Polysynaptic Excitatory Postsynaptic Potentials Research Articles

Dopaminergic modulation of spinal neurons and synaptic potentials in the lamprey spinal cord.

It has been shown previously that dopamine-immunoreactive cells and processes are present in the lamprey spinal cord and that dopamine modulates the cycle period of fictive swimming. The present study was undertaken to further characterize the effects of dopamine on the cellular properties of lamprey spinal neurons and on inhibitory and excitatory postsynaptic potentials to determine how dopaminergic modulation may affect the central pattern generator for locomotion. Dopamine reduced the late afterhyperpolarization (late AHP) following the action potential of motoneurons, and in three types of sensory neurons: dorsal cells, edge cells, and giant interneurons. The late AHP was not reduced in lateral interneurons or CC interneurons, both of which are part of the central motor pattern generating neural network. The reduction of the late AHP in motoneurons, edge cells, and giant interneurons resulted in an increase in firing frequency in response to depolarizing current injection. In the six cell classes examined, no changes were observed in the resting membrane potential, input resistance, rheobase, spike amplitude, or spike duration after application of dopamine. The durations of action potentials broadened by application of tetraethylammonium in motoneurons and of calcium action potentials in dorsal cells and giant interneurons were decreased after bath application of 10 microM dopamine. The durations of tetrodotoxin-resistant, N-methyl-D-aspartate-induced membrane potential oscillations in lamprey spinal motoneurons were increased after bath application of 1-100 microM dopamine, due perhaps to reduced calcium entry and thus reduced Ca(2+)-dependent K+ current responsible for the repolarization of the membrane potential during each oscillation. Polysynaptic inhibitory postsynaptic potentials (IPSPs) elicited in lamprey spinal motoneurons by stimulation of the contralateral half of the spinal cord were reduced by bath application of 10 microM dopamine. Polysynaptic excitatory postsynaptic potentials were not reduced by dopamine. Monosynaptic IPSPs in motoneurons elicited by stimulation of single contralateral inhibitory CC interneurons and single ipsilateral axons were reduced by bath application of dopamine (10 microM). Monosynaptic IPSPs in CC interneurons elicited by stimulation of ipsilateral lateral interneurons, however, showed no change after application of dopamine. The lack of dopaminergic effect on the late AHP of the locomotor network neurons, lateral interneurons and CC interneurons, and the selective reduction of IPSPs from CC interneurons suggest that synaptic modulation may play an important role in dopaminergic modulation of cycle period during fictive swimming in the lamprey.

Maturation in properties of motoneurons and their segmental input in the neonatal rat.

1. The isolated neonatal rat spinal chord preparation was used to investigate the development of segmental afferent input to lumbar motoneourons during the first nine postnatal days. Motoneurons, identified with the use of antidromic stimulation of the ventral roots, were characterized electrophysiologically, and their synaptic input in response to stimulation of the homologous dorsal root was studied. 2. Motoneurons in postnatal day (P) 1-3 preparations exhibited lower rheobase and lower input conductance than those impaled in spinal cords taken from animals at P7-9. This finding is consistent with the increase in motoneuron size known to occur during this time. 3. Monosynaptic excitatory postsynaptic potentials (EPSPs) evoked at low-frequency (0.1-Hz) stimulation in high-Ca2+ saline exhibited no change in mean amplitude between P1-3 and P7-9 despite an increase in input conductance of the motoneurons, suggesting that some aspect of these synapses underwent a compensatory change. Polysynaptic EPSPs were smaller in the older animals. 4. When bursts of stimuli were delivered at higher frequencies ranging from 10 to 167 Hz, the EPSPs exhibited substantial depression. The depression of monosynaptic EPSPs was significantly less at P7-9 than at P1-3. Changing the bathing solution from a high-Ca2+ saline to a low-Ca2+/high-Mg2+ saline reduced the amplitude of the monosynaptic EPSP and made it less susceptible to depression during high-frequency stimulation. Facilitation of the evoked response, which has been observed in the adult rat, was never seen under any of these conditions. 5. Although synapses on high-rheobase motoneurons exhibited less depression than those on low-rheobase motoneurons, as anticipated from previous results in adults, the EPSPs at synapses on high-rheobase motoneurons tended to be larger in amplitude, not smaller as expected. This suggests that the specialization among synapses on motoneurons that exists in adults has not yet developed by P7-9. Instead, EPSP amplitude may be greater in motoneurons that have been growing rapidly, such as the high-rheobase motoneurons found during these stages of development. 6. Evidence is presented that the growing diversity shown in modulation behavior at the Ia afferent motoneuron synapse during the first postnatal week is determined primarily by motoneuron characteristics. It is speculated that as motoneurons grow during the immediate postnatal period, the presynaptic terminal regions of axons terminating on them become specialized to render the synapse less susceptible to depression. This specialization may be myelination of the afferent terminals or may perhaps be related to the transmitter release process itself. The adult distribution of depression develops later, presumably as the components of the monosynaptic reflex mature.

Role of protein synthesis in the transition from synaptic short-term to long-term depression in neurons of Helix pomatia.

The time course of the formation of synaptic long-term depression was analysed in neurons of Helix pomatia. Polysynaptic excitatory postsynaptic potentials were evoked in identified neurons by stimulation of the right pallial nerve. First, synaptic depression was observed during four consecutive series of excitatory postsynaptic potentials spaced by either 2, 10 or 60 min in the presence and absence of compounds inhibiting protein synthesis. Inhibition of RNA translation (but not of transcription) reduced the increasing depression of series spaced by 10 and 60 min but not by 2 min. This demonstration of translation-dependent depression present only 10 min after a previous excitatory postsynaptic potential series was analysed further by observations of the time course of excitatory postsynaptic potential recovery from short-term depression in experiments with intact versus inhibited protein synthesis. When synthesis was inhibited, recovery occurred along a double-exponential trajectory. However, when synthesis was intact, the exponential recovery was interrupted discontinuously 6-10 min after a series of excitatory postsynaptic potentials by the onset of a spontaneous and increasing depression lasting for at least 12 h. Puromycin, anisomycin and actinomycin D were used as inhibitors not affecting the short-term properties of excitatory postsynaptic potentials. Experiments with camptothecin, on the other hand, revealed that this inhibitor enhanced excitatory postsynaptic potential amplitudes and reduced their short-term depression. It is concluded that long-term depression, depending upon de novo protein synthesis, was initiated only 10 min after a series of excitatory postsynaptic potentials. Evidence was obtained indicating that this early initiated protein synthesis circumvented the transcription processes within the cell nuclei.

Depth electrode studies and intracellular dentate granule cell recordings in temporal lobe epilepsy

Hippocampal depth electrodes are often used to localize seizure onset in patients who may have temporal lobe epilepsy (TLE). A number of features of the spontaneous seizures and of their ictal onset patterns can be analyzed from these recordings. We compared a number of the typical electroencephalographic (EEG) changes at seizure onset with several cellular parameters recorded in dentate granule cells from the same 14 patients diagnosed with medial temporal sclerosis (MTS) to examine the pathophysiological correlates of this spontaneous EEG activity in this form of TLE. The intracellularly recorded parameters include the propensity to fire evoked epileptiform bursts, the absence of evoked inhibitory potentials, the presence of polysynaptic excitatory postsynaptic potentials, and the presence of spontaneous excitatory activity. We noted several correlations between the EEG data and the intracellular recordings. The absence of synaptically evoked bursts was correlated with the presence of low-voltage fast activity at seizure onset. In addition, the loss of inhibitory postsynaptic potentials was correlated with the presence of periodic spiking pre-ictally. Several other correlations were also noted. These data indicate that EEG findings may be predictive of anatomical and cellular pathological changes and provide clues to the physiological mechanisms involved in this form of epilepsy.

Kappa-opioid receptor agonists modulate excitatory transmission in substantia gelatinosa neurons of the rat spinal cord

This study examined the effects of selective activation of kappa 1-opioid receptors on excitatory transmission in substantia gelatinosa (SG) using intracellular recordings from SG neurons in transverse slices of the young rat lumbar spinal cord. Monosynaptic and polysynaptic excitatory postsynaptic potentials (EPSPs) were evoked by orthodromic electrical stimulation of A delta or C primary afferent fibers in the dorsal root after blocking inhibitory inputs with bicuculline and strychnine, NMDA receptors with D-2-amino-5-phosphonovaleric acid and mu- and delta-opioid receptors with CTAP and ICI 174,864, respectively. Bath application of dynorphin A1-17 or U-69, 593 caused dual modulation of the peak amplitude of presumed monosynaptic AMPA receptor-mediated EPSPs, decreasing synaptic potentials at nanomolar concentrations in a majority of SG cells examined (dynorphin, 63%; U-69,593, 91%), and increasing EPSPs at micromolar concentrations. Only the inhibitory action of dynorphin A1-17 was consistently and completely blocked by norbinaltorphimine (nor-BNI). Since U-69,593 and nor-BNI are selective for the kappa 1-opioid receptors, the depression of EPSPs is likely to be mediated by the kappa1-opioid receptors. Under conditions of blockade of synaptic transmission with TTX and mu-and delta-opioid receptors, dynorphin A1-17 and U-69,593 hyperpolarize most of SG neurons and decrease their membrane input resistance, the finding suggesting that direct interaction of kappa-agonists with a postsynaptic receptor is likely explanation for the inhibition of EPSPs. However, in some SG cells, the inhibition of EPSPs appears to be of presynaptic origin since dynorphin A1-17 and U-69,593 did depress the EPSPs in the absence of changes in passive membrane properties. Rp-cAMPS, a membrane permeant potent competitive inhibitor of cAMP-activated protein kinase, prevented the depressant effect of dynorphin A 1-17. This finding suggested a possibility that dynorphin A1-17, acting through a decrease in intracellular cyclic AMP levels, can reduce the synaptic responses of SG neurons. These results provide the first electrophysiological demonstration that the activation of kappa 1-opioid receptors inhibits AMPA receptor-mediated primary afferent neurotransmission in the substantia gelatinosa of the young rat spinal cord. This effect may mediate the ability of kappa-receptor agonists to produce antinociception.

Cerebellar and cerebral inputs to corticocortical and corticofugal neurons in areas 5 and 7 in the cat.

1. In the parietal cortex (Px, areas 5 and 7), the organization and characteristics of cerebellar and cerebral inputs and their effects on efferent neurons were investigated with the use of intracellular and extracellular recording techniques in the anesthetized cat. 2. Evoked field potential analysis revealed that two regions of the Px, the caudal bank of the ansate sulcus (Ans. S.) and the crown of the suprasylvian gyrus (Ssyl. G.), received converging input from the dentate and the interpositus nucleus. The cerebellar input to the caudal bank of the Ans. S. was relayed via the ventrolateral region of the ventroanterior-ventrolateral (VA-VL) complex of the thalamus, whereas the cerebellar input to the crown of the Ssyl. G. was relayed via the dorsomedial region of the VA-VL complex. 3. A total of 176 neurons was recorded intracellularly in the Px to examine inputs from the cerebellum. Of these, 72 neurons were corticocortical neurons projecting to the motor cortex (Mx), and 48 were corticofugal neurons to the pontine nucleus (PN). Intracellular staining with horseradish peroxidase revealed that the former corticocortical neurons were layer III pyramidal neurons and the latter corticofugal neurons were layer V pyramidal neurons. 4. Stimulation of the brachium conjunctivum (BC) produced di- or polysynaptic excitatory postsynaptic potentials (EPSPs) in corticocortical neurons projecting to the Mx and corticofugal neurons to the pontine nucleus in the Px. The characteristics of BC-evoked EPSPs were different between the bank of the Ans. S. and the crown of the Ssyl. G. In the bank of the Ans. S., the slope of the rising phase of the BC-evoked EPSPs was steeper, and their minimum latency was shorter by 0.8 ms than those in the crown of the Ssyl. G. These differences may reflect differences in the terminal distribution and conduction velocity of the thalamocortical fibers relaying cerebellar input to these two parietal areas. 5. Stimulation of the Mx produced mono- or disynaptic EPSPs in both corticocortical neurons projecting to the Mx and corticofugal neurons projecting to the pontine nucleus in the Px. For each neuron, effective sites for inducing EPSPs were distributed very widely and sometimes covered both areas 4 and 6. Extensive corticocortical projection from the Mx to the Px was confirmed by injection of an anterograde tracer into the Mx. 6. These data indicate that neurons in the Px receive inputs from both the cerebellum and the Mx and send outputs to the Mx and the cerebellum.(ABSTRACT TRUNCATED AT 400 WORDS)

Synaptic excitation of alpha-motoneurons by dorsal root afferents in the neonatal rat spinal cord.

1. Excitatory synaptic transmission in mono- and polysynaptic pathways between dorsal root afferents and alpha-motoneurons was studied in the spinal cord preparation of the neonatal rat isolated in vitro, using sharp-electrode intracellular recordings. 2. The duration of monosynaptic excitatory postsynaptic potentials (EPSPs) elicited in lumbar motoneurons were shortened after addition of the specific N-methyl-D-aspartate (NMDA) receptor blocker 2-amino-5-phosphonovaleric acid (APV) to the perfusate. The EPSPs were then completely blocked by the non-NMDA receptor blocker 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX). 3. A robust NMDA-receptor-mediated component of monosynaptic EPSPs was revealed by addition of CNQX to the bathing medium. This component reached as much as 30% of the EPSP amplitude, was evident at resting potential level in both low and normal Mg2+ Krebs saline, and could be completely abolished by addition of APV. These findings suggest that the NMDA-receptor-mediated component may contribute to monosynaptic excitation under normal conditions. 4. Polysynaptic EPSPs evoked in motoneurons in the fifth lumbar segment by stimulation of the fourth lumbar dorsal root in the presence of the glycine and gamma-aminobutyric acid A (GABAA) receptor blockers strychnine and bicuculline could be completely or partially blocked by application of either APV or CNQX. Suprathreshold activity could be then elicited in these motoneurons by increasing the stimulation intensity by a factor of 2 to 3. A complete blockade of polysynaptic excitation at these stimulation intensities was obtained only in the presence of both APV and CNQX. These results suggest that both receptor subtypes make a significant contribution to polysynaptic excitation of alpha-motoneurons by dorsal root afferents. 5. Analysis of variation in the amplitudes of the non-NMDA-receptor-mediated component of the monosynaptic EPSP and of the estimated (occurring 25 ms after the EPSP initiation) and the pharmacologically resolved NMDA component was done during low-frequency repetitive stimulation of the dorsal root. The kinetics of the initial decrease in EPSP amplitude during repetitive stimulation and the dependence of the EPSP amplitude on the stimulation frequency was similar for the NMDA- and non-NMDA-receptor-mediated components of the EPSPs. Addition of the GABAB receptor agonist L-(-) baclofen to the perfusate decreased the EPSP amplitude and reduced the frequency-dependent synaptic depression of both the NMDA- and non-NMDA-receptor-mediated components of monosynaptic EPSPs to the same level.(ABSTRACT TRUNCATED AT 400 WORDS)

N-methyl- d-aspartate stimulates the dephosphorylation of the microtubule-associated protein 2 and potentiates excitatory synaptic pathways in the rat hippocampus

We have studied the effect of brief (50–150 s) applications of N-methyl- d-aspartate (10–100 μM) on the phosphorylated state of the microtubule-associated protein 2 in slices of rat hippocampus. Following a similar experimental protocol we also studied the pattern of excitatory postsynaptic potentials intracellularly recorded in CA1 pyramidal cells elicited by stimulation of the Scharfer collateral-commissural pathway. N-Methyl- d-aspartate treatment produced a marked and specific dephosphorylation of the cytoskeletal microtubule-associated protein 2, which was not due to enhanced proteolytic activity. Dephosphorylation of the microtubule-associated protein 2 affects mainly the tubulin-binding domain of the molecule and seems to be a consequence of the activation of the Ca 2+/calmodulin-dependent phosphatase calcineurin, as it is partially inhibited by calmidazolium but not by okadaic acid. A few minutes after N-Methyl- d-aspartate treatment we observed a23 ± 17% increase in the amplitude of the monosynaptic excitatory postsynaptic potential recorded in the cells and the appearance of a large polysynaptic excitatory postsynaptic potential. Both effects lasted for several tens of minutes. The late polysynaptic potential was not observed when the CA3 and CA1 subfields were surgically separated. Our results indicate that the N-Methyl- d-aspartate receptor activation leads to the dephosphorylation of the microtubule-associated protein 2 via a Ca 2+/calmodulin phosphatase, probably calcineurine. This may, in turn, participate in the potentiation of synaptic efficacy.

Interactions between excitatory amino acids and tachykinins in the rat spinal dorsal horn

Whole-cell patch-clamp technique of freshly isolated rat spinal dorsal horn (DH) neurons, intracellular recording from DH neurons in a slice preparation, and high performance liquid chromatography with fluorimetric detection of release of endogenous glutamate and aspartate from spinal cord slice following activation of primary afferent fibers were employed to investigate interactions between excitatory amino acids (EAA) and tachykinins [substance P (SP) and neurokinin A (NKA)]. Potentiation of N-methyl-D-aspartate (NMDA)-, quisqualate (QA)- and α-amino 3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA)-, but not kainate-induced currents by SP and NKA was found. Spantide II, a claimed novel nonselective tachykinin antagonist, effectively blocked the SP (2 n M )-induced potentiation of the responses of DH neurons to NMDA. In the presence of glycine (0.1 μM), the SP-evoked increase of the NMDA-induced current was prevented. However, 7-chlorokynurenic acid (2 μM), a competitive antagonist at the glycine allosteric site of the NMDA receptor, led to the reestablishment of the SP effect. Brief high frequency electrical stimulation of primary afferent fibers produced a longlasting potentiation of presumed monosynaptic and polysynaptic excitatory postsynaptic potentials and sustained enhanced release of endogenous glutamate (218.3± 66.1 %) and aspartate (286.3 ± 58.0%). Possible functional implications of the observed phenomena are discussed in relation to transmission and integration of sensory information, including pain.

Origin of the in vivo rat piriform cortex activity recorded with voltage-sensitive dyes: comparison of the optical signals and the field potentials

The comparison of optocal recordings and evoked field potentials recorded on the rat piriform cortex pointed out that both signals were strongly correlated. As the field potentials, the two waves of the optical signals originated from the mono- (direct olfactory bulb afferents) and polysynaptic (intrinsic association fibers) excitatory postsynaptic potentials. Such optical recordings will be used for studying spatiotemporal distribution of the piriform cortex activity.

Excitatory amino acid receptors involved in primary afferent-evoked polysynaptic EPSPs of substantia gelatinosa neurons in the adult rat spinal cord slice.

Intracellular recordings were made from substantia gelatinosa (SG) neurons in spinal cord slices to determine a subclass of excitatory amino acid receptors involved in polysynaptic excitatory postsynaptic potentials (EPSPs). In the majority of neurons, polysynaptic EPSPs evoked by A delta fiber were not affected by 2-amino-5-phosphonovaleric acid (APV), while all EPSPs including monosynaptic EPSPs were depressed by 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX). All spontaneous EPSPs were blocked by CNQX, while spontaneous EPSPs in a few SG neurons were attenuated by APV. These observations suggest that polysynaptic EPSPs evoked through A delta fibers are predominantly mediated by activation of the non-N-methyl-D-aspartate (non-NMDA) receptor subclass.

Afferent projections in the spinal accessory nerve to the facial motoneurons of the cat

Stimulation of the accessory nerve evoked polysynaptic excitatory postsynaptic potentials (EPSPs) in the facial nucleus (FN) neurons of anesthetized cats. From the experiments with severance of C 1–C 3 dorsal roots, it is suggested that accessory afferents enter the braistem through the accessory nerve. It was also found that stimulation of the solitary tract nucleus produced exclusively monosynaptic EPSPs in the FN neurons and the afferent volleys are most likely to be relayed at the solitary tract nucleus.

Correlates of Habituation of a Polysynaptic Reflex in Crayfish In Vivo and In Vitro.

Reflex leg levation habituates during repeated electrical stimulation of mechanosensory afferents in the dactyl of the fifth walking leg of the crayfish, Procambarus clarkii. This was investigated in decerebrate crayfish, and reproduced in an isolated thoracic ganglion preparation. In vivo, trains of stimuli delivered every 2.5 s produced a gradual decrease in the amplitude of the mechanical response, and a concomitant decrease in the number of impulses per burst in the levator muscle myogram. Near complete recovery occurred after 10 min rest, and transient dishabituation was observed after electrical stimulation of the telson. Less frequent or stronger stimuli led to less rapid habituation. In vitro, the same parametric characteristics of habituation were observed in the levator nerve responses, while the intrinsic variability of the reflex was reduced. The response decrement was shown to be unrelated to changes in the afferent excitation. Evoked polysynaptic excitatory postsynaptic potentials (EPSPs) in levator motorneurons decreased in parallel with the levator neurogram. This decrease was unrelated to any change in the resting membrane potential of the levator motorneurons. Interneurons with habituating EPSPs, antagonistic depressor motorneurons with habituating inhibitory postsynaptic potentials and non-habituating responses in other motorneuronal groups were also found. These findings point to a central locus of habituation upstream from the motorneurons, and offer prospects for a detailed investigation of the mechanisms of habituation in a polysynaptic system.

Neuronal mechanisms of interaction of Deiters nucleus with the cerebral cortex.

The effects of stimulation of the vestibular nerve and five different cerebral cortex areas on the neuronal activity of the lateral vestibular nucleus of Deiters were studied. Stimulation of the cerebral cortex is shown to lead to antidromic and synaptic activation of Deiters neurons. The synaptic potentials of Deiters neurons evoked from the cerebral cortex were of mono- and polysynaptic origin. In particular, stimulation of the cerebral cortex evoked in Deiters neurons mono- and polysynaptic excitatory postsynaptic potentials. Collaterals of vestibulospinal neurons reaching different cortex fields as well as convergence of influences from these cortex fields on Deiters neurons were revealed. Inhibitory effects of the cerebral cortex on Deiters neurons were of polysynaptic origin and occurred rarely. The topical correlation between Deiters nucleus and different areas of the cerebral cortex was found. The peculiarities and functional significance of the effects obtained are discussed.

Primary afferents evoke excitatory amino acid receptor-mediated EPSPs that are modulated by presynaptic GABAB receptors in lamprey

1. The primary afferent neurons (dorsal cells) are of two types in lamprey, which are fast (touch) and slowly adapting (pressure), respectively. Intracellular stimulation of such sensory neurons evokes mono- and polysynaptic excitatory postsynaptic potentials (EPSPs) in spinobulbar neurons (giant interneurons) and in unidentified interneurons. Paired intracellular recordings between identified sensory cells and spinobulbar neurons made it possible to study the synaptic transmission in detail. It is shown that both touch and pressure primary afferents utilize excitatory amino acid (EAA) transmission and, furthermore, that these effects are subject to a presynaptic GABAB receptor modulation. 2. The monosynaptic mixed electrical and chemical EPSPs in giant interneurons had a mean peak amplitude of 3.2 +/- 1.3 (SD) mV, a time to peak of 4.7 +/- 1.2 ms, and a duration at one-half peak amplitude of 9.4 +/- 3.2 ms. Corresponding results were obtained with dorsal root or dorsal column stimulation. Seventy percent of the fast-adapting dorsal cells of the "touch" type evoked monosynaptic mixed EPSPs in giant interneurons, whereas only 3% of the slowly adapting "pressure" dorsal cells did. 3. The chemical part of the monosynaptic EPSPs evoked in giant interneurons was, in all cases tested, blocked by application of EAA antagonists, like the nonselective antagonist kynurenic acid (KYAC; 2 mM). The selective kainate/alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor antagonist 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX; 5 microM) had a similar effect, whereas the selective N-methyl-D-aspartate (NMDA) receptor antagonist 2-aminophosphono-5-valeric acid (AP-5; 200-400 microM) did not change the EPSP, even in the absence of magnesium ions. 4. The monosynaptic excitatory synaptic transmission was modulated by application of the selective GABAB receptor agonist L-baclofen (5-10 mM local droplet application or 100-1,000 microM bath applied) or by gamma-aminobutyric acid (GABA; 100-1,000 microM), also when GABAA receptor-evoked effects were blocked by bicuculline (10 microM). L-baclofen or GABA in combination with bicuculline did not evoke any effects in the postsynaptic neuron on membrane potential, input resistance, or spike threshold. Therefore the effects of the GABAB receptor activation most likely occurs at the presynaptic afferent level. 5. In conclusion, the monosynaptic excitation from skin mechanoreceptors evoked in spinobulbar neurons is mediated by EAA receptors of the kainate/AMPA type. GABAB receptor activation causes a depression of this EPSP, most likely because of a presynaptic action. GABA interneurons are known to form close appositions on sensory axons in the lamprey.

Synaptic organization of tectal-facial pathways in cat. II. Synaptic potentials following midbrain tegmentum stimulation

1. The organization of the synaptic pathways underlying midbrain tegmentum influence over the facial musculature was studied with the use of an acute electrophysiological approach in the cat. Under pentobarbital sodium anesthesia, synaptic potentials were recorded intracellularly in antidromically identified facial motoneurons following electrical stimulation of the paralemniscal zone. The cells of origin and the pathways responsible for the potentials evoked from the paralemniscal zone were defined with the use of retrograde transport of horseradish peroxidase (HRP). The putative role of the paralemniscal zone with regard to the production of disynaptic, tectally evoked potentials in facial motoneurons was investigated both by inactivating this nucleus with injections of lidocaine and by making acute brain stem lesions to sever the paralemniscal-facial and other afferent pathways. 2. Following paralemniscal stimulation, monosynaptic, excitatory postsynaptic potentials (EPSPs) with latencies ranging from 0.6 to 0.9 ms, steep rising phases, and amplitudes in excess of 4.0 mV were recorded in motoneurons of the temporal and auriculoposterior subdivisions, which supply the pinna muscles. Smaller amplitude EPSPs (less than 1.0 mV) with monosynaptic latencies were observed in the zygomatic subdivision. Polysynaptic EPSPs with latencies ranging from 1.0 to 1.8 ms were also observed in all three of these subdivisions. However, only long-latency EPSPs, arriving at 2.0 ms or later, were present in ventral subdivision motoneurons. 3. Inhibitory postsynaptic potentials (IPSPs) were also frequently recorded in facial motoneurons after paralemniscal stimulation. Monosynaptic IPSPs with latencies ranging from 0.8 to 1.2 ms and amplitudes in excess of 4.0 mV were recorded in facial motoneurons of the temporozygomatic and auriculoposterior subdivisions, as were polysynaptic IPSPs with latencies ranging from 1.2 to 1.8 ms. IPSPs were sometimes observed in combination with a smaller, shorter latency EPSPs. Only long-latency IPSPs of greater than 2.0 ms were recorded in ventral subdivision motoneurons. In all cases, both the EPSPs and the IPSPs were graded in character and could be augmented by multiple stimuli. 4. The contralateral paralemniscal zone and the supraoculomotor area, bilaterally, represented the two most prominent afferent sources labeled after HRP injection of the facial nucleus. The superior colliculus and numerous reticular formation regions were also identified as facial nucleus afferents by the presence of retrogradely labeled cells. The retrogradely labeled cells in the paralemniscal zone exhibited heterogeneous soma size. HRP-labeled axons of the paralemniscal-facial pathway were observed to cross the midline by traveling ventral to the brachium conjunctivum in the caudal mesencephalon.(ABSTRACT TRUNCATED AT 400 WORDS)

Actions of excitatory amino acid antagonists on synaptic potentials of layer II/III neurons of the cat's visual cortex.

Actions of excitatory amino acid (EAA) antagonists on the responses of cells in layers II/III and IV of the cat's visual cortex to stimulation of layer VI and the underlying white matter were studied in slice preparations. Antagonists used were 2-amino-5-phosphonovalerate (APV), a selective antagonist for the N-methyl-D-aspartate (NMDA) type of EAA receptors, and kynurenate, a broad-spectrum antagonist for the three types of EAA receptors. In extracellular recordings it was demonstrated that most of the layer II/III cells were sensitive to APV, while the great majority of the layer IV cells were not. By contrast, kynurenate suppressed the responses completely in both layers. Excitatory post-synaptic potentials (EPSPs) evoked by stimulation of layer VI and the while matter were recorded intracellularly from layer II/III neurons. To determine whether the EPSPs were elicited mono- or polysynaptically, the synaptic delay for each EPSP was calculated from a pair of onset latencies of EPSPs evoked by stimulation of the two sites. Forty-two percent of the layer II/III cells were classified as having monosynaptic EPSPs. In 60% of these monosynaptic cells, the rising slope of the EPSPs was reduced by APV while in the other 40%, it was not. In the former (APV-sensitive cells), subtraction of the APV-sensitive component from the total EPSP indicated that the onset latency of the NMDA receptor-mediated component was roughly equal to that of the non-NMDA component. In the latter (APV-resistant cells), only the slowly-decaying component was in part mediated by NMDA receptors. The conduction velocities of the afferent fibers innervating APV-resistant cells were slower than those of the APV-sensitive cells, suggesting that both types of cells are innervated by different types of afferents. The polysynaptic EPSPs of almost all layer II/III cells were sensitive to APV. The subtraction method indicated that the NMDA component had about the same magnitude as the non-NMDA components. When the slices were superfused by a Mg2+-free solution, the EPSPs were potentiated dramatically, but this potentiation was reduced to the control level during the administration of APV. Similarly, APV-sensitive components were potentiated during the administration of bicuculline, a selective antagonist for gamma-aminobutyric acid receptors of A type. These results suggest that NMDA receptors participate, at varying degrees, in excitatory synaptic transmission at most layer II/III cells in the cat's visual cortex, and their actions appear to be regulated by intracortical inhibition.

Long-term potentiation in frontal cortex: Role of NMDA-modulated polysynaptic excitatory pathways

The present study examined the role of N- methyl- d-aspartic acid (NMDA) receptors in synaptic plasticity in regular-spiking cells of rat frontal cortex. Intracortical stimulation, at levels subthreshold for elicitation of action potentials, evoked a late excitatory postsynaptic potential (EPSP) in layer II III neurons that was sensitive to the selective NMDA antagonist d-2-amino-5-phosphonovaleric acid (APV). This late EPSP showed marked short-term frequency-dependent depression, suggesting that it is polysynaptic in origin. Polysynaptic late EPSPs were selectively enhanced following high-frequency stimulation. This sustained increase in synaptic efficacy, or long-term potentiation, was expressed in regular spiking cells and appeared to result from activation of NMDA receptors on excitatory interneurons. These data demonstrate the existence of an NMDA-modulated polysynaptic circuit in the neocortex which displays several types of use-dependent plasticity.

Voltage-clamp analysis of taurine-induced suppression of excitatory postsynaptic potentials in frog spinal motoneurons.

1. The depressant actions of taurine applications on lumbar motoneurons in the isolated frog spinal cord were studied using conventional intracellular recordings and the two-electrode voltage-clamp technique. 2. With microelectrodes containing K+-acetate, 0.75-2 mM taurine mostly induced a hyperpolarization that often faded or turned into depolarization during the continuous application. A higher concentration (5-7.5 mM) depolarized a majority of cells. The effects on the membrane potential were associated with an increase in input conductance (approximately 285%). 3. The reversal potential of the taurine-induced currents was approximately -70 mV, with microelectrodes containing K+-acetate. In recordings using KCl-filled electrodes, taurine (less than or equal to 2 mM) produced a large depolarization (greater than or equal to 20 mV) at resting potentials near -50 mV, thereby indicating that the reversal potential was positively shifted by loading the cell with Cl-. These results suggest that the taurine potentials were mediated predominantly by an increased Cl- permeability. 4. Voltage-dependent relaxations of taurine currents were observed in 10 of 14 neurons. 5. A linear relation was found between the input conductance and the amount of current required to generate a 1-mV increment in EPSP at resting potential. 6. Polysynaptic excitatory postsynaptic potentials (EPSPs) and currents (EPSCs) were more susceptible to taurine than the monosynaptic responses. Taurine (less than 1 mM) seemed to suppress the interneurons mediating polysynaptic pathways. 7. Monosynaptic EPSPs and EPSCs were decreased with higher concentrations of taurine (greater than 1 mM). The percent reduction of EPSPs and that of the corresponding EPSCs had a positive correlation (r = 0.95), whereas, there was no significant correlation between changes in EPSPs and in input conductance, and between changes in EPSCs and in input conductance. The amount of current required to produce a 1-mV increment of EPSP was increased in the presence of taurine, in association with the increased input conductance. 8. Taurine suppressed synaptic potentiation of EPSPs evoked by paired stimuli, at an interval of 60-180 ms. Gamma-D-glutamylglycine, an antagonist of receptors for excitatory amino acids, greatly reduced the amplitude of EPSPs, but had little effect on synaptic potentiation. 9. Taurine suppressed glutamate currents evoked at membrane potentials, clamped near rest in low Ca2+, high Mg2+ solution. 10. These findings suggest that the taurine-induced reduction of EPSPs is due mainly to suppression of EPSCs, through both presynaptic and postsynaptic mechanisms.(ABSTRACT TRUNCATED AT 400 WORDS)

Selforganization and information processing of neural networks

To investigate whether corticothalamic (CT) neurons in the motor cortex (Mx) receive cerebellar input via the ventroanterior–ventrolateral nucleus of the thalamus (VA–VL), we recorded intracellular potentials from neurons in the Mx of anesthetized cats and examined effects of stimulation of the VA–VL and the brachium conjunctivum on them. After this electrophysiological identification, horseradish peroxide (HRP) was injected iontophoretically into the recorded neurons for morphological analysis. We identified 34 neurons as CT neurons by their antidromic response to stimulation of the VA–VL, of which 13 were layer VI CT neurons and 21 were layer V CT neurons. A majority of the CT neurons of both layers VI and V received monosynaptic excitatory postsynaptic potentials (EPSPs) from the VA–VL and di- or polysynaptic EPSPs from the cerebellum. The laminar distribution and morphological characteristics of single CT neurons receiving cerebellar input were analyzed on 19 HRP-labeled CT neurons. Eight layer V and six layer VI CT neurons were reconstructed from serial sections. All the reconstructed layer VI CT neurons were modified pyramidal neurons whose apical dendrites ended in layer III or V, and all the stained layer V CT neurons were typical pyramidal neurons, although the laminar and tangential distribution of recurrent collaterals of these neurons varied from neuron to neuron.