Developmental changes in the expression of calbindin and potassium-channel subunits Kv3.1b and Kv3.2 in mouse Renshaw cells.

One class of spinal interneurons, the Renshaw cells, is able to discharge at very high frequencies in adult mammals. Neuronal firing at such high frequencies requires voltage-gated potassium channels to rapidly repolarize the membrane potential after each action potential. We sought to establish the pattern of expression of calbindin and potassium channels with Kv3.1b and Kv3.2 subunits in Renshaw cells at different developmental stages of postnatal mice. The pattern of expression of calbindin changed dramatically during early postnatal development. An adult pattern of calbindin reactive neurons started to emerge from postnatal day 10 to postnatal day 14, with cells in laminae I and II of superficial dorsal horn and the ventral lamina VII. Renshaw cells were identified immunohistochemically by their expression of calbindin and their location in the ventral horn of the spinal cord. Western blot results of the lumbar spinal cord showed that Kv3.1b expression became faintly evident from postnatal day 10, reached a maximum at postnatal day 21 and was maintained through postnatal day 49. Double labeling results showed that all Renshaw cells expressed Kv3.1b weakly from postnatal day 14, and strongly at postnatal day 21. Western blot results showed that Kv3.2 expression became detectable in the lumbar cord from postnatal day 12, and increased steadily until reaching an adult level at postnatal day 28. In contrast to the Kv3.1b results, Kv3.2 was not expressed in Renshaw cells, although some neurons located at laminae VIII and VI expressed Kv3.2. We conclude that Renshaw cells express Kv3.1b but not Kv3.2 from postnatal day 14.

The phosphoinositide 3-kinase and p70 S6 kinase regulate long-term potentiation in hippocampal neurons.

The mechanisms by which long-term changes in synaptic efficacy (e.g., long-term potentiation) are maintained are not well understood. There is evidence that reorganization of the neuronal actin cytoskeleton is important for consolidation of long-term potentiation. In non-neuronal cells, phosphoinositide 3-kinase and p70 S6 kinase have been shown to regulate actin polymerization. We have investigated the subcellular localization of these enzymes in cultured hippocampal pyramidal neurons and their possible role in hippocampal long-term potentiation. Immunohistochemical analysis revealed enrichment of both enzymes in the growth cones and filopodia of extending neurites, whereas p70 S6 kinase was also present at the soma. Antibodies to the phosphorylated form of p70 S6 kinase confirmed its activity in these locations. Interestingly, both enzymes displayed strong colocalization with F-actin in discrete regions of developing neurites. In hippocampal slices, the maintenance of long-term potentiation was attenuated by either rapamycin or 2-(4-morpholinyl)-8-phenyl-1(4H)-1-benzopyran-4-one, inhibitors of p70 S6 kinase and phosphoinositide 3-kinase, respectively. Our findings provide evidence for a novel biochemical pathway involving phosphoinositide 3-kinase and p70 S6 kinase that is important for the maintenance of hippocampal long-term potentiation, possibly via regulation of actin dynamics.

The parahippocampal gyrus in Alzheimer's disease. Clinical and preclinical neuroanatomical correlates.

The human parahippocampal gyrus forms a large part of the limbic lobe along the ventromedial part of the temporal cortical mantle. It is a variable and complicated cortex in terms of structure, and the latter is aggravated further by interfaces with the anterior insula anteriorly and the cingulate gyrus and occipital lobe posteriorly. Additional complications relate to its lateral border with the temporal cortex and especially the sulcal configurations that define this junction. The rhinal sulcus, which separates parahippocampal and temporal cortices in other species, including the anthropoid apes, is either lacking or rudimentary in the human brain. Thus, defining this junction requires cytoarchitectural examination and precludes the use of mere inspection of sulcal existing patterns. The cortical areas that form the parahippocampal gyrus are vulnerable to pathological changes in Alzheimer's disease (AD), and its entorhinal and perirhinal subdivisions are both the most heavily damaged cortical areas and the focus for disease onset. The neurons that acquire neurofibrillary tangles (NFTs) occupy the junction of the isocortical mantle with the limbic cortical mantle, but share, or partially share, a vulnerability phenotype with large neurons in both domains. The differential expression of this phenotype across time creates the false impression of NFT spread in cross-sectional comparisons of AD brains. The questions of what this phenotype is and why it is expressed first in the perirhinal and entorhinal cortices of the parahippocampal gyrus are the central molecular biological/neuroanatomical questions in understanding the etiology of AD.

Long-term potentiation across rat cerebello-thalamic synapses in vitro.

We previously demonstrated that rat cerebello-thalamic synapses undergo an ultrastructural change, consistent with expression of long-term potentiation, in association with motor adaptation. The aim of these experiments was to determine if long-term potentiation can be expressed at these synapses physiologically. Excitatory post-synaptic potentials evoked by electrical stimulation of cut cerebello-thalamic afferents were recorded intracellularly from thalamic neurons in 17-24 day old rat brain slice preparations. The experimental protocol involved long periods of low frequency single-shock control stimuli interrupted by brief high frequency trains of conditioning stimuli. Conditioning at 100 Hz evoked long-term potentiation in 5/6 cells and long-term depression in 1/6 cells. Conditioning at 200 Hz was unsuccessful in evoking long-term potentiation but did evoke long-term depression in 1/3 cells and no change in 2/3 cells. We conclude that long-term potentiation can be evoked across rat cerebello-thalamic synapses in vitro.

Analysis of NMDA-independent long-term potentiation induced at CA3-CA1 synapses in rat hippocampus in vitro.

1. Excitatory postsynaptic currents (EPSCs) were evoked at synapses formed by Schaffer collaterals/commissural (CA3) axons with CA1 pyramidal cells using the rat hippocampal slice preparation. Long-term potentiation (LTP) was induced at these synapses using a pairing protocol, with 50 microM d,l-APV present in the artificial cerebrospinal fluid (ACSF). 2. Quantal analysis of the amplitudes of the control and conditioned EPSCs showed that the enhancement of synaptic strength was due entirely to an increase in quantal content of the EPSC. No change occurred in the quantal current. 3. These results were compared with those obtained from a previous quantal analysis of LTP induced in normal ACSF, where both quantal current and quantal content increased. The results suggest that calcium entering via NMDA receptors initiates the signalling cascade that results in enhanced AMPA currents because it is adding to cytoplasmic calcium from other sources to reach a threshold for this signalling pathway, or because calcium entering via NMDA receptors specifically activates this signalling pathway.

Ventromedial temporal lobe pathology in dementia, brain trauma, and schizophrenia.

The ventromedial temporal area contains numerous anatomical structures collectively or selectively involved in a wide range of neurological and psychiatric disorders. Collective involvement is exemplified best by Alzheimer's disease where a host of anatomical structures and a host of cognitive and behavioral changes are manifested. Selective disease of the amygdala can yield deficits in the ability to judge and evaluate emotional expressions. While memory functions are nearly synonymous with the concept of ventromedial temporal area, they overshadow other functions associated with the diverse anatomical structures in this part of the brain. For example, it could be argued that in addition to output directed toward the hippocampal formation, the output of the ventromedial temporal area is equally strong to the ventral striatopallidal system of the basal forebrain. Denervation of these structures could be associated with the behavioral changes that occur in tandem with the memory-related changes of ventromedial temporal lobe pathology. Here we explore the anatomical and pathological correlate associated with ventromedial temporal area pathology and consider how these may impact on ventral striatopallidal conceptualizations. We conclude that ventromedial temporal area pathology deprives the basal forebrain of multimodal association information from the endstages of corticocortical sensory processing. This endstage information carries with it an analysis of real-time sensory awareness, historical-time or past sensory experiences, and decisions from hippocampal output structures regarding relevancy and novelty. In this sense, basal forebrain structures are in a unique position to regulate behavioral responses to a wide range of stimuli and to organize appropriate emotional, motor, autonomic, and endocrine responses to them.

Passive electrical properties of ventral horn neurons in rat spinal cord slices.

Recordings were made from large neurons located in the ventral horn of transverse spinal cord slices from young rats (7-15 days). Whole cell recordings were made simultaneously with two electrodes from the soma of these neurons, visualized using infra-red differential interference contrast optics. Positive identification of motoneurons could not always be achieved. The response of a neuron to a brief pulse of current delivered by one electrode, and recorded by the other electrode, were matched optimally to responses of a compartmental model of the same neuron with an identical current pulse as input. The compartmental model was based on a reconstruction of the neuron, using Biocytin staining. The compartmental model had three free parameters: specific membrane capacitance (Cm), membrane resistivity (Rm), and cytoplasmatic resistivity (Ri), all assumed to be uniform throughout the neuron. The experimental and model responses could be matched unequivocally for four neurons, giving Cm = 2.4 +/- 0.5 microF/cm2, Rm = 5.3 +/- 0. 9 kOmega/cm2, and Ri = 87 +/- 22 Omega/cm. No somatic shunt was required. For the remaining six neurons, a less perfect fit (but still within 95% confidence limits) was indicative of nonhomogeneous membrane properties. The electrotonic length of uncut dendrites was 0.85 +/- 0.14 lambda. The results resolve the issue of a somatic shunt conductance for motoneurons, relegating it to a microelectrode impalement artifact. They are consistent with previous reports on the electrical compactness of motoneurons to steady state currents and voltages. However, the much higher value of Cm (than the previously assumed 1 microF/cm2) implies much greater dendritic attenuation of fast synaptic potentials, and a much enhanced integrative response of motoneurons to synaptic potentials.

Passive electrical properties of ventral horn neurons in rat spinal cord slices.

Recordings were made from large neurons located in the ventral horn of transverse spinal cord slices from young rats (7-15 days). Whole cell recordings were made simultaneously with two electrodes from the soma of these neurons, visualized using infra-red differential interference contrast optics. Positive identification of motoneurons could not always be achieved. The response of a neuron to a brief pulse of current delivered by one electrode, and recorded by the other electrode, were matched optimally to responses of a compartmental model of the same neuron with an identical current pulse as input. The compartmental model was based on a reconstruction of the neuron, using Biocytin staining. The compartmental model had three free parameters: specific membrane capacitance (Cm), membrane resistivity (Rm), and cytoplasmatic resistivity (Ri), all assumed to be uniform throughout the neuron. The experimental and model responses could be matched unequivocally for four neurons, giving Cm = 2.4 +/- 0.5 microF/cm2, Rm = 5.3 +/- 0. 9 kOmega/cm2, and Ri = 87 +/- 22 Omega/cm. No somatic shunt was required. For the remaining six neurons, a less perfect fit (but still within 95% confidence limits) was indicative of nonhomogeneous membrane properties. The electrotonic length of uncut dendrites was 0.85 +/- 0.14 lambda. The results resolve the issue of a somatic shunt conductance for motoneurons, relegating it to a microelectrode impalement artifact. They are consistent with previous reports on the electrical compactness of motoneurons to steady state currents and voltages. However, the much higher value of Cm (than the previously assumed 1 microF/cm2) implies much greater dendritic attenuation of fast synaptic potentials, and a much enhanced integrative response of motoneurons to synaptic potentials.

Long-term plasticity at excitatory synapses on aspinous interneurons in area CA1 lacks synaptic specificity.

The synaptic specificity of long-term potentiation (LTP) was examined at synapses formed on aspinous dendrites of interneurons whose somata were located in the pyramidal cell layer of hippocampal area CA1. Intracellular recordings from slices prepared from rats were used to monitor excitatory postsynaptic potentials (EPSPs) elicited by extracellular stimulation in stratum radiatum. Two synaptic inputs were evoked at 0.5 Hz by stimulating axons adjacent to stratum pyramidale and s. lacunosum-moleculare. After obtaining baseline recordings (>/=10 min), one of the EPSPs was conditioned. The protocol involved tetanic stimulation, sometimes combined with somatic depolarization. Low-frequency stimulation of the two pathways was then resumed and EPSPs were recorded for <30 min. We observed both homosynaptic and heterosynaptic changes in synaptic strength. LTP and long-term depression (LTD) were seen in both pathways and all possible combinations of changes in the two EPSPs were observed, including heterosynaptic LTP associated with either homosynaptic LTP or LTD. Intracellular 1,2-bis (2-aminophenoxy)-ethane-N,N,N',N'-tetraacetic acid (10 mM) abolished alterations in synaptic strength. When axons in s. radiatum synapse onto a spiny pyramidal cell, synaptic specificity of LTP is preserved. However the results obtained from aspinous interneurons show that synaptic specificity of LTP is lost. These results are consistent with the hypothesis that spines provide postsynaptic mechanism(s) for conferring specificity to LTP.

Statistical analysis of amplitude fluctuations in EPSCs evoked in rat CA1 pyramidal neurones in vitro.

1. EPSCs were evoked in CA1 pyramidal neurones of young rats in vitro by extracellular stimulation of axons in a restricted stratum radiatum field, and were recorded using the whole-cell technique. 2. Quantal fluctuations in EPSC amplitude could be demonstrated for nineteen of fifty EPSCs analysed. Quantal currents (at the soma) ranged from 2.6 to 9.5 pA (after correction for the access resistance) with a mean of 4.0 +/- 2.0 pA. 3. Quantal variance was negligible for the majority (13/19) of the EPSCs. However, a large quantal variance (with a coefficient of variation > 0.4) is one possible reason why a large number of the EPSCs (29/50) could not be shown to have quantal fluctuations. 4. The statistical pattern of fluctuations in the amplitude of the majority of the quantal EPSCs (18/19) could not be described by conventional models of transmitter release. 5. The time course of the EPSC and a compartmental model of CA1 pyramidal neurones were used to calculate synaptic location. The quantal current (at the soma) was independent of the electrotonic location of the synapse at which it was evoked. The peak quantal conductance generating each quantal current ranged from 0.5 to 6.8 nS (mean 1.3 +/- 1.4 nS), its magnitude increasing with distance from the soma. The mean peak conductance is likely to be generated by the opening of at least 60-160 AMPA channels.

Changes in quantal parameters of EPSCs in rat CA1 neurones in vitro after the induction of long-term potentiation.

1. Long-term potentiation (LTP) was induced in EPSCs evoked in CA1 pyramidal neurones of young rats in vitro by extracellular stimulation of stratum radiatum. Low frequency stimulation was paired with postsynaptic depolarization to induce LTP, using whole-cell recording techniques. 2. Sufficient control and potentiated records were obtained under stable recording conditions to allow a quantal analysis of eleven EPSCs. The fluctuations in amplitude of all eleven EPSCs were quantized before conditioning stimulation, and they remained quantized after LTP induction, usually with an increased quantal variance. 3. Quantal current was increased by conditioning for nine out of eleven EPSCs. The increase in quantal current was correlated with the percentage increase in the EPSC. For only two EPSCs could the entire potentiation be attributed to an increase in quantal current. 4. The amplitude fluctuations of five control EPSCs could be described by binomial statistics, but after conditioning the binomial description held for only one of these EPSCs. For this EPSC, conditioning caused the release probability to increase from 0.39 +/- 0.05 to 0.47 +/- 0.02. 5. Quantal content was increased by conditioning stimulation for ten out of eleven EPSCs. The increase in quantal content was correlated with the percentage increase in the EPSC. However, for only four EPSCs could the entire potentiation be attributed to an increase in quantal content. 6. Most EPSCs were evoked with a high proportion of response failures. The probability of response failures decreased in eight out of eleven EPSCs following the induction of LTP. There was a negative correlation between the change in the probability of response failures and the amount of LTP. 7. The minimal number of sites at which transmission occurred increased for ten out of eleven EPSCs following LTP induction. Increases in the minimal number of active sites following conditioning were associated with decreases in the probability of response failures for seven out of eleven EPSCs. 8. The induction of LTP usually resulted in changes in the time course of the EPSCs. Cable analysis using a passive compartmental model of a CA1 pyramidal cell suggested that these time course changes were associated with shifts in the average electrotonic location of the active sites following LTP induction, rather than being caused by an increased duration of synaptic current. 9. LTP expression involves postsynaptic modifications to enhance the synaptic current at active sites. New sites are recruited, and our data cannot be used to determine if this is a result of a pre- or a postsynaptic change. Evidence for an increase in release probability was found for one EPSC.

The role of GABAA and GABAB receptors in presynaptic inhibition of Ia EPSPs in cat spinal motoneurones.

1. The role of GABAA and GABAB receptors in presynaptic inhibition was studied by examining the effect of local application of antagonists by ionophoresis during intracellular recording of presynaptic inhibition of compound and unitary group Ia afferent excitatory postsynaptic potentials (EPSPs) in gastrocnemius motoneurones. 2. Ionophoresis of the GABAA antagonist bicuculline methochloride (BMC) was found to block presynaptic inhibition of both compound and unitary EPSPs by up to 85%. BMC also substantially reduced, and occasionally abolished, the late part of the inhibitory postsynaptic potential (IPSP) evoked in motoneurones by the conditioning stimulation. The early part of this IPSP was found to be sensitive to ionophoresis of strychnine hydrochloride. 3. Ionophoresis of 2-OH-saclofen caused a reduction in presynaptic inhibition of compound EPSPs by 5-25% but had no effect on the IPSP evoked in motoneurones by the conditioning stimulation. 4. Ionophoresis of the GABAB antagonist (-)-baclofen reduced the amplitude of unconditioned EPSPs; however it had little effect on presynaptic inhibition. 5. It was concluded that at the Ia afferent-motoneurone synapse presynaptic inhibition is mediated primarily through the activation of GABAA receptors. The activation of GABAB receptors appears to play only a minor role in presynaptic inhibition at this synapse. This contrasts with the relative ease with which (-)-baclofen can reduce transmitter release from Ia afferent terminals and suggests that the receptors activated by (-)-baclofen are predominantly extrasynaptic.

Mechanisms of presynaptic inhibition studied using paired-pulse facilitation.

An investigation was made of the effect of presynaptic inhibition on paired-pulse facilitation (PPF) of group Ia afferent excitatory postsynaptic potentials (EPSPs). The main finding from this study was that PPF was enhanced during presynaptic inhibition of compound Ia EPSPs. This increase in PPF is identical to that seen at other synapses when the probability of transmitter release is decreased by lowering the extracellular calcium or raising the extracellular magnesium concentration, providing unequivocal evidence that presynaptic inhibition is associated with a decrease in the probability of transmitter release. Further, by analogy with the effects of reduced calcium influx on PPF at other synapses, the results support the idea that presynaptic inhibition is associated with reduced calcium influx into nerve terminals.

The time course and amplitude of EPSPs evoked at synapses between pairs of CA3/CA1 neurons in the hippocampal slice.

Unitary EPSPs were evoked in CA1 pyramidal neurons by activation of single CA3 pyramidal neurons. Seventy-one EPSPs were recorded. The peak amplitudes of these EPSPs ranged from 30 to 665 microV with a mean of 131 microV. Rise times and half-widths were measured, the means +/- SD being 3.9 +/- 1.8 and 19.5 +/- 8.0 msec, respectively. The time courses of these EPSPs were consistent with a brief synaptic current at a localized electrotonic region of the dendritic tree followed by passive spread of current to the soma. EPSPs varied in amplitude from trial to trial. Sufficient records were collected for 12 EPSPs to demonstrate that this variation was greater than could be accounted for by baseline noise. The amplitude variations of one EPSP were reliably resolved from the background noise, and this EPSP fluctuated between 4 discrete amplitudes (including failures) separated by a quantal increment of 278 microV.

Evaluation of long-term potentiation of small compound and unitary EPSPs at the hippocampal CA3-CA1 synapse.

Long-term potentiation (LTP) was evaluated for small monosynaptic CA3-mediated EPSPs in CA1 neurons in the guinea pig hippocampal slice. Small EPSPs included those elicited by stimulation of Schaffer axon collaterals of several CA3 neurons (160-480 microV amplitude, n = 40 EPSPs in 40 neurons) and those elicited by stimulation of an individual CA3 neuron (89-563 microV amplitude, n = 14 EPSPs in 11 neurons). Various protocols were employed to induce LTP and were deemed successful as evaluated by recording sustained enhancement of the mean peak amplitude of conventionally elicited large compound EPSPs and extracellular field potentials. However, in 47 of 54 cases, tetanization did not lead to a potentiation of the small or unitary EPSPs. In 9 cases, it was possible to directly evaluate the compound EPSP (elicited by stimulating a group of CA3 neuron's axons) and the unitary EPSP (elicited by stimulating a single CA3 neuron) in the same CA1 neuron. The tetanization protocol was successful in inducing LTP in 7 of 9 of these CA1 neurons as evaluated by the compound EPSP but resulted in LTP for only 1 of 9 of the unitary EPSPs for the same neurons. One explanation for these results is a threshold mechanism controlling the expression of LTP. Although LTP induction occurred in most cases, it is proposed that a critical level of depolarization (achieved by the test activation of a sufficient number of CA3 neurons) is necessary so that the enhancement at the modified synapse is expressed.

Voltage dependence of Ia reciprocal inhibitory currents in cat spinal motoneurones.

1. Inhibitory postsynaptic currents (IPSCs) were recorded in voltage clamped posterior biceps or semitendinosus motoneurones of the cat during reciprocal inhibition. 2. Population IPSCs, recorded following stimulation of the whole quadriceps muscle nerve, had an average time-to-peak of 0.51 +/- 0.02 ms (+/- S.E.M., n = 22) and decayed exponentially, with an average time constant of 0.99 +/- 0.04 ms (at 37 degrees C) at resting membrane potentials. 3. Unitary IPSCs, recorded following spike-triggered averaging from an identified reciprocal inhibitory interneurone, had amplitudes of 120-220 pA with an average time-to-peak of 0.40 +/- 0.06 ms (n = 5). The decay of these unitary currents was exponential, with an average time constant of 0.82 +/- 0.07 ms (at 37 degrees C) at resting membrane potentials. 4. The time course of IPSCs was unaffected by either alpha-chloralose or pentobarbitone at concentrations necessary for deep anaesthesia. 5. The peak synaptic current varied linearly with the membrane potential over the range -90 to -30 mV, and had an average reversal potential of -80.7 +/- 1.5 mV (+/- S.E.M., n = 6) when measured using KCH3SO4-filled electrodes. 6. The reversal potential for the IPSC was used to calculate [Cl-]i. This was estimated to be 6.5 mM assuming that the inhibitory synaptic current was mediated purely by Cl- ions. 7. The rate at which synaptic currents decayed was exponentially dependent on the postsynaptic membrane potential, the decay time constant increasing e-fold for a 91 mV depolarization. This result was independent of [Cl-]i or of the magnitude of the synaptic conductance and was interpreted as a voltage dependence of the glycine channel open time. 8. The average unitary peak conductance was 9.1 +/- 1.7 nS (+/- S.E.M., n = 5), corresponding to the opening of approximately 200 glycine-activated postsynaptic channels following neurotransmitter release from a single Ia reciprocal interneurone.

Reduction by general anaesthetics of group Ia excitatory postsynaptic potentials and currents in the cat spinal cord.

1. The effects of thiopentone and halothane on excitatory synaptic transmission at group Ia afferent synapses on lumbosacral motoneurones were studied in the anaesthetized or decerebrate cat. 2. Thiopentone (10 mg kg-1) infused on a background of light pentobarbitone anaesthesia caused a decrease in single-fibre monosynaptic group Ia excitatory postsynaptic potentials (EPSPs) of between 0 and 24%. A step increase in inspired halothane concentration in the range 0.7-0.9% produced a decrease in EPSP amplitude of between 0 and 31%. These effects were reversible when the anaesthetic level was reduced. 3. Fluctuation analysis of selected single-fibre group Ia EPSPs revealed that these effects could be accounted for by a decrease in the probability of occurrence of EPSPs of larger amplitude, and an increase in the probability of occurrence of EPSPs of smaller amplitude. The mean separation between discrete amplitudes was not altered by either anaesthetic agent. 4. EPSPs whose time course indicated a somatic site of origin were voltage clamped to study the effect of the anaesthetics on the time course of the synaptic currents. Neither thiopentone nor halothane produced a consistent effect on the time constant of decay of the current, although they both depressed its peak amplitude. 5. The results are interpreted as indicating a presynaptic site of action of both anaesthetics at the concentrations studied: the probability of release of neurotransmitter is reduced, without any detectable change in the mean duration of the postsynaptic conductance increase. These findings are discussed in relation to the mechanisms of action of anaesthetics on exocytosis and presynaptic inhibition.

Amplitude fluctuations in small EPSPs recorded from CA1 pyramidal cells in the guinea pig hippocampal slice.

EPSPs have been evoked in CA1 pyramidal cells by (1) activation of single CA3 neurons (unitary EPSPs), and (2) low-intensity stimuli to the CA1 stratum radiatum. Five unitary EPSPs were obtained; their mean peak amplitudes ranged from 85 to 275 microV and 3 of the 5 showed fluctuations in amplitude that were too great to be attributed to baseline noise. After subtraction of the variance due to the noise, these EPSPs had coefficients of variation much higher than those reported for variability in the quantal EPSP in other preparations. These results suggest that intermittent transmitter release is a major cause of EPSP amplitude fluctuation at this synapse. A noise deconvolution technique based on a nonrestrictive model of transmitter release was applied to the EPSPs obtained in this study. For 2 of the EPSPs evoked by stratum radiatum stimulation, the amplitudes fluctuated between discrete values that were sufficiently separated with respect to the noise to be resolved by the deconvolution procedure. Quantal increments of 224 and 193 microV were determined for the 2 EPSPs.