Summation Of Excitatory Postsynaptic Potentials Research Articles

Activity-dependent properties of synaptic transmission at two classes of connections made by rat neocortical pyramidal axons in vitro.

1. To compare the dynamics of synaptic transmission at different types of connection, dual intracellular recordings were made from pairs of neurones in slices of adult rat neocortex. Excitatory postsynaptic potentials (EPSPs) were elicited by single spikes, spike pairs and brief spike trains in presynaptic pyramidal cells and responses recorded in postsynaptic pyramidal cells and in interneurones. 2. Pyramid-pyramid EPSPs were strongly voltage dependent and this resulted in a range of paired pulse effects. At thirty-two of sixty-nine pyramid-pyramid connections, the 2nd EPSP was the same shape as the 1st, indicating minimal interaction between active synapses. In these thirty-two connections, paired pulse depression (PPD) was apparent (2nd EPSP integral 46 +/- 21% of the 1st, at 5-20 ms), which recovered within 60-70 ms. 3. In eleven additional pyramid-pyramid pairs, the 2nd EPSP was also the same shape as the 1st, but paired pulse facilitation (PPF, 149 +/- 32%) decaying within 50-60 ms was apparent. Even these connections displayed frequency-dependent depression, however, as 3rd EPSPs were smaller than 1st EPSPs at intervals < 100 ms. 4. At twenty-five pyramid-pyramid connections, 2nd EPSPs were broader than 1st EPSPs and in sixteen of these, voltage- and NMDA receptor-dependent enhancement was large enough to obscure the underlying PPD. PPD was revealed by postsynaptic hyperpolarization (4 pairs), N-methyl-D-aspartate (NMDA) receptor blockade (3 paris), or if Mg2+ was removed (in the one case studied). If synapse location allowed significant depolarization of one active site by another, voltage-dependent enhancement could produce supralinear EPSP summation and overcome PPD. Third EPSPs were, however, consistently smaller than 1st EPSPs. 5. In striking contrast, profound frequency-dependent facilitation, independent of voltage or NMDA receptors was seen at fifteen connections involving two classes of postsynaptic interneurones. 6. At these pyramid-interneurone connections, facilitation of the 2nd EPSP (655 +/- 380% at 5-20 ms) decayed rapidly, within 50-60 ms. Third and fourth EPSPs showed additional facilitation which decayed more slowly, within 90 ms and 2 s, respectively. Facilitation due to five to six spike trains was still apparent at 3 s. Therefore, once initiated by a brief high frequency spike train, facilitation was maintained at lower frequencies.

Role of temporal summation in age-related long-term potentiation-induction deficits.

Hippocampal long-term potentiation (LTP) is reduced in aged relative to young F-344 rats when peri-threshold stimulation protocols (several stimulus pulses at 100-200 Hz) are used. The present study was designed to examine the possibility that this LTP-induction deficit is caused by a reduced overlap of Schaffer-collateral inputs onto CA1 pyramidal cells (input cooperativity). This reduced input cooperativity would decrease the levels of postsynaptic depolarization during LTP induction, which might account for the age-related LTP deficit. Both behavioral data (Morris Water Maze) and electrophysiological data (intracellular recordings from hippocampal slices) were collected from adult and aged F-344 rats. To counter the effects of reduced input cooperativity, stimulus intensities were adjusted to elicit baseline excitatory postsynaptic potentials (EPSPs) of equivalent amplitude in aged and young rats. Contrary to expectations, however, an age-related LTP-induction deficit was still observed. Further evaluation of the electrophysiological data revealed that temporal summation of multiple EPSPs during high-frequency stimulation was impaired in the aged rats. Thus, despite the equalization across age groups of the baseline EPSP amplitudes, the cells of aged rats were less depolarized during the LTP-inducing stimulation than were those of young rats. This reduced total depolarization was not an artifact of the higher stimulus intensity used on aged animals, nor was it caused by a failure of aged rats' CA1 afferents to follow high-frequency stimulation. The present data therefore suggest that there is a deficit in the ability of aged rats' synapses to provide the sustained depolarization necessary to active the LTP-induction cascade.

Spatio-temporal summation of synaptic activity in visual cortical pyramidal cells in vitro

We investigated the spatio-temporal summation of excitatory postsynaptic potentials (EPSPs) in supragranular pyramidal cells of the rat extrastriate visual cortex. EPSPs were evoked orthodromically from different locations within the white matter (WM) via an 8-fold multi-electrode array. Stimuli were applied either sequentially from electrodes 1 to 8 or vice versa at defined interstimulus intervals (ISIs) or separately from each electrode. Maximum EPSP amplitudes were evoked from the WM just below the intracellularly recorded neuron. Even 800 μm lateral to this location, small EPSPs could be elicited. A sequential stimulation resulted in a large compound EPSP. In 79% ( n = 34) of the cells tested, the compound response was non-directional and could be predicted from responses evoked by single stimulation electrodes. However, 21% ( n = 9) of the neurons showed a non-linear spatial summation and a clear preference for the direction of the stimulation sequence. ISI-tuning curves revealed either a sharply tuned, a bandpass, a highpass or a lowpass characteristics for the non-directional as well as directional cells. This feature, together with the clear directional responses observed in some neurons, may be a correlate of the response preference to moving stimuli of cortical cells found in vivo.

Electrical stimulation of the human descending motor tracts at several levels.

The descending motor tracts were activated using a high voltage electrical stimulation technique at four levels: the motor cortex, brainstem (around the pyramidal decussation), and the first and sixth thoracic vertebral levels (T1, T6). Electromyographic activity was recorded from the tibialis anterior or extensor digitorum brevis muscles. Consistent motor action potentials could be evoked in all normal subjects. The conduction velocity of the descending tracts was estimated to be 62 to 79 m/s. The sum of synaptic delay and utilization time at the motoneurons (spinal delay time) was estimated to be 0.5 +/- 0.3 ms indicating a mono- or oligosynaptic connection. In patients with diffusely affected descending tracts, the technique showed slowed conduction along the descending tracts and prolonged spinal delay time which may include the time required for temporal summation of excitatory postsynaptic potentials as well as synaptic delay and utilization time. In patients with a localized lesion, localized conduction delay was found at the appropriate segment.

Frequency characteristics and nonlinear features of responses of cat dorsal horn neurons to random stimulation of cutaneous afferents

The system between cutaneous (suralis) afferents and dorsal horn neurons was studied for comparison with studies previously performed on the motor axon-Renshaw cell system, using the same methods. In anaesthetized or decerebrated cats, 27 dorsal horn neurons of segments L 5 to S 1 were recorded extracellularly in depths of 1–2.3 mm from cord dorsum. Cutaneous afferents in branches of the ipsilateral suralis nerve were stimulated with sequences of randomly occurring electrical pulses at two levels of mean rate. The responses of the dorsal horn neurons to the stimuli were evaluated in the frequency and time domain. Calculation of coherence, gain and phase functions (via spectral analysis) showed that the frequency response depended on the precise pattern on cell discharge and could vary from broad-band to low-pass or occasionally band-pass characteristics. There were minor differences in these characteristics with those of Renshaw cells. A special type of nonlinear analysis, using conditional peristimulus-time histograms, showed that the responses to test stimuli were facilitated, depressed or both by conditioning stimuli occurring some tens to a few hundred milliseconds before. Early and late response components could be conditioned individually and differently. Exponential fits to such conditioning curves yielded two time constants for depression (means of 21 and 94ms) and one for facilitation (14ms). Similar conditioning effects and time constants were previously found for the motor axon-Renshaw cell system although a few differences were apparent. By analogy, it is suggested that part of the long-lasting conditioning effects (with long time constants) are probably due to presynaptic mechanisms. The short time constants may result from a mixture of temporal summation of excitatory postsynaptic potentials and presynaptic facilitation of transmitter release.

Entladungscharakteristika der durch transkranielle Kortexreizung aktivierten motorischen Einheiten in den Handmuskeln des Menschen

Using concentric needle electrode recording from hand muscles (abductor digiti minimi, first dorsal interosseus, or abductor pollicis brevis muscle) the latencies of single motor unit potentials in response to threshold magnetic brain stimuli were studied under different conditions. It has been shown that the motor units activated by threshold brain stimuli had the lowest threshold for voluntary activation (see Fig. 1: A = vol. activated, B = brain stim.). Onset latencies of 23 motor unit potentials from different sites in the relaxed muscles of four healthy subjects ranged from 22.4 to 32.4 ms (average: 26.4 ms; SD: 2.80 ms) but proved to be relatively stable when stimulating and recording conditions were kept constant (variation < 0.5 ms, see poststimulus time histogram in Fig. 2). With concurrent contraction of an ipsilateral neighbouring or of the contralateral homologuous muscle the motor unit potentials from the relaxed target muscle jumped to an earlier latency by 1.2 to 1.7 ms (C in Fig. 3 and B-2 in Fig. 4). On one occasion another motor unit of higher threshold was alternatively activated by this procedure (B-3 in Fig. 4). Since the same procedures are known to enhance the compound muscle action potentials as recorded from the relaxed muscle with surface electrodes, the shorter latencies of single motor units are considered to be caused by a facilitatory influence on the motoneurones. A possible explanation for these latency shifts would be that the motor units discharge later in response to the brain stimulus induced repetitive corticospinal impulses when there is no facilitation, whereas during facilitation the firing level is reached earlier. When using threshold electrical brain stimuli, the same motor unit with the same latency as with magnetic stimulation was activated (B in Fig. 6) and it also jumped to an earlier latency by the mentioned facilitatory measures (C in Fig. 6). A similar latency shift was sometimes observed when it was possible to increase the stimulus intensity without recruiting additional motor units within the pick up area of the needle electrodes, so that the original motor unit potential remained identifiable (B in Fig. 5; stimulus still more enhanced in C of Fig. 5). When increasing the stimulus intensity, the number of active cortico-spinal neurones impinging on a motoneurone is likely to be increased. This enhances the spatial summation of excitatory postsynaptic potentials in a motoneurone and may also result in an earlier firing of the motoneurone in response to the stimulus induced descending activity, since then less temporal summation is needed. Repetitive high frequency cortico-spinal trains in response to single brain stimuli must be assumed from animal experiments and epidural spinal cord recordings in humans. The interval between the descending impulses was found to be in the order of 1.4 (1.0-1.8) ms and therefore is similar to the latency shift we observed in motor unit potentials.

Formation of retinotopic connections: selective stabilization by an activity-dependent mechanism.

During regeneration of the optic nerve in goldfish, the ingrowing retinal fibers successfully seek out their correct places in the overall retinotopic projection on the tectum. Chemospecific cell-surface interactions appear to be sufficient to organize only a crude retinotopic map on the tectum during regeneration. Precise retinotopic ordering appears to be achieved via an activity-dependent stabilization of appropriate synapses and is based upon the correlated activity of neighboring ganglion cells of the same receptive-field type in the retina. Four treatments have been found to block the sharpening process: (a) blocking the activity of the ganglion cells with intraocular tetrodotoxin (TTX), (b) rearing in total darkness, (c) correlating the activation of all ganglion cells via stroboscopic illumination and (d) blocking retinotectal synaptic transmission with alpha-bungarotoxin (alphaBTX). These experiments support a role for correlated visually driven activity in sharpening the diffuse projection and suggest that this correlated activity interacts within the postsynaptic cells, probably through the summation of excitatory postsynaptic potentials (EPSPs). Other experiments support the concept that effective synapses are stabilized: a local postsynaptic block of transmission causes a local disruption in the retinotectal map. The changes that occur during this disruption suggest that each arbor can move to maximize its synaptic efficacy. In development, initial retinotectal projections are often diffuse and may undergo a similar activity-dependent sharpening. Indirect retinotectal maps, as well as auditory maps, appear to be brought into register with the direct retinotopic projections by promoting the convergence of contacts with correlated activity. A similar mechanism may drive both the formation of ocular dominance patches in fish tectum and kitten visual cortex and the segregation of different receptive-field types in the lateral geniculate nucleus. Activity-dependent synaptic stabilization may therefore be a general mechanism whereby the diffuse projections of early development are brought to the precise, mature level of organization.

Neuromuscular transmission in the visceral muscle of locust oviduct

Innervation of the locust oviduct has been investigated with morphological and electro-physiological methods. Using Co 2+ and Ni 2+ labelling technique, it was found that G7 N2B 1 and B 2a nerves innervate the oviduct musculature. Ultrastructurally two different terminals could be distinguished: (a) nerve endings containing mainly clear vesicles forming neuromuscular junctions with the muscle fibers; and (b) nerve terminals containing electron-dense granules which showed only “synaptoid” structures, but failed to form junctions with the muscle cells. The neuromuscular junctions proved to be functioning, since it was possible to record intracellularly miniature excitatory postsynaptic potentials and excitatory postsynaptic potentials from the muscle cells. The distribution of the amplitudes of the miniature excitatory postsynaptic potentials suggests a multiterminal innervation. Following electrical stimulation of N2B nerve, excitatory postsynaptic potentials similar to those appearing spontaneously could be evoked. After repetitive stimulation, facilitation or summation of excitatory postsynaptic potentials was observed. The results obtained show that locust oviduct muscle has a double, motor and modulatory innervation.

Summation of excitatory postsynaptic potentials in hippocampal pyramidal cells.

The summation of excitatory postsynaptic potentials (EPSPs) generated in separate parts of the dendritic tree of hippocampal pyramidal cells has been investigated using the in vitro slice preparation. Two separate inputs with known synaptic location were used. The EPSP produced by simultaneous activation of the two inputs (observed sum) was compared to the algebraic sum of the individual EPSPs. Small-amplitude EPSPs (0.5-1.5 mV) added linearly. The shortest distance between the two synaptic groups was 75 micron. With larger amplitudes (greater than 2.5 mV), the EPSP summated nonlinearly. The nonlinear summation was reduced by moderate hyperpolarizations (2-10 mV) of the soma membrane. Also, large EPSPs (greater than 2.5 mV) summated linearly when the peak of the summed EPSP was brought close to the equilibrium potential for the inhibitory postsynaptic potential (IPSP) (EIPSP). When the EPSP peak was made more negative than the EIPSP, summation was again nonlinear but the algebraic sum was now smaller than the observed EPSP sum, i.e., the direction of the nonlinearity was reversed. EPSP summation was linear after the IPSP had been blocked by benzyl penicillin application. We conclude that separate EPSPs in hippocampal pyramids (minimal separation, 75 micron) add linearly but that the addition of an IPSP may complicate this picture. No evidence was found for interaction between the different populations of excitatory synapses.

Factors that control amplitude of EPSPs in dendritic neurons.

We have used a computer-based mathematical model of alpha-motoneurons and of group Ia synaptic input to them, based on anatomical and electrophysiological data from the cat spinal cord, in order to examine the effects of variations in neuron size and input resistance and of conductance magnitude and duration on the generation of excitatory postsynaptic potentials (EPSPs). The first set of calculations were designed to test the possible role of nonlinear EPSP summation in producing a differential distribution of posttetanic potentiation of group Ia EPSPs, described in the preceding paper (25; see also Refs. 26, 27). The results suggest that the negative correlations observed between the degree of posttetanic potentiation of Ia EPSPs and initial (pretetanic) EPSP amplitude as well as with the input resistance of the postsynaptic motoneurons can be explained in part by the inherent non-linearity between conductance change and the resultant potential change at chemical synapses. In a second set of calculations, we used the same model system to evaluate the effects produced by variations in neuronal membrane area, input resistance, and specific membrane resistivity, as well as of the density of excitatory synaptic input on the peak amplitude of EPSPs. With parameters constrained to match the properties of alpha-motoneurons and group Ia synaptic input, EPSP amplitudes were most sensitive to changes in synaptic density and were much less sensitive to alterations in neuron input resistance and specific membrane resistivity when synaptic density was constant.

Cross-Correlation Functions for a Neuronal Model

Cross-correlation functions, R(XY)(t,tau), are obtained for a neuron model which is characterized by constant threshold theta, by resetting to resting level after an output, and by membrane potential U(t) which results from linear summation of excitatory postsynaptic potentials h(t). The results show that: (1) Near time lag tau = 0, R(XY)(t,tau) = f(U) [theta-h(tau), t + tau] {h'(tau) + E(U) [u'(t + tau)]} for positive values of this quantity, where f(U)(u,t) is the probability density function of U(t) and E(U) [u'(t + tau)] is the mean value function of U'(t + tau). (2) Minima may appear in R(XY)(t,tau) for a neuron subjected only to excitation. (3) For large tau, R(XY)(t,tau) is given approximately by the convolution of the input autocorrelation function with the functional of point (1). (4) R(XY)(t,tau) is a biased estimator of the shape of h(t), generally over-estimating both its time to peak and its rise time.

Early prenatal development of cortical surface responses to visual stimuli in sheep

Cortical surface responses to electrical stimulation of the optic nerve were recorded in sheep fetuses between 55 and 124 days of gestation (term 145 days). The cortical response obtained in the youngest fetuses was a long-latency surface-positive wave, followed by a small negativity. Later during development the negativity increased in amplitude and dominated the response. This early developmental pattern of the visual response was similar to that of the somesthetic response. On basis of findings on the maturation of structure and function in the somesthetic cortex the genesis of the visual response is discussed. The hypothesis is put forward that, at its earliest appearance, the positive wave of the visual response is predominantly reflecting synchronous depolarization of developing corticopetal nerve terminals and later arises from summation of excitatory postsynaptic potentials of deep-seated cortical neurons. The surface negativity of the response is considered to reflect excitatory postsynaptic activation of neural elements in the superficial neocortex. At about 98 days of fetal age a short-latency component appeared in the response. It is suggested that this component is mediated through the specific optic pathways, whereas the earlier-appearing long-latency response is suggested to be mediated via the unspecific visual projection. During the succeeding development the two components apparently coalesced to build up a positive-negative response containing all elements of the adult form.

Non-linear summation of unit synaptic potentials in spinal motoneurones of the cat.

1. Monosynaptic excitatory post-synaptic potentials (EPSPs) produced in spinal motoneurones of the cat by stimulation of a single afferent fibre were recorded with intracellular electrodes.2. In total, seventy-three triceps surae motoneurones were studied with stimulation of thirty-six different afferent fibres.3. The mean amplitude of the EPSPs evoked by single afferent impulses ranged from 0.06 to 2.0 mV with an average of 0.27 mV.4. The mean number of unit EPSPs responding to a single afferent impulse (m) was calculated from the number of failures. The values ranged from 0.7 to more than 5. About 10% of the sample showed no failure of synaptic response in about 200 consecutive trials. The m values for these synaptic responses were estimated to range from 5 to 15.5. In the majority of tests, the observed amplitude fluctuations of monosynaptic EPSPs evoked by stimulation of a single fibre were less than those expected from Poisson's law. This discrepancy may be accounted for by non-linear summation of the unit EPSPs at dendritic synaptic sites.6. It is suggested that the synaptic responses initiated at different sites of a motoneurone may summate linearly at the soma, although summation of unit EPSPs is non-linear at individual synaptic sites.

Synaptic Transmission in the Sensory Relay Neurons of the Thalamus

This chapter emphasizes the characteristic stepwise summation of excitatory postsynaptic potentials (EPSPs) observed during the monosynaptic activation of thalamocortical relay (TCR) neurons by a specific sensory input. The special synaptic morphology of the thalamocortical relay (TCR) neurons facilitates the neurophysiological study of dendritic function in the neurons. The glomerular synapses play an important role in the high-safety synaptic transmission. The large EPSP is the synchronized summation of two smaller EPSPs. The smaller amplitude and fast decay of the EPSP could be due to the change in membrane conductance during the inhibitory postsynaptic potential (IPSP) produced by the first optic nerve (OT) shock. The OT-evoked monosynaptic EPSPs in lateral geniculate body (LGB) neurons were not infrequently observed to comprise several components, some of which behaved in an all-or-none manner and summated effectively to secure neuronal discharge. Thus, in TCR neurons, each dendrite participates in the glomerular synapses, and a glomerular complex behaves as an elementary depolarizing component of TCR cells.

ELECTROPHYSIOLOGY OF THE FETAL SPINAL CORD. II. INTERACTION AMONG PERIPHERAL INPUTS AND RECURRENT INHIBITION.

Interactions of peripheral inputs to the motoneuron of the kitten fetus as young as 3 weeks prenatal were studied by reflex discharge from the ventral root as well as by recording from single motoneurons. Facilitation was found between two synergists in fetuses 1 to 2 weeks before birth. Intracellular recording showed that the facilitation could be explained by summation of excitatory postsynaptic potentials. Inhibition was found between antagonists in the fetuses 2 to 3 weeks before birth and was accompanied by inhibitory postsynaptic potentials. Recurrent inhibition was very powerful in the fetal spinal cord as shown by large motoneuron hyperpolarization by antidromic stimulation. Cells presumed to be "Renshaw cells" and which responded to both ortho- and antidromic stimulation with repetitive firing were shown in the 2 weeks prenatal fetus. These results lead to the conclusion that there is considerable effective synaptic connection of afferent collaterals already established by the later stage of intrauterine life and that this may be achieved independently of external stimuli.