saclofen was antagonized by CGP 35348. When bicuculline was present in the perfusion medium and following intracellular injection of QX 314, GABA(A) and GABA(B) receptors in the recorded neurons were blocked. Under this condition, application of baclofen decreased the amplitude of the medial lemniscus- and optic tract-evoked excitatory postsynaptic potentials in the two thalamic nuclei investigated. This effect was fully antagonized by CGP 35348 and only partially by 2-hydroxy-saclofen. CGP 35348 alone increased (19.3 + or - 4.3%, n = 5) and 2-hydroxy-saclofen alone decreased (29.9 + or - 8.6%, n = 5) the amplitude of the excitatory postsynaptic potential. This effect of 2-hydroxy-saclofen was not blocked by CGP 35348. These results indicate that presynaptic GABA(B) receptors are present on the terminals of the sensory afferents in the rat dorsal lateral geniculate nucleus and in the ventrobasal thalamus. These receptors are tonically activated by endogenous GABA, at least in vitro, and provide a negative control mechanism by which the excitatory amino acid-mediated transmission within these nuclei can be regulated. In contrast, the endogenous GABA level is not sufficient for a tonic activation of postsynaptic GABA(B) receptors. Furthermore, these results indicate that 2-hydroxy-saclofen acts as a partial agonist on postsynaptic CGP 35348-sensitive GABA(B) receptors, and that, in addition to its antagonist action on presynaptic CGP 35348-sensitive GABA(B) receptors, it also has an effect on either presynaptic, CGP 35348-insensitive GABA(B) receptors and/or another presynaptic receptor type.

Animals↗
PubMed2000

Effects of the potent ampakine CX614 on hippocampal and recombinant AMPA receptors: interactions with cyclothiazide and GYKI 52466.

R,S-alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor up-modulators of the benzamide type ("ampakines") have previously been shown to enhance excitatory synaptic transmission in vivo and in vitro and AMPA receptor currents in excised patches. The present study analyzed the effects of an ampakine (CX614; 2H,3H, 6aH-pyrrolidino[2",1"-3',2']1,3-oxazino[6',5'-5,4]benz o[e]1, 4-dioxan-10-one) that belongs to a benzoxazine subgroup characterized by greater structural rigidity and higher potency. CX614 enhanced the size (amplitude and duration) of field excitatory postsynaptic potentials in hippocampal slices and autaptically evoked excitatory postsynaptic currents in neuronal cultures with EC(50) values of 20 to 40 microM. The compound blocked desensitization (EC(50) = 44 microM) and slowed deactivation of responses to glutamate by a factor of 8.4 in excised patches. Currents through homomeric, recombinant AMPA receptors were enhanced with EC(50) values that did not differ greatly across GluR1-3 flop subunits (19-37 microM) but revealed slightly lower potency at corresponding flip variants. Competition experiments using modulation of [(3)H]fluorowillardiine binding suggested that CX614 and cyclothiazide share a common binding site but cyclothiazide seems to bind to an additional site not recognized by the ampakine. CX614 did not reverse the effect of GYKI 52466 on responses to brief glutamate pulses, which indicates that they act through separate sites, a conclusion that was confirmed in binding experiments. In sum, these results extend prior evidence that ampakines are effective in enhancing synaptic responses, most likely by slowing deactivation, and that their effects are exerted through sites that are only in part shared with other modulators.

Alanine↗
PubMed1996

Electrophysiological elucidation of pathways of intrinsic horizontal connections in rat visual cortex.

Cortical neurons receive synaptic inputs through both vertical and horizontal pathways. We made a systematic survey of the synaptic strength and intracortical pathways of intrinsic horizontal connections in rat visual cortex using intracellular recordings from alice preparations. Excitatory postsynaptic potentials were recorded from pyramidal neurons of layers 2/3 and layers 5/6 in response to electrical shocks applied to these layers at a lateral distance of 1.0 mm from the impaled neuron or to the underlying white matter. When the threshold intensity of stimulation to activate monosynaptic excitatory postsynaptic potentials was compared, the vertical input had a lower threshold than the horizontal inputs. The threshold intensity of the horizontal inputs was lower, and the amplitude of the responses was larger in sagittally sectioned slices than in coronal slices, suggesting that the horizontal synaptic connection in the rat visual cortex was stronger in the rostrocaudal than in the mediolateral direction. Tetrodotoxin puffs focally applied to gray matter between the stimulation and the recording sites caused a transient depression of excitatory postsynaptic potentials, which was selective to the input conveyed through the puffed area. This pharmacological dissection revealed that routes parallel to the cortical Iaminae in the same layer as the stimulation site mediated the largest part of excitation conduction of intrinsic connections. Obliquely ascending routes mediated almost half of all the detected inputs originating from a deep layer to the neurons in either layers 5/6 or layers 2/3, whereas the contribution of obliquely descending routes from layers 2/3 to layers 5/6 was small (25%). Our results present semi-quantitative data on the connection diagram of the intrinsic neuronal circuits in the rat visual cortex, which will provide the basis for further investigations of the roles of the intrinsic connections in information processing in rodent cerebral cortex.

Action Potentials↗
PubMed2005

Sevoflurane blocks cholinergic synaptic transmission postsynaptically but does not affect short-term potentiation.

BACKGROUND: As compared with their effects on both inhibitory and excitatory synapses, little is known about the mechanisms by which general anesthetics affect synaptic plasticity that forms the basis for learning and memory at the cellular level. To test whether clinically relevant concentrations of sevoflurane affect short-term potentiation involving cholinergic synaptic transmission, the soma-soma synapses between identified, postsynaptic neurons were used. METHODS: Uniquely identifiable neurons visceral dorsal 4 (presynaptic) and left pedal dorsal 1 (postsynaptic) of the mollusk Lymnaea stagnalis were isolated from the intact ganglion and paired overnight in a soma-soma configuration. Simultaneous intracellular recordings coupled with fluorescent imaging of the FM1-43 dye were made in either the absence or the presence of sevoflurane. RESULTS: Cholinergic synapses, similar to those observed in vivo, developed between the neurons, and the synaptic transmission exhibited classic short-term, posttetanic potentiation. Action potential-induced (visceral dorsal 4), 1:1 excitatory postsynaptic potentials were reversibly and significantly suppressed by sevoflurane in a concentration-dependent manner. Fluorescent imaging with the dye FM1-43 revealed that sevoflurane did not affect presynaptic exocytosis or endocytosis; instead, postsynaptic nicotinic acetylcholine receptors were blocked in a concentration-dependent manner. To test the hypothesis that sevoflurane affects short-term potentiation, a posttetanic potentiation paradigm was used, and synaptic transmission was examined in either the presence or the absence of sevoflurane. Although 1.5% sevoflurane significantly reduced synaptic transmission between the paired cells, it did not affect the formation or retention of posttetanic potentiation at this synapse. CONCLUSIONS: This study demonstrates that sevoflurane blocks cholinergic synaptic transmission postsynaptically but does not affect short-term synaptic plasticity at the visceral dorsal 4-left pedal dorsal 1 synapse.

Anesthetics, Inhalation↗
PubMed1982

Calcium-induced long-term potentiation in the hippocampus.

The effect of a transient increase in extracellular calcium concentration on the Schaffer collateral-commissural evoked excitatory postsynaptic potential and population spike responses of CAI pyramidal neurons was investigated using the rat in vitro hippocampal slice preparation. Brief exposure of slices (5-10 min) to twice the normal concentration of calcium (4 mM) induced a marked potentiation of both the excitatory postsynaptic potential and population spike that could persist for at least 3 h. No long-term changes were observed in either the presynaptic fiber volley of antidromically evoked CAI population spike, indicating that the potentiation could not be attributed to an increase in the number of fibers activated or a generalized increase in cellular excitability. The response of CAI pyramidal neurons to the iontophoretic application of L-glutamate in the apical dendritic zone was also unaffected after exposure to high calcium perfusate, suggesting a lack of alteration in membrane excitability or receptor sensitivity restricted to the region of synaptic input. In addition, total intracellular calcium content of individual slices, measured by atomic absorption spectrophotometry, was significantly increased for at least 1 h following return to the control medium. These data indicate that brief exposure of in vitro hippocampal slices to a high extracellular calcium concentration results in a long-term increase in synaptic efficacy which is similar in many respects to long-term potentiation induced by tetanic stimulation of hippocampal excitatory afferents. The results further suggest that the mechanisms underlying calcium-induced long-term potentiation may reside in presynaptic components and involve an enhanced transmitter release.

Afferent Pathways↗
PubMed1995

Pre- and postsynaptic whole-cell recordings in the medial nucleus of the trapezoid body of the rat.

1. Simultaneous whole-cell recordings in a rat brain slice preparation are described from presynaptic terminals (calyces of Held) and postsynaptic somata which form an axosomatic synapse in the medial nucleus of the trapezoid body (MNTB). 2. Presynaptic action potentials evoked suprathreshold excitatory postsynaptic potentials (EPSPs). The minimum synaptic delay was around 0.4 ms at 36 degrees C and 0.9 ms at 23-24 degrees C. The amplitude of the L-alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionate (AMPA) receptor-mediated component of the excitatory postsynaptic currents (EPSCs) was 2-13 nA (at -80 mV). 3. Current-voltage relations showed that presynaptic Ca2+ channels were of the high voltage-activated type. 4. A single action potential evoked a presynaptic fluorescence transient that decayed with a time constant of 0.3-0.7 s, depending on the concentration (60-200 microM) of the Ca2+ indicator Calcium Green-5N (CG-5N). The peak amplitude of the [Ca2+]i transient was severalfold larger in the terminal than in the preterminal axon. 5. EPSC peak amplitudes were stable for more than 30 min after establishing the whole-cell configuration in the presynaptic terminal when the pipette contained 50 microM BAPTA. In contrast, with 1 mM BAPTA, peak amplitudes of EPSCs were reduced to one-third. 6. Trains of presynaptic action potentials evoked EPSCs with progressively smaller amplitudes. Little change was observed in the depression when the terminals were dialysed with 50 microM BAPTA, whereas depression was reduced with 1 mM BAPTA. 7. In low (1 mM) [Ca2+]o, facilitation instead of depression of EPSCs was observed. 8. The effects of presynaptic BAPTA suggest that the endogenous mobile Ca2+ buffer capacity of giant presynaptic terminals in the MNTB is lower than in other terminals of fast transmitting synapses.

Action Potentials↗
PubMed1981

Effects of opioid peptides on synaptic potentials in explants of rat hippocampus.

Bath application of 10(-8) M FK 33-824 (an enkephalin analogue) and 10(-7) M beta-endorphin reversibly induced stimulus-evoked bursting activity with depolarization shifts in cultured hippocampal pyramidal cells. Statistical analysis of the data revealed that in the majority of cells, inhibitory postsynaptic potentials were markedly decreased and excitatory postsynaptic potentials increased prior to the development of bursting activity, although some inhibition persisted in cells exposed to opioid peptides. In a minority of cells, no alteration in synaptic potentials were observed to precede the stimulus-evoked bursts induced by the opioid peptides.

Action Potentials↗
PubMed1994

Responses of CA1 pyramidal neurons in rat hippocampus to transient forebrain ischemia: an in vivo intracellular recording study.

The electrophysiological responses of CA1 pyramidal neurons to 5 min forebrain ischemia were studied with intracellular recording and staining techniques in vivo. The baseline membrane potential rapidly depolarized to approximately -20 mV about 3 min after the onset of ischemia and began to repolarize 1-3 min after recirculation. The amplitude of this ischemic depolarization (ID) was related directly to the severity of ischemia and its latency of onset was inversely related to brain temperature. Spontaneous synaptic activity ceased shortly after ischemia onset while the evoke synaptic potentials lasted until shortly before the onset of ID. Inhibitory postsynaptic potentials (IPSPs) disappeared earlier than excitatory postsynaptic potentials (EPSPs) and the membrane input resistance of CA1 neurons increased after the onset of ischemia.

Action Potentials↗
PubMed2003

Increased dendritic excitability in hippocampal ca1 in vivo in the kainic acid model of temporal lobe epilepsy: a study using current source density analysis.

We used kainic acid in rats as an animal model of temporal lobe epilepsy, and studied the synaptic transmission in hippocampal subfield CA1 of urethane-anesthetized rats in vivo. Dendritic currents were revealed by field potential mapping, using a single micropipette or a 16-channel silicon probe, followed by current source density analysis. We found that the population excitatory postsynaptic potentials in the basal dendrites and distal apical dendrites of CA1 were increased in kainate-treated as compared with control rats following paired-pulse, but not single-pulse, stimulation of CA3b or medial perforant path. In contrast, the trisynaptic midapical dendritic response in CA1 following medial perforant path stimulation was decreased in kainate-treated as compared with control rats. Increased coupling between excitatory postsynaptic potential and the population spike in CA1 was found after kainate seizures. Short-latency, presumably monosynaptic CA1 population spikes following medial perforant path stimulation was found in kainate-treated but not control rats. An enhancement of dendritic excitability was evidenced by population spikes that invaded into or originated from the distal apical dendrites of CA1 in kainate-treated but not control rats. Reverberation of hippocampo-entorhinal activity was evidenced by recurrent excitation of CA1 following CA3b stimulation in kainate-treated but not control rats. Blockade of inhibition by intraventricularly administered bicuculline induced excitatory potentials in CA1 that were stronger and more prolonged in kainate-treated than control rats. The bicuculline-induced excitation was mainly blocked by non-N-methyl-D-aspartate receptor antagonists. We conclude that kainate seizures induced disinhibition in CA1 that unveiled excitation at the basal and distal apical dendrites, resulting in enhancement of the direct entorhinal cortex to CA1 input and reverberations via the hippocampo-entorhinal loop. These changes in the output of the hippocampus from CA1 are likely detrimental to the behavioral functions of the hippocampus and they may contribute to increased seizure susceptibility after kainate seizures.

Action Potentials↗
PubMed1998

Duration of NMDA-dependent synaptic potentiation in piriform cortex in vivo is increased after epileptiform bursting.

Stimulation of afferent fibers with current pulse trains has been reported to induce long-term potentiation (LTP) in piriform cortex in vitro but not in vivo. LTP has been observed in vivo only when trains are paired with behavioral reinforcement and as a consequence of kindled epileptogenesis. This study was undertaken in the urethan-anesthetized rat to determine if the reported failures to observe pulse-train evoked LTP in vivo may be related to a lesser persistence rather than lack of occurrence, if disinhibition might facilitate induction, and to examine the nature of the relationship between seizure activity and LTP. Stimulation of afferent fibers in the lateral olfactory tract with theta-burst trains under control conditions potentiated the monosynaptic field excitatory postsynaptic potential (EPSP) by approximately the same extent (20.3 +/- 2%; n = 12) as reported for the slice. However, in contrast to the slice, potentiation in vivo decayed to a low level within 1-2 h after induction (70% loss in 1.5 h, on average). The N-methyl--aspartate (NMDA)-receptor antagonists -APV and MK-801 blocked the induction of this decremental potentiation. Pharmacological reduction of gamma-aminobutyric acid-mediated inhibition at the recording site did not increase the duration of potentiation. In contrast, theta-burst stimulation applied after recovery from a period of epileptiform bursting induced stable NMDA-dependent potentiation. Mean increase in the population EPSP was approximately the same as under control conditions (21 +/- 2%; n = 6), but in five of six experiments there was little or no decay in potentiation for the duration of the monitoring period (</=6 h). It is concluded that seizure activity has an enabling action on the induction of persistent synaptic potentiation by stimulus trains that bypasses the need for behavioral reinforcement.

2-Amino-5-phosphonovalerate↗
PubMed1997

Activation of interneurons at the stratum oriens/alveus border suppresses excitatory transmission to apical dendrites in the CA1 area of the mouse hippocampus.

The consequences of activation or inactivation of interneurons at the CA1 stratum oriens/ alveus border for signal transmission at the apical dendritic region of pyramidal cells were investigated in slices from mice submerged in a perfusion chamber. A characteristic subpopulation of interneurons with a horizontal dendritic tree in this region, which sends a GABAergic projection to the apical dendrites of CA1 pyramidal cells is strongly excited by metabotropic glutamate receptor activation and receives GABAergic input from vasoactive intestinal polypeptide-containing interneurons. Pressure ejection of glutamate or the metabotropic agonist 1s,3r-aminocyclopentane dicarboxylic acid from micropipettes onto the stratum oriens/alveus border caused a long lasting (more than 90 min) decrease of field-excitatory postsynaptic potentials in the strata radiatum and lacunosum-moleculare. The GABAB antagonist CGP 35348 (100 microM in the perfusion fluid) partially and reversibly blocked this effect. Vasoactive intestinal polypeptide- (0.1 microM in the bath) excited neurons with response and firing properties characteristic for interneurons at the oriens/alveus border. Local pressure application of vasoactive intestinal polypeptide (10 microM) to the alveus region led, after a brief (2 min) and small (10%) increase, to a longer lasting (30-50 min) decrease (by 20-30%) in the slope of the field-excitatory postsynaptic potential in strata radiatum and lacunosum-moleculare. This action was completely blocked by bath application of CGP 35348. Local application of tetrodotoxin in the stratum oriens/alveus region markedly increased the slope of evoked dendritic excitatory postsynaptic potentials, and caused multiple firing of pyramidal cells. Thus, stratum oriens/alveus interneurons have a profound inhibitory effect on signal transmission in the apical dendritic area of CA1, which is, at least in part, mediated by GABAB receptors. It appears that the GABAB receptor-mediated effect in stratum lacunosum-moleculare is produced by vasoactive intestinal polypeptide-sensitive interneurons.

Animals↗
PubMed2000

Ethanol inhibition of N-methyl-D-aspartate responses involves presynaptic gamma-aminobutyric acid(B) receptors.

Ethanol alters N-methyl-D-aspartate (NMDA) and gamma-aminobutyric acid subtype A (GABA(A)) receptor-mediated neurotransmission. We have previously demonstrated that GABA(B) receptor blockade uncovers ethanol enhancement of GABA(A) responses in the hippocampus. Therefore, we evaluated in vivo and in vitro the role of GABA(B) receptors in ethanol-induced inhibition of neuronal activity as well as NMDA responses in the hippocampus, ventral tegmental area (VTA), and nucleus accumbens (NAcc), three brain areas with known sensitivity to low doses of ethanol. In vivo, in situ microelectrophoretic application of ethanol enhanced inhibition of VTA GABA neuron firing rate by the GABA(B) agonist baclofen and reduced inhibition of VTA GABA firing rate by the GABA(A) agonist muscimol. The GABA(B) antagonist CGP35348 blocked baclofen- and ethanol-induced, but not muscimol-induced, reduction of NMDA-activated firing of hippocampal hilar mossy cells, hilar interneurons, and VTA GABA neurons, as well as ethanol inhibition of NMDA receptor-sensitive, amygdala-driven NAcc neurons. We performed in vitro studies in NAcc slices to evaluate the mechanism of GABA(B) receptor-mediated ethanol inhibition of NMDA neurotransmission. In the presence of the non-NMDA receptor antagonist 6-cyano-7-nitroquinoxaline-2,3-dione and the GABA(A) receptor antagonist bicuculline, superfusion of the GABA(B) antagonist CGP55845 blocked ethanol (66 mM) inhibition of evoked NMDA receptor-mediated excitatory postsynaptic potentials. However, CGP55845 did not significantly affect ethanol inhibition of NMDA currents produced by pressure application of NMDA or non-NMDA glutamatergic excitatory postsynaptic potentials evoked in the presence of the bicuculline and the NMDA antagonist DL-2-amino-5-phosphonovalerate. Taken together, these findings suggest that the sensitivity of NMDA receptor-mediated neurotransmission to ethanol is regulated by GABA(B) receptors, possibly at presynaptic sites.

Amygdala↗
PubMed1997

Cyclic changes in NMDA receptor activation in hippocampal CA1 neurons after ischemia.

We studied N-methyl-D-aspartate (NMDA) receptor-mediated synaptic potentials in CA1 pyramidal neurons using hippocampal slices of gerbils after transient forebrain ischemia. In the presence of 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX) and bicuculline, stimulation of Schaffer collateral/commissural fibers induced field excitatory postsynaptic potentials (fEPSP) activated by NMDA receptors. We found that in many slices after ischemia, prolonged low-frequency stimulation (0.1-10 Hz) caused repeated depression and potentiation of the NMDA-mediated fEPSP. Changes in fEPSP amplitude were dependent on stimulus frequency and the cycle frequency ranged from 0.08 to 2.5 cycles/min. These cyclic changes were blocked by application of BAPTA-AM, a membrane-permeable Ca2+ chelator, but were little affected by application of verapamil or by lowering the Ca2+ in bathing solution. Intracellular recordings from CA1 neurons revealed that low-frequency stimulation caused periodic depolarizations of membrane potential accompanied by depression of the excitatory postsynaptic potentials. The cyclic changes of fEPSPs were blocked by inhibitors of protein kinase C (PKC) but were unaffected by inhibitors of Ca2+/calmodulin-dependent protein kinase II (CaMKII) or myosin light-chain kinase (MLCK). These results suggest that stimulus-dependent NMDA-receptor activation, mediated by PKC, takes place in the postischemic CA1 neurons and that the cyclic change may reflect abnormal intracellular Ca2+ signaling processes leading to neuronal degeneration.

Animals↗
PubMed2003

Long-term potentiation and long-term depression in hippocampal CA1 neurons of mice lacking the IP(3) type 1 receptor.

To investigate the role in synaptic plasticity of Ca(2+) released from intracellular Ca(2+) stores, mice lacking the inositol 1,4,5-trisphosphate type 1 receptor were developed and the physiological properties, long-term potentiation, and long-term depression of their hippocampal CA1 neurons were examined. There were no significant differences in basic synaptic functions, such as membrane properties and the input/output relationship, between homozygote mutant and wild-type mice. Enhanced paired-pulse facilitation at interpulse intervals of less than 60 ms and enhanced post-tetanic potentiation were observed in the mutant mice, suggesting that the presynaptic mechanism was altered by the absence of the inositol 1,4,5-trisphosphate type 1 receptor. Long-term potentiation in the field-excitatory postsynaptic potentials induced by tetanus (100 Hz, 1 s) and the excitatory postsynaptic currents induced by paired stimulation in hippocampal CA1 pyramidal neurons under whole-cell clamp conditions were significantly greater in mutant mice than in wild-type mice. Homosynaptic long-term depression of CA1 synaptic responses induced by low-frequency stimulation (1 Hz, 500 pulses) was not significantly different, but heterosynaptic depression of the non-associated pathway induced by tetanus was blocked in the mutant mice. Both long-term potentiation and long-term depression in mutant mice were completely dependent on N-methyl-D-aspartate receptor activity. To rule out the possibility of an effect compensating for the lack of the inositol 1,4,5-trisphosphate type 1 receptor occurring during development, an anti-inositol 1,4,5-trisphosphate type 1 receptor monoclonal antibody that blocks receptor function was diffused into the wild-type cell through a patch pipette, and the effect of acute block of inositol 1,4,5-trisphosphate type 1 receptor on long-term potentiation was examined. Significant enhancement of long-term potentiation was observed compared with after control immunoglobulin G injection, suggesting that developmental redundancy was not responsible for the increase in long-term potentiation amplitude observed in the mutant mouse. The properties of channels that could be involved in long-term potentiation induction were examined using whole-cell recording. N-methyl-D-aspartate currents were significantly larger in mutant mice than in wild-type mice only between holding potentials of -60 and -80 mV. We conclude that inositol 1,4,5-trisphosphate type 1 receptor activity is not essential for the induction of synaptic plasticity in hippocampal CA1 neurons, but appears to negatively regulate long-term potentiation induction by mild modulation of channel activities.

Action Potentials↗
PubMed2000

Blockade by pertussis toxin of the opioid effect on guinea pig ileum. Contractility and electrophysiological neuronal recording.

The aim of the present study was to analyse the correlation between functional and electrophysiological effects of the opioids in guinea pig ileum. Preparations of guinea pig ileum myenteric plexus-longitudinal muscle strips were used to compare the effect of two opioids, morphine (a mu-agonist) and U-50,488H (a kappa-agonist) on the electrically-induced contractile response and the excitatory postsynaptic potentials exhibited by the myenteric neurones when the internodal strands are electrically stimulated. Both opioids dose-dependently inhibited the contractile responses and the fast excitatory postsynaptic potentials (fEPSPs) in S neurones but did not modify the amplitude of the slow postsynaptic potentials. Pertussis toxin pretreatment was able to antagonise the effects of both morphine and U-50,448H. From our results it can be suggested that the effect of the opioids on guinea pig ileum involves the inhibition of neuronal fEPSPs.

3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cycloh↗
PubMed2004

HIV secreted protein Tat prevents long-term potentiation in the hippocampal CA1 region.

HIV-associated dementia (HAD) is a complication of advanced HIV disease. Both viral products and host cytokines are believed to be involved in the pathogenesis of HIV-associated neurological manifestations. Among the viral products released by HIV-infected cells is the soluble protein Tat. We investigated the effect of exposure of organotypic hippocampal slices to 100 nM recombinant Tat 1-86 on long-term potentiation (LTP) of field excitatory postsynaptic potential (fEPSP) at Schaffer collateral/commissural fiber-CA1 synapses. Exposure to Tat 1-86 prevented the induction of LTP without affecting post-tetanic potentiation. Tat 1-72delta31-61, which lacks the neurotoxic domain of Tat, had no significant effect on LTP. Tat's ability to disrupt synaptic plasticity may be relevant to the pathogenesis of the cognitive impairments seen in patients with HIV disease.

Animals↗
PubMed2007

Developmental differences in neuromodulation and synaptic properties in the lamprey spinal cord.

Functional properties in the spinal cord change during development to adapt motor outputs to differing behavioral requirements. Here, we have examined whether there are also developmental differences in spinal cord plasticity by comparing the neuromodulatory effects of substance P in the larval lamprey spinal cord with its previously characterized effects in premigratory adults. The premigratory adult effects of substance P were all significantly reduced in larvae. As the adult effects of substance P depend on the N-methyl-d-aspartate (NMDA)-dependent potentiation of glutamatergic synaptic transmission, we examined if the developmental differences in neuromodulation were associated with differences in synaptic properties. We found that the amplitude, rise time, and half-width of excitatory postsynaptic potentials (EPSPs) from excitatory network interneurons were all significantly reduced in larvae compared with adults. These differences were associated with a reduction in the NMDA component of larval EPSPs, an effect that could have contributed to the reduced modulatory effects of substance P in larvae. In contrast to glutamatergic inputs, the amplitude, rise time, and half-width of inhibitory postsynaptic potentials (IPSPs) from ipsilateral inhibitory interneurons were all significantly increased in larvae compared with adults. Substance P also potentiated larval IPSP amplitudes, an effect not seen in adults. This increase in inhibition contributed to the reduced effects of substance P in larvae, as premigratory adult-like modulation could be evoked when inhibition was blocked with strychnine. These results suggest that opposite developmental changes in excitatory and inhibitory synaptic transmission and their modulation are associated with developmental differences in spinal cord neuromodulation.

Age Factors↗
PubMed2002

Differences in the corticospinal projection from primary motor cortex and supplementary motor area to macaque upper limb motoneurons: an anatomical and electrophysiological study.

To further our understanding of the functional roles of different motor cortical areas, we made a quantitative comparison of the density of corticospinal projections from primary motor cortex (M1) and supplementary motor area (SMA) to spinal motor nuclei supplying hand and finger muscles in four macaque monkeys. We also compared the action of corticospinal outputs excited by electrical stimulation of these two areas on upper limb motoneurons recorded in three anaesthetized macaques. The hand representations of SMA and M1 were first identified using structural magnetic resonance imaging scans and intracortical microstimulation. In the anatomical study we then made focal injections of wheatgerm agglutinin- horseradish peroxidase into these representations, which were subsequently confirmed by analysis of retrograde cortical labelling. Densitometric analysis showed that corticospinal projections from M1 were denser and occupied a greater proportion of the hand muscle motor nuclei than did projections from SMA. In caudal Th1 the densest projections from M1 occupied 81% of this motoneuronal area, compared with only 6% from SMA. In the electrophysiological study, bipolar intracortical stimulation of the hand representation of M1 and SMA evoked direct (D) and indirect (I) corticospinal volleys. Volleys elicited by M1 stimulation had larger amplitudes and faster conduction velocities than those evoked from the SMA. Intracellular recordings were made from 84 contralateral upper limb motoneurons. M1 and SMA stimulation evoked markedly different responses in tested motoneurons: EPSPs were larger and more common from M1 (88% of motoneurons) than from SMA (48%). Some motoneurons (16/84) showed evidence of excitatory postsynaptic potentials mediated by monosynaptic action of the D-wave evoked from M1; these early effects were not observed from the SMA. In most motoneurons (74/84) EPSPs had segmental latencies indicating that they were due to monosynaptic action of the I-wave. The results are consistent with cortico-motoneuronal (CM) connections originating from both SMA and M1 converging upon single motoneurons, but those from M1 are far more numerous and exert stronger excitatory effects than from the SMA. Thus although they may function in parallel, the two CM projections probably make different contributions to upper limb motor control.

Animals↗