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Transient protein kinase C activation primes long-term depression and suppresses long-term potentiation of synaptic transmission in hippocampus.

Activity-dependent long-lasting plasticity in hippocampus and neocortex includes long-term potentiation (LTP) and long-term depression (LTD) of synaptic strength. Recent studies have confirmed theoretical predictions that the sensitivity of LTP- and LTD-inducing mechanisms is dynamically regulated by previous synaptic history. In particular, prior induction of either repeated short-term potentiations or LTP lowers the threshold for induction of LTD and raises the threshold for LTP. In the current study, transient activation of protein kinase C with phorbol 12,13-diacetate was able to substitute for synaptic activity in priming synapses to exhibit enhanced homosynaptic LTD and to suppress the induction of LTP at Schaffer collateral synapses in area CA1 of hippocampal slices. This priming lasted 30 min, but not 3 hr, following phorbol 12,13-diacetate bath application. These data suggest that a protein kinase C-sensitive phosphorylation site may be an activity-sensitive target mediating the rapid expression of LTP and LTD.

Animals↗

The origin of rhythmic fast subthreshold depolarizations in thalamic relay cells of rats under urethane anaesthesia.

Intracellular recordings were performed in relay neurons of the dorsal thalamus in rats under urethane anaesthesia. In 77 out of 127 neurons of the ventro-posterolateral and ventral lateral nuclei, but not in neurons of the ventro-posteromedial and posterior nuclei, a highly rhythmic pattern of subthreshold depolarizations was present at rest. The average frequency of these rhythmic depolarizations in ventro-posterolateral cells was 23.36 +/- 11.48 Hz (range: 6-60 Hz); in ventral lateral relay cells higher frequencies were observed (65.86 +/- 17.42 Hz; range: 17-95 Hz). The rhythmic subthreshold events were identified as excitatory postsynaptic potentials generated by the regular firing of prethalamic afferents located in dorsal column and deep cerebellar nuclei. Indeed, in cells of the ventro-posterolateral nucleus these spontaneous potentials had a waveform similar to that of synaptic potentials triggered by somatosensory stimulation. They increased in amplitude with membrane hyperpolarization and their rhythmic occurrence was not affected by the injection of large inward currents. Moreover, they persisted after capsular transection, but they could no more be recorded in ventro-posterolateral cells after lesion of dorsal column nuclei. Finally, it was found that prethalamic afferents within the deep cerebellar nuclei discharged spontaneously in a rhythmic manner within the same frequency band as that of the rhythmic synaptic potentials recorded in ventral lateral cells. On the basis of these results, it is concluded that the rhythmic subthreshold depolarizations observed in thalamic neurons of animals under urethane anaesthesia are not generated intrinsically but that they represent excitatory postsynaptic potentials of prethalamic origin.(ABSTRACT TRUNCATED AT 250 WORDS)

Anesthesia↗

Experimental evaluation of input-output models of motoneuron discharge.

1. We measured the modulation of the background firing rate of cat spinal motoneurons produced by simulated, repetitive excitatory postsynaptic potentials (EPSPs) to test the accuracy of several proposed motoneuron input-output functions. Rhythmic discharge was elicited in the motoneurons by injecting suprathreshold current steps 1-1.5 s in duration. On alternate trials, trains of short (0.5-5 ms) current pulses were superimposed on the current steps to stimulate the effects of trains of individual EPSPs. The increase in firing rate (delta F) due to the addition of the pulses was calculated as the difference in motoneuron discharge rate between trials with and without the superimposed pulse trains. 2. In the same motoneurons, we were able to study the effects of changes in pulse frequency, duration, and amplitude, as well as changes in the background discharge rate. A sublinear relationship between pulse rate and delta F was observed, with delta F rising relatively steeply with increasing pulse frequency at low pulse rates and saturating at high pulse rates. A similarly shaped relation was observed between delta F and pulse duration. In contrast, delta F generally increased in a greater than linear fashion with increasing pulse amplitude. 3. In previous studies we demonstrated that when a relatively constant synaptic input is produced by high-frequency synaptic activity, delta F is approximately equal to the product of the net synaptic current reaching the soma and the slope of the motoneuron's steady-state frequency-current (f-I) relation. In the present study, this input-output function consistently underestimated the observed delta F, particularly for low input rates, indicating that the transient current pulses are more effective in modulating motoneuron discharge than an equivalent amount of constant current. 4. Other investigators have proposed input-output functions derived from the relation between synaptic potential amplitude and the magnitude of the peak of a cross correlogram compiled from the discharge of the pre- and postsynaptic neurons. These functions consistently overestimated the observed delta F, particularly for high pulse rates. This overestimation may result in part from the fact that the effects of a synaptic potential (or current pulse) on postsynaptic discharge probability also include a period of decreased firing probability. Moreover, the cross correlation function may depend on the arrival rate of synaptic potentials (or current pulses). 5. Another proposed input-output function based on a simple threshold-crossing model of the motoneuron with a fixed spike threshold predicts firing rates that were often close to the observed delta F. However, the model did not reproduce the observed relations between delta F and input pulse rate or pulse duration. 6. The deficiencies of the basic threshold-crossing model may arise from the fact that it does not incorporate variations in membrane conductance and firing threshold that occur in real motoneurons. A more complete motoneuron model that incorporates both of these features was able to replicate the observed delta Fs associated with changes in input pulse frequency and duration.

Animals↗

Potentiation of synaptic reflexes by D-serine in the rat spinal cord in vitro.

6-Cyano-7-nitroquinoxaline-2,3-dione (CNQX) (10 microM) depressed dorsal root-evoked ventral and dorsal root potentials of the in vitro immature rat spinal cord to 26.3 +/- 5.2 S.E.M. and 40.8 +/- 2.7% of control values respectively. These depressant effects of CNQX were partially reversed by D-serine (EC50 values 39.7 microM +/- 8.7 S.E.M. N = 6 and 34.9 +/- 12.5 microM, N = 5 for ventral root potential and dorsal root potential respectively). Under our experimental conditions, which included the presence of Mg2+ (0.75 mM) in the bathing medium, no measurable potentiation of these synaptic reflexes by D-serine was recorded in the absence of CNQX. These data indicate that CNQX, in addition to its depressant effect at non-NMDA receptors, depresses an NMDA receptor-mediated component of segmental transmission through its action at the glycine site of the NMDA receptor complex.

6-Cyano-7-nitroquinoxaline-2,3-dione↗

Morphology and electrophysiology of guinea-pig paratracheal neurones.

BACKGROUND: Although guinea-pig tracheal preparations are used as models of asthma, the morphological and electrophysiological characteristics of its associated ganglion neurones (paratracheal neurones) have not been characterized. METHODS: Intracellular staining and electrophysiological recording techniques have been applied to guinea-pig paratracheal neurones in isolated preparations. RESULTS: Most (32/35) neurones were multipolar, with many short (< 70 microns), finely tapering processes and one or more long processes; the latter, which were traced for up to 400 microns, travelled along the interconnecting nerve trunks, often in pairs, or over smooth muscle bundles. About 20% (6/32) of neurones had conspicuous somal extensions that gave rise to 3-8 processes. The soma morphology of neurones of the intrinsic ganglionated plexus close to the trachealis muscle were usually more complex than those in or associated with recurrent or vagal nerve trunks. Two types of neurone were identified electrophysiologically; neurones with fast excitatory synaptic potentials were found only in ganglia located very close to the smooth muscle, whereas > 90% of neurones lacking synaptic inputs were associated with recurrent nerve trunks. Transmural or focal electrical stimulation failed to evoke either slow inhibitory or slow excitatory (cholinergic or non-cholinergic) synaptic potentials in either electrophysiological type. CONCLUSIONS: It is tentatively concluded that the neurones of the intrinsic ganglionated plexus receiving synaptic input probably provided the para-sympathetic innervation to effector cells (such as trachealis muscle). Both these and the spiking neurones located in or near nerve trunks showed little potential for synaptic modulation of their excitability.

Animals↗

Development of the embryonic neuromuscular synapse of Drosophila melanogaster.

We have examined the embryonic development of an identified neuromuscular junction (NMJ) of Drosophila melanogaster using whole-cell patch-clamp and a variety of physiological and morphological techniques. Synaptic current at the embryonic NMJ is carried through a large-conductance (200 pS) L-glutamate receptor. Early synaptic communication is characterized by frequent, brief (< 10 msec) currents carried through few (1-10) receptors and relatively rare, prolonged currents (up to seconds) of similar amplitude. The brief currents have a time course similar to the mature larval excitatory junction currents (EJCs), but the prolonged currents are restricted to early stages of synaptogenesis. The amplitude of EJCs rapidly increases, and the frequency of the prolonged currents decreases, after the initial stages of synaptogenesis. Early prolonged (seconds), nonspiking synaptic potentials are replaced with rapid (< 0.10 sec), spiking synaptic potentials later in development. The early synapse appears tenuous, easily fatiguable, and with inconsistent communication properties. Synaptogenesis can be divided into a sequence of progressive stages. (1) Motor axon filopodia begin neurotransmitter expression and concurrent exploration of the myotube surface. (2) Myotubes uncouple to form single-cell units soon after motor axon contact. (3) A small number of transmitter receptors are homogeneously displayed on the myotube surface immediately following myotube uncoupling. (4) Endogenous transmitter release from pioneering growth cones is detected; nerve stimulation elicits postsynaptic EJC response. (5) Motor axon filopodia and transmitter receptors are localized to the mature synaptic zone; filopodial localization is complete in advance of receptor localization. (6) A functional neuromuscular synapse is formed; endogenous muscular activity begins; nerve stimulation leads to muscle contraction. (7) Morphological presynaptic specializations develop; synapse develops mature morphology. (8) A second motor axon synapses on the myotube at the pre-established synaptic zone. (9) Vigorous neuromuscular activity, characteristic of larval locomotory movements, begins. (10) A second stage of receptor expression begins and continues through the end of embryogenesis. In general, Drosophila neuromuscular synaptogenesis appears similar to neuromuscular synaptogenesis in known vertebrate preparations. We suggest that this system provides a model for synaptogenesis in which investigation can be readily extended to a genetic and molecular level.

Animals↗

Sources of excitatory synaptic inputs to neurochemically identified submucous neurons of guinea-pig small intestine.

The locations of the cell bodies of axons responsible for synaptic potentials evoked in neurochemically identified submucous neurons of the guinea-pig small intestine were investigated using a combination of intracellular recording, immunohistochemical and lesioning techniques. The myenteric plexus was removed from an 8-15 mm wide ring of small intestine in 15 anaesthetized guinea-pigs. After the operations, the animals were allowed to recover for 3-7 days so that nerve terminals that were disconnected from their cell bodies would degenerate. Preparations of submucous plexus were then made from the region under the lesion. Submucous neurons were impaled with electrodes containing a mixture of KCl and the fluorescent dye, Lucifer yellow CH, and their electrophysiological properties determined. They were then filled with the dye for subsequent reidentification after processing for immunohistochemical localization of vasoactive intestinal peptide (VIP) and neuropeptide Y (NPY). The synaptic inputs to 33 neurons were characterized: 19 of these were found to be VIP-reactive, 7 were NPY-reactive and 7 were negative for both VIP and NPY. These results were compared to those obtained from 43 neurons in control preparations: 25 VIP-reactive, 9 NPY-reactive and 9 negative for both VIP and NPY. Removal of the myenteric plexus caused a significant reduction in the number of inputs providing fast excitatory synaptic potentials to each of the neurochemically defined classes of neurons. The lesions also caused a significant reduction in the number of VIP-reactive neurons that exhibited slow excitatory synaptic potentials (other neurochemical types do not normally exhibit such responses).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Papain effects on rat hippocampal neurons in the slice preparation.

Intracellular recordings were made from the CA1 stratum pyramidale region of rat hippocampal slices. Papain was applied to the cells via bath perfusion, and its effects on membrane properties, synaptic potentials and responses to pressure application of gamma-aminobutyric acid (GABA) were assessed. Papain did not markedly affect neuronal input resistance, resting potential or action potentials with treatment times lasting over one hour. Synaptic potentials were initially enhanced and then gradually abolished, with the fast inhibitory postsynaptic potential being the most sensitive and the late, potassium-dependent hyperpolarization being the most resistant to enzyme. Responses to GABA were enhanced by papain, the GABA-activated conductance increased, and a slow depolarizing wave appeared which resembled the effect caused by pentobarbital on these neurons. This study indicates that the use of papain in the acutely dissociated neuron preparation is not responsible for the dramatic increase in resting input resistance seen in these neurons. The GABA-activated conductance may be affected by the enzyme.

Action Potentials↗

Functional organization in the terminal segments of the spinal cord with a consideration of central excitatory and inhibitory latencies in monosynaptic reflex systems.

Prominent monosynaptic and disynaptic reflex discharges characterize ipsilateral reflex transmission in the third sacral segment. Convergence upon the motoneurons from the two sides of the body is inhibitory, that through disynaptic paths excitatory. The relative latencies of excitation and inhibition of reflex responses, of excitatory and inhibitory synaptic potentials, and of various aspects of impulse discharge in motoneurons are considered. It is concluded: (1) that a direct (i.e. monosynaptic) action of primary afferent collaterals upon motoneurons is responsible for inhibition of monosynaptic reflex discharge of antagonist motoneurons within a myotatic unit; (2) that the inhibitory postsynaptic potential as described is not the primary agency for monosynaptic reflex inhibition of monosynaptic reflex discharge; (3) that, however, a common causal agent may be responsible for inhibition of reflex discharge and for generation of an inhibitory postsynaptic potential; and (4) that the inhibitory post-synaptic potential may be linked with, or be the agent for, inhibition of soma response.

Motor Neurons↗

Synaptic actions of peripheral nerve impulses upon Deiters neurones via the climbing fibre afferents.

1. The cerebellar integration of sensory inputs to Deiters neurones was studied in cats under Nembutal anaesthesia.2. Stimulation of peripheral nerves produced in the Deiters neurones a sequence of an initial excitatory post-synaptic potential (e.p.s.p.) and a later inhibitory post-synaptic potential (i.p.s.p.), or a relatively small e.p.s.p.3. The Deiters neurones were classified as forelimb (FL)- or hind limb (HL)-type cells according to the location of the most effective peripheral nerve. In the FL cells stimulation of the forelimb nerves produced the e.p.s.p.-i.p.s.p. sequence (dominant response), while stimulation of the hind limb nerves was ineffective or produced the small e.p.s.p. (non-dominant response). In contrast, in the HL cells the non-dominant response was evoked from the forelimb nerves, and the dominant response from the hind limb nerves.4. The stimulus intensity-response relation indicates that Group I and II muscle afferents and low and high threshold cutaneous afferents contribute to the dominant and non-dominant responses.5. Antidromic identification of these Deiters neurones revealed that 90% of the HL cells and 85% of the FL cells project to the lumbo-sacral and cervico-thoracic segments of the spinal cord, respectively, while 10% of the HL cells and 15% of the FL cells innervate the cervico-thoracic and lumbo-sacral segments, respectively.6. The mean latency of the e.p.s.p. evoked from the forelimb nerves was 14 msec in the FL cells and 13 msec in the HL cells, and the latency of the e.p.s.p. evoked from the hind limb nerves was 17 msec in the FL cells and 18 msec in the HL cells. The later i.p.s.p. regularly followed the onset of the e.p.s.p. with a delay of 3-5 msec.7. The dominant and non-dominant responses in both types of cells exhibited the following three characteristic features: (i) a strong depression after conditioning stimulation of the inferior olive, (ii) an increase of the inferior olivary excitability during the responses, and (iii) a striking frequency depression with stimulation at relatively low frequency (5-10/sec).8. Consequently it was concluded that all of the responses were produced through the climbing fibres originating from the inferior olive, the i.p.s.p.s due to inhibition from Purkyne cells activated by the climbing fibres and the e.p.s.p.s due to excitation from the collaterals of the climbing fibres.

Animals↗

Neuronal responses to lemniscal stimulation in laminar brain slices of the inferior colliculus.

The central nucleus of the inferior colliculus (ICC) receives inputs from all parts of the auditory brainstem and transmits the information to the forebrain. Fibrodendritic laminae of the ICC provide a structural basis for a tonotopic organization, and the interaction of inputs within a single layer is important for ICC processing. Transverse slice planes of the ICC sever the layers and many of the ascending axons that enter through the lateral lemniscus. Consequently, the activity initiated within a lamina by a pure lemniscal stimulus is not well characterized. Here, we use a slice plane that maintains the integrity of the laminae in ICC and allows the axons in the lateral lemniscus to be stimulated at a distance from the ICC. We examined both the postsynaptic currents and potentials of the same neurons to lemniscal stimuli in this laminar brain slice. Our main finding is that lemniscal stimulation evokes prolonged synaptic potentials in ICC neurons. Synaptic potential amplitudes and durations increase with lemniscal shock strength. In approximately 50% of ICC neurons, the postsynaptic potential is equal in duration to the postsynaptic current, whereas in the remaining neurons it is three to four times longer. Synaptic responses to single shocks or shock trains exhibit plateau potentials that enable sustained firing in ICC neurons. Plateau potentials are evoked by N-methyl-D-aspartate (NMDA) receptor activation, and their amplitudes and durations are regulated by both NMDA-R and gamma-aminobutyric acid A (GABAA)-R activation. These data suggest that in the intact laminae of the ICC, lemniscal inputs initiate sustained firing through monosynaptic and polysynaptic NMDA-mediated synapses regulated by GABAA synapses.

Animals↗

Clozapine-induced potentiation of synaptic responses in the perforant path-dentate gyrus pathway in chronically prepared rabbits.

To examine the contribution of N-methyl-D-aspartate (NMDA) receptors in the mechanisms underlying the action of antipsychotics, we investigated the effects of a representative atypical antipsychotic, clozapine (CLZ), on the induction of long-term potentiation (LTP) in the perforant path-dentate gyrus pathway in 15 chronically prepared rabbits. Eventually, neither low (10 mg/kg) nor high (20 mg/kg) doses of CLZ intraperitoneally injected had any effects on LTP induction. However, the high dose CLZ always potentiated the ordinary synaptic responses induced by single stimulations before the LTP induction. The present study indicates a new finding, the presence of "CLZ-induced potentiation', although it needs further investigation whether NMDA receptors contribute to this potentiation.

Animals↗

Adenosine 3',5'-monophosphate: electrophysiological evidence for a role in synaptic transmission.

Synaptic potentials and changes in resting membrane potentials of superior cervical ganglia of the rabbit were measured in the presence of adenosine 3',5'-monophosphate and agents that affect its metabolism. Adenosine 3',5'-monophosphate and its mono- and dibutyryl derivatives caused a hyperpolarization of the postganglionic neurons. Theophylline potentiated the slow inhibitory postsynaptic potential that follows synaptic transmission, as well as the hyperpolarization of postganglionic neurons caused by exogenous dopamine. Conversely, prostaglandin E(1) inhibited both the slow inhibitory postsynaptic potential and the dopamine-induced hyperpolarization. We hypothesize that the slow inhibitory postsynaptic potential as well as the dopamine-induced hyperpolarization result from increased amounts of adenosine 3'5'-monophosphate in the postganglionic neurons. The dibutyryl derivative of guanosine 3'5'-monophosphate caused a depolarization of the postganglionic neurons, which is consistent with the possibility that guanosine 3'5'-monophosphate mediates synaptic transmission at muscarinic cholinergic synapses.

Animals↗

A statistical method for correcting distortions of amplitude distribution histograms due to collisions of synaptic events.

The waveform of spontaneous synaptic potentials or currents comprising synaptic noise can be significantly distorted when these events are closely spaced due to a high frequency activity in the presynaptic inputs that generate them. It is essential to correct these alterations prior to measurements of overlapping miniature and/or postsynaptic potentials, in order to provide reliable information about their true amplitude distributions, and to avoid spurious peaks in the resulting histograms. In this paper we describe a statistical method for making these corrections, its range of application, and its theoretical background. Its use becomes necessary when the frequency of events is of the order of 8-50 Hz, depending upon their time to peak, which ranges from 6 to 1 ms in most synaptic potentials recorded in the central nervous system.

Action Potentials↗

Distribution of climbing fibres on cerebellar Purkinje cells in X-irradiated rats. An electrophysiological study.

1. The distribution of climbing fibres on cerebellar Purkinje cells has been studied with intracellular recordings in X-irradiated and normal rats. 2. In the treated rats, multiple steps in the post-synaptic potential were elicited in 57% of the Purkinje cells by graded stimulation of the climbing fibres, the response was all-or-none in character in the other cells and in all Purkinje cells recorded in normal animals. In the neurones exhibiting the former type of response, no collision was seen along the afferent fibres during interaction experiments between just-threshold juxtafastigial and maximal olivary stimulations, whereas a collision always occurred when all-or-none responses were recorded. 3. These results show that in X-irradiated rats, the majority of Purkinje cells have a multiple innervation by two to four climbing fibres, instead of the one-to-one relationship seen normally. 4. Input resistances and total electrotonic lengths of Purkinje cells were measured in normal and treated rats. Mean values for these two parameters were higher than normal in multiply innervated cells. 5. Mean time course and mean current for reversal of the post-synaptic potential elicited in Purkinje cells by stimulation of the climbing fibres were nearly the same in mono- and in multiply innervated neurones. In multiply innervated cells, time courses and currents for reversal were independent of the size of the response or varied slightly with it, suggesting that the climbing fibres involved innervated territories whose electrotonic distance from the recording site were either the same or slightly different. 6. Interactions between two all-or-none steps of the graded post-synaptic potential evoked in multiply innervated cells by juxtafastigial and olivary stimulations revealed either a very weak or a very marked shunting effect between synapses of the two climbing fibres involved. 7. These results indicate that the over-all distribution of climbing fibre synapses on multiply innervated Purkinje cells is not grossly abnormal and that two fibres contacting a given cell can be either intermingled on the same dendrites, or segregated on distinct dendritic branches. 8. In general, the present study does not suggest the existence of a strong competition among climbing fibres innervating each Purkinje cell during development at least when granule cells are absent.

Animals↗

Genetic evidence for the bidirectional modulation of synaptic plasticity in the prefrontal cortex by D1 receptors.

To address the role of D1 receptors in the medial prefrontal cortex, we combined pharmacological and genetic manipulations to examine long-term synaptic potentiation (LTP)/long-term synaptic depression (LTD) in brain slices of rats and mice. We found that the D1 antagonist SCH23390 selectively blocked the maintenance but not the induction of LTP in the prefrontal cortex. Conversely, activation of D1 receptors facilitated the maintenance of LTP, and this effect is impaired in heterozygous D1 receptor knockout mice. Low-frequency stimulation induced a transient depression in the medial prefrontal cortex. This depression could be transformed into LTD by coapplication of dopamine. Coapplication of dopamine, however, shows no facilitating effect on LTD in heterozygous D1 receptor knockout mice. These results provide pharmacological and genetic evidence for a role of D1 receptors in the bidirectional modulation of synaptic plasticity in the medial prefrontal cortex. The absence of this modulation in heterozygous knockout mice shows that a dysregulation of dopamine receptor expression levels can have dramatic effects on synaptic plasticity in the prefrontal cortex.

Animals↗

Long-term potentiation of synaptic transmission in the hippocampus induced by a bee venom peptide.

Several neurotoxins have been isolated from bee venom. One of these, the mast cell degranulating peptide (MCD), releases histamine from mast cells and on central administration produces arousal at low concentrations and convulsions at higher doses. These effects are mediated through specific high-affinity binding sites which are concentrated in cortical structures, notably the hippocampus. This structure appears to be the source of changes in the electrocorticogram that follow injections of MCD into the cerebral ventricle, and which induce a quasi-permanent hippocampal theta rhythm in the motionless rat alternating with epileptiform spike waves. We report here that brief application of MCD to the CA1 region of hippocampal slices induces long-term potentiation, that is, a long-lasting increase in the efficacy of synaptic transmission. This potentiation seems to be indistinguishable from the classical LTP produced by trains of high-frequency electrical stimulation and considered to be related in some way to memory. Using binding to synaptosomal membranes and radioimmunoassay techniques, we have also found an endogenous peptide equivalent of MCD in brain extracts. This raises the possibility that a MCD-like peptide may be important in long-term potentiation.

2-Amino-5-phosphonovalerate↗

The NMDA antagonist, MK-801, suppresses long-term potentiation, kindling, and kindling-induced potentiation in the perforant path of the unanesthetized rat.

Antagonism of NMDA-mediated transmission by MK-801 has been shown to block long-term potentiation (LTP) in vitro and delay electrical kindling of the amygdala. The present experiment sought to examine the relationship between synaptic potentiation of the perforant path-granule cell synapse and development of perforant path kindling. MK-801 (0.1 and 1.0 mg/kg) blocked induction of LTP of the perforant path in the unanesthetized animal measured 24 h after train delivery. The 1.0 mg/kg dosage also increased afterdischarge (AD) thresholds, delayed kindling development from daily stimulation of the perforant path (means = 8.82 +/- 1.19 and 22.9 +/- 3.66 sessions to the first stage 5 seizure), and increased AD durations. Kindling produced a significant potentiation of the EPSP (47%) and population spike (49%) after the first evoked AD in control animals. No significant enhancement of either component of the field potential was observed in MK-801-treated animals. Animals treated with this dosage of MK-801, did, however, kindle in the absence of potentiation at this synapse. It was concluded that although NMDA-mediated potentiation may facilitate kindling, synaptic potentiation does not appear to be a critical requirement for kindling to develop. These findings support the notion that development of the burst response and not synaptic enhancement may be the critical physiological alteration that underlies the kindling phenomenon.

Amygdala↗