Time Course Of Excitatory Postsynaptic Potentials Research Articles

Prolonged time course of population excitatory postsynaptic potentials in motoneurons of chronic stroke survivors.

Hyperexcitability of spinal motoneurons may contribute to muscular hypertonia after hemispheric stroke. The origins of this hyperexcitability are not clear, but we hypothesized that prolongation of the Ia excitatory postsynaptic potential (EPSP) in spastic motoneurons may be one potential mechanism, by enabling more effective temporal summation of Ia EPSPs, making action potential initiation easier. Thus, the purpose of this study is to quantify the time course of putative EPSPs in spinal motoneurons of chronic stroke survivors. To estimate the EPSP time course, a pair of low-intensity electrical stimuli was delivered sequentially to the median nerve in seven hemispheric stroke survivors and in six intact individuals, to induce an H-reflex response from the flexor carpi radialis muscle. H-reflex response probability was then used to quantify the time course of the underlying EPSPs in the motoneuron pool. A population EPSP estimate was then derived, based on the probability of evoking an H-reflex from the second test stimulus in the absence of a reflex response to the first conditioning stimulus. Our experimental results showed that in six of seven hemispheric stroke survivors, the apparent rate of decay of the population EPSP was markedly slower in spastic compared with contralateral (stroke) and intact motoneuron pools. There was no significant difference in EPSP time course between the contralateral side of stroke survivors and control subject muscles. We propose that one potential mechanism for hyperexcitability of spastic motoneurons in chronic stroke survivors may be associated with this prolongation of the Ia EPSP time course. Our subthreshold double-stimulation approach could provide a noninvasive tool for quantifying the time course of EPSPs in both healthy and pathological conditions. NEW & NOTEWORTHY Spastic motoneurons in stroke survivors showed a prolonged Ia excitatory postsynaptic potential (EPSP) time course compared with contralateral and intact motoneurons, suggesting that one potential mechanism for hyperexcitability of spastic motoneurons in chronic stroke survivors may be associated with this prolongation of the Ia EPSP time course.

Estimating the time course of population excitatory postsynaptic potentials in motoneurons of spastic stroke survivors.

Hyperexcitable motoneurons are likely to contribute to muscle hypertonia after a stroke injury; however, the origins of this hyperexcitability are not clear. One possibility is that the effective duration of the Ia excitatory postsynaptic potential (EPSP) is prolonged, increasing the potential for temporal summation of EPSPs, making action potential initiation easier. Accordingly, the purpose of this study was to quantify the time course of EPSPs in motoneurons of stroke survivors. The experimental protocol, which was based on parameters derived from simulation, involved sequential subthreshold electrical stimuli delivered to the median nerve of hemispheric stroke survivors. The resulting H-reflex responses were recorded in the flexor carpi radialis muscle. H-reflex response probability was then used to quantify the time course of the underlying EPSPs in the motoneuron pool. A population EPSP was estimated based on the probability of evoking an H reflex from the second electrical stimulus in the absence of a reflex response to the first stimulus. The accuracy of this time-course estimate was quantified using a computer simulation that explored a range of feasible EPSP parameters. Our experimental results showed that in all five hemispheric stroke survivors the rate of decay of the population EPSP was consistently slower in spastic compared with the contralateral motoneuron pools. We propose that one potential mechanism for hyperexcitability of motoneurons in spastic stroke survivors may be linked to this prolongation of the Ia EPSP time course. Our subthreshold double-stimulation approach also provides a noninvasive tool for quantifying the time course of EPSPs in both healthy and pathological conditions.

Activation of metabotropic glutamate receptors improves the accuracy of coincidence detection by presynaptic mechanisms in the nucleus laminaris of the chick

Interaural time difference (ITD) is a major cue for localizing a sound source and is processed in the nucleus laminaris (NL) in birds. Coincidence detection (CD) is a crucial step for processing ITD and critically depends on the size and time course of excitatory postsynaptic potentials (EPSPs). Here, we investigated a role of metabotropic glutamate receptors (mGluRs) in the regulation of EPSP amplitude and CD in the NL of chicks. A non-specific agonist of mGluRs ((±)-1-aminocyclopentane-trans-1,3-dicarboxylic acid; t-ACPD) reduced the amplitude and extent of depression of excitatory postsynaptic currents (EPSCs) during a stimulus train, while the paired pulse ratio and coefficient of variation of EPSC amplitude were increased. In contrast, the amplitudes of spontaneous EPSCs were not affected, but the frequency was reduced. Thus, the effects of t-ACPD were presynaptic and reduced the release of neurotransmitter from terminals in the NL. Expression of group II mGluRs was graded along the tonotopic axis and was stronger towards the low frequency region in the NL. Both group II (DCG-IV) and group III (l-AP4) specific agonists reduced EPSC amplitude by presynaptic mechanisms, and the reduction was larger in the low frequency region; however, we could not find any effects of group I-specific agonists on EPSCs. The reduced EPSP amplitude in DCG-IV improved CD. A specific antagonist of group II mGluRs (LY341495) increased the amplitude of both EPSCs and EPSPs and enhanced the depression during a stimulus train, indicating constitutive activation of mGluRs in the NL. These observations indicate that mGluRs may work as autoreceptors and regulate EPSP size to improve CD in the NL.

Involvement of R‐type Ca2+ channels in neurotransmitter release from spinal dorsolateral funiculus terminals synapsing motoneurons

Molecular studies have revealed the presence of R-type voltage-gated Ca(2+) channels at pre- and postsynaptic regions; however, no evidence for the participation of these channels in transmitter release has been presented for the spinal cord. Here we characterize the effects of SNX-482, a selective R channel blocker, on the monosynaptic excitatory postsynaptic potentials (EPSPs) evoked in motoneurons by stimulation of dorsolateral funiculus (DLF) terminals in a slice preparation from the adult turtle spinal cord. SNX-482 inhibited neurotransmission in a dose-dependent manner, with an IC(50) of approximately 9 +/- 1 nM. The EPSP time course and membrane time constant of the motoneurons were not altered, suggesting a presynaptic mechanism. The toxin inhibited the residual component of the EPSPs recorded in the presence of N- and P/Q-type Ca(2+) channel blockers, strongly suggesting a role for the R channels in neurotransmission at the spinal cord DLF terminals. Consistently with this, RT-PCR analysis of turtle spinal cord segments revealed the expression of the Ca(V)2.3 pore-forming (alpha(1E)) subunit of R channels, whereas the use of anti-alpha(1E)-specific antibodies resulted in its localization in the DLF fibers as demonstrated by immunohistochemistry coupled with laser confocal microscopy.

Factors determining the precision of the correlated firing generated by a monosynaptic connection in the cat visual pathway

Across the visual pathway, strong monosynaptic connections generate a precise correlated firing between presynaptic and postsynaptic neurons. The precision of this correlated firing is not the same within thalamus and visual cortex. While retinogeniculate connections generate a very narrow peak in the correlogram (peak width < 1 ms), the peaks generated by geniculocortical and corticocortical connections have usually a time course of several milliseconds. Several factors could explain these differences in timing precision such as the amplitude of the monosynaptic EPSP (excitatory postsynaptic potential), its time course or the contribution of polysynaptic inputs. While it is difficult to isolate the contribution of each factor in physiological experiments, a first approximation can be done in modelling studies. Here, we simulated two monosynaptically connected neurons to measure changes in their correlated firing as we independently modified different parameters of the connection. Our results suggest that the precision of the correlated firing generated by strong monosynaptic connections is mostly determined by the EPSP time course of the connection and much less by other factors. In addition, we show that a polysynaptic pathway is unlikely to emulate the correlated firing generated by a monosynaptic connection unless it generates EPSPs with very small latency jitter.

Spatiotemporal Patterns of Dorsal Root–Evoked Network Activity in the Neonatal Rat Spinal Cord: Optical and Intracellular Recordings

Spatiotemporal patterns of dorsal root-evoked potentials were studied in transverse slices of the rat spinal cord by monitoring optical signals from a voltage-sensitive dye with multiple-photodiode optic camera. Typically, dorsal root stimulation generated two basic waveforms of voltage images: dual-component images consisting of fast, spike-like signal followed by a slow signal in the dorsal horn, and small, slow signals in the ventral horn. To qualitatively relate the optical signals to membrane potentials, whole cell recordings were combined with measurements of light absorption in the area around the soma. The slow optical signals correlated closely with subthreshold postsynaptic potentials in all regions of the cord. The spike-like component was not associated with postsynaptic action potentials, suggesting that the fast signal was generated by presynaptic action potentials. Firing in a single neuron could not be detected optically, implying that local voltage images originated from synchronously activated neuronal ensembles. Blocking glutamatergic synaptic transmission inhibited excitatory postsynaptic potentials (EPSPs) and significantly reduced the slow optical signals, indicating that they were mediated by glutamatergic synapses. Suppressing glycine-mediated inhibition increased the amplitude of both optical signals and EPSPs, while blocking GABA(A) receptor-mediated synapses, increased the amplitude and time course of EPSPs and prolonged the duration of voltage images in larger areas of the slice. The close correlation between evoked EPSPs and their respective local voltage images shows the advantage of the high temporal resolution optical system in measuring both the spatiotemporal dynamics of segmental network excitation and integrated potentials of neuronal ensembles at identified sites.

Excitatory synaptic potentials in spastic human motoneurons have a short rise‐time

This study assessed whether changes in size or time-course of excitatory postsynaptic potentials (EPSPs) in motoneurons innervating spastic muscle could induce a greater synaptic response, and thereby contribute to reflex hyperexcitability. We compared motor unit (MU) firing patterns elicited by tendon taps applied to both spastic and contralateral (nonspastic) biceps brachii muscle in hemiparetic stroke subjects. Based on recordings of 115 MUs, significantly shortened EPSP rise times were present on the spastic side, but with no significant differences in estimated EPSP amplitude. These changes may contribute to hyperexcitable reflex responses at short latency, but the EPSP amplitude changes appear insufficient to account for global differences in reflex excitability.

Background Synaptic Conductance and Precision of EPSP-Spike Coupling at Pyramidal Cells

The temporal precision of converting excitatory postsynaptic potentials (EPSPs) into spikes at pyramidal cells is critical for the coding of information in the cortex. Several in vitro studies have shown that voltage-dependent conductances in pyramidal cells can prolong the EPSP time course resulting in an imprecise EPSP-spike coupling. We have used dynamic-clamp techniques to mimic the in vivo background synaptic conductance in cortical slices and investigated how the ongoing synaptic activity may affect the EPSP time course near threshold and the EPSP spike coupling. We report here that background synaptic conductance dramatically diminished the depolarization related prolongation of the EPSPs in pyramidal cells and improved the precision of spike timing. Furthermore, we found that background synaptic conductance can affect the interaction among action potentials in a spike train. Thus the level of ongoing synaptic activity in the cortex may regulate the capacity of pyramidal cells to process temporal information.

N- and P/Q-type Ca 2+ channels regulate synaptic efficacy between spinal dorsolateral funiculus terminals and motoneurons

Ca 2+ influx through voltage-gated Ca 2+ channels mediates synaptic transmission at numerous central synapses. However, electrophysiological and pharmacological evidence linking Ca 2+ channel activity with neurotransmitter release in the vertebrate mature spinal cord is scarce. In the current report, we investigated in a slice preparation from the adult turtle spinal cord, the effects of various Ca 2+ channel antagonists on neurotransmission at terminals from the dorsolateral funiculus synapsing motoneurons. Bath application of tetrodotoxin or NiCl 2 prevented the monosynaptic excitatory postsynaptic potentials (EPSPs), and this effect was mimicked by exposure to a zero-Ca 2+ solution. Application of polypeptide toxins that block N- and P/Q-type channels (ω-CTx-GVIA and ω-Aga-IVA) reduced the EPSP amplitude in a dose-dependent manner. By analyzing the input resistance and the EPSP time course, and using a paired pulse protocol we determined that both toxins act at presynaptic level to modulate neurotransmitter release. RT-PCR studies showed the expression of N- and P/Q-type channel mRNAs in the turtle spinal cord. Together, these results indicate that N- and P/Q-type Ca 2+ channels may play a central role in the regulation of neurotransmitter release in the adult turtle spinal cord.

Dual effect of GABA on descending monosynaptic excitatory postsynaptic potential in frog lumbar motoneurons

Monosynaptic excitatory postsynaptic potentials (EPSPs) evoked by stimulating ipsilateral ventrolateral column (VLC) in the thoracic section were recorded in lumbar motoneurons within the isolated spinal cord of the frog Rana ridibunda. Bath application of the selective GABA B receptor agonist (−)-baclofen (0.05 mM) caused a reduction in the peak amplitude of VLC EPSP. Baclofen did not cause any consistent change in the membrane potential or in the EPSP waveform within frog motoneurones. The selective GABA B receptor antagonist saclofen (0.1 mM) completely blocked the effect of (−)-baclofen on VLC EPSP. A decrease in VLC EPSP peak amplitude was also observed during GABA (0.5 mM) application. Unlike (−)-baclofen, inhibition of VLC EPSP induced by GABA was accompanied by a shortening of the EPSP time course and a reduction in membrane input resistance within lumbar motoneurons. The decrease in VLC EPSP peak amplitude induced by (−)-baclofen and GABA was accompanied by an increase in the paired-pulse facilitation. These data provide evidence for a dual pre- and postsynaptic GABAergic inhibition of the VLC monosynaptic EPSP in lumbar motoneurons within the frog spinal cord.

Genetically altered AMPA-type glutamate receptor kinetics in interneurons disrupt long-range synchrony of gamma oscillation.

Gamma oscillations synchronized between distant neuronal populations may be critical for binding together brain regions devoted to common processing tasks. Network modeling predicts that such synchrony depends in part on the fast time course of excitatory postsynaptic potentials (EPSPs) in interneurons, and that even moderate slowing of this time course will disrupt synchrony. We generated mice with slowed interneuron EPSPs by gene targeting, in which the gene encoding the 67-kDa form of glutamic acid decarboxylase (GAD67) was altered to drive expression of the alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) glutamate receptor subunit GluR-B. GluR-B is a determinant of the relatively slow EPSPs in excitatory neurons and is normally expressed at low levels in gamma-aminobutyric acid (GABA)ergic interneurons, but at high levels in the GAD-GluR-B mice. In both wild-type and GAD-GluR-B mice, tetanic stimuli evoked gamma oscillations that were indistinguishable in local field potential recordings. Remarkably, however, oscillation synchrony between spatially separated sites was severely disrupted in the mutant, in association with changes in interneuron firing patterns. The congruence between mouse and model suggests that the rapid time course of AMPA receptor-mediated EPSPs in interneurons might serve to allow gamma oscillations to synchronize over distance.

Site independence of EPSP time course is mediated by dendritic I(h) in neocortical pyramidal neurons.

Neocortical layer 5 pyramidal neurons possess long apical dendrites that receive a significant portion of the neurons excitatory synaptic input. Passive neuronal models indicate that the time course of excitatory postsynaptic potentials (EPSPs) generated in the apical dendrite will be prolonged as they propagate toward the soma. EPSP propagation may, however, be influenced by the recruitment of dendritic voltage-activated channels. Here we investigate the properties and distribution of I(h) channels in the axon, soma, and apical dendrites of neocortical layer 5 pyramidal neurons, and their effect on EPSP time course. We find a linear increase (9 pA/100 microm) in the density of dendritic I(h) channels with distance from soma. This nonuniform distribution of I(h) channels generates site independence of EPSP time course, such that the half-width at the soma of distally generated EPSPs (up to 435 microm from soma) was similar to somatically generated EPSPs. As a corollary, a normalization of temporal summation of EPSPs was observed. The site independence of somatic EPSP time course was found to collapse after pharmacological blockade of I(h) channels, revealing pronounced temporal summation of distally generated EPSPs, which could be further enhanced by TTX-sensitive sodium channels. These data indicate that an increasing density of apical dendritic I(h) channels mitigates the influence of cable filtering on somatic EPSP time course and temporal summation in neocortical layer 5 pyramidal neurons.

Amplification of EPSPs by low Ni(2+)- and amiloride-sensitive Ca2+ channels in apical dendrites of rat CA1 pyramidal neurons.

Distal synaptic input to hippocampal CA1 pyramidal neurons was evoked by electrical stimulation of afferent fibers in outer stratum radiatum. Whole cell recordings from CA1 cell somata served to monitor excitatory postsynaptic potential (EPSP) envelopes after dendritic processing. To probe a functional role of low-voltage-activated Ca2+ current [or T current I(T)] in the apical dendrite, EPSP recordings were combined with local application of antagonists of I(T). Dendritic application of low concentrations of Ni2+ (5 microM) and amiloride (50 microM) reduced EPSP amplitude measured at the soma (resting membrane potential -70 mV) by 33.0 +/- 2.9% (mean +/- SE, n = 27) and 27.0 +/- 2.1% (n = 26), respectively. No appreciable effect on EPSP time course was observed. As expected from the voltage dependence of I(T) activation, the inhibitory effect of both antagonists was strongly attenuated when EPSPs were recorded at hyperpolarized membrane potential (-90 mV). In contrast to dendritic application, somatic application of Ni2+ or amiloride produced only weak reduction of EPSP amplitude. Our data indicate that dendritic low Ni(2+)- and amiloride-sensitive Ca2+ channels giving rise predominantly to I(T) can produce substantial amplification of synaptic input. We thus propose that these channels represent an important component of subthreshold signal integration in apical dendrites of CA1 pyramidal cells.

An in vivo pharmacological study of single group Ia fibre contacts with motoneurones in the cat spinal cord.

1. Direct experimental evidence was obtained on the spatial distribution of active synaptic contacts from single Ia muscle afferents on the dendrites of lumbosacral motoneurones in anaesthetized cats. 2. An extracellular micropipette was used to pressure eject the AMPA/kainate receptor antagonists 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX) or 2,3-dihydroxy-6-nitro-7-sulphamoyl-benzo(F)quinoxaline (NBQX) in close proximity to the intracellular recording site, in order to create an extracellular concentration gradient of the antagonist. The effect of antagonist ejection on the time course and amplitude of excitatory postsynaptic potentials (EPSPs) evoked in motoneurones by impulses in single group Ia fibres was examined. 3. Pressure ejection of NBQX resulted in a complete block of the monosynaptic group Ia EPSP in two cells, and a significant reduction to 23-57% of control EPSP peak amplitudes in a further six cells (mean, 27%; n = 8). These effects were not associated with changes in membrane potential or membrane time constant. 4. The reduction in amplitude of these single group Ia fibre EPSPs following ejection of NBQX was usually accompanied by a pronounced slowing in the time course of the EPSPs. On average, the EPSP rise times and half-widths were increased by 269 and 37%, respectively. This is most probably due to a considerable spatial spread of the synaptic contacts along the dendrites of motoneurones, with the most proximal synaptic contacts (producing the briefest synaptic potentials) subjected to a greater reduction in amplitude due to a higher local antagonist concentration. 5. An equivalent dendritic cable model of the motoneurone was used to interpret the observed changes in the time course of single fibre EPSPs. The time course of control single fibre EPSPs examined in the present study could be well matched using the cable model and assuming a single location for synaptic input. The observation of a slowed EPSP time course following antagonist ejection indicated that this assumption was not correct and that there was in fact considerable spatial spread in the synaptic contacts arising from these single afferent fibres. These results provide direct evidence that spatial spread of synaptic input may not be detected using the time course of a synaptic potential in conjunction with a neuronal cable model of the postsynaptic cell.

EPSPs in rat neocortical pyramidal neurones in vitro are prolonged by NMDA receptor-mediated currents.

We investigated the influence of 2-amino-5-phosphonovalerate (APV), a selective antagonist of the N-methyl-D-aspartate (NMDA) receptor, on the time course of small excitatory postsynaptic potentials (EPSPs) in pyramidal neurones in layer 2/3 of adult rat visual cortex in vitro. Time constants of the voltage decay following the EPSPs (T(s)) and after brief (2 ms) pulses of current injected at the soma (T(p)) were determined from semilogarithmic plots of averages of 100-250 trials. The mean T(s)/T(p) ratio decreased from 1.53 +/- 0.29 (S.D.) to 1.10 +/- 0.08 on addition of 50 microM APV to the bathing medium (P less than 0.001; n = 23), but there was no significant change in EPSP peak amplitude or rise-time. These results suggest that the time course of many small EPSPs, even at negative membrane potentials and in the presence of Mg2+, can be prolonged by NMDA receptor-mediated currents.

Voltage-dependent currents prolong single-axon postsynaptic potentials in layer III pyramidal neurons in rat neocortical slices.

1. Using isolated slices of rat cingulate and sensorimotor cortex, intracellular recordings were obtained from pyramidal neurons in layer III. Simultaneous extracellular recordings were obtained from neurons in ventral layer III and layer IV. Spike-triggered averaging was employed to investigate synaptic connections from neurons in layers III/IV to pyramidal cells in layer III. 2. Of 701 simultaneously recorded pairs of neurons, comprising 699 extracellularly and 128 intracellularly recorded neurons, synaptic connections were demonstrated in 30 pairs. Of these, 29 were excitatory postsynaptic potentials (EPSPs) and 1, an inhibitory postsynaptic potential (IPSP). Single-axon EPSPs with a wide variety of amplitudes were recorded: the range recorded at membrane potentials between -68 and -72 mV was 0.079-2.3 mV. Comparing recordings obtained from different cells, EPSP amplitude was found to be independent of both the membrane resistance of the postsynaptic neuron and the EPSP time course; i.e., the largest EPSPs were not necessarily those recorded from neurons with the highest input resistance, nor those with the briefest time course. 3. Shape indices: width at half amplitude and rise-time, indicative of both proximal and distal synaptic locations were obtained. Normalized rise-times were between 0.1 and 2 times the membrane time constant and half-widths between 0.8 and 20 times. 4. The majority of postsynaptic neurons displayed nonlinear voltage relations typical of pyramidal neurons, and the contribution to EPSP shape of voltage-dependent currents was investigated. EPSP amplitude and duration were found to be dependent on membrane potential. The majority of single-axon EPSPs (26 of 29), increased in amplitude and duration with membrane depolarization over the range -95 - -50 mV, despite the significant decrease in driving force for the EPSP that would be expected to accompany such large depolarizations. This increase coincided with an increase in the amplitude of voltage responses to small injected current pulses. 5. It is concluded that the amplitude and time course of single-axon EPSPs recorded in cortical pyramidal somata are affected not only by the amplitude of the postsynaptic current and the location(s) of the synapse(s) relative to the soma, but also by voltage-dependent currents. The possibility that the increase in amplitude and duration of these EPSPs with membrane depolarization is due to N-methyl-D-aspartate receptor involvement is discussed.

Acute effects of spinal transection on EPSPs produced by single homonymous Ia-fibers in soleus alpha-motoneurons in the cat.

1. Excitatory postsynaptic potentials (EPSPs) generated in soleus motoneurons by single homonymous Ia-fibers were measured using intracellular recording and the spike-triggered averaging technique. Two groups of barbiturate-anesthetized adult cats were studied: one with the spinal cord intact and the other with the spinal cord severed at thoracic segment 13 (T13) several hours prior to recording. 2. In cord-transected cats, single homonymous Ia-fibers produced EPSPs in soleus motoneurons that were, on average, larger and faster rising relative to normal, as they are for those produced in medial gastrocnemius (MG) motoneurons (8, 12, 13, 40). Specifically, mean EPSP amplitude and rise time were, respectively, 261 +/- 22 microV and 0.65 +/- 0.05 ms for the transected group vs. 160 +/- 21 microV and 0.96 +/- 0.08 ms for the intact group. The group means for each parameter were significantly different (P less than 0.005). 3. The group difference in EPSP amplitude was largely due to a decrease in number of small EPSPs in the transected group (11% less than 100 microV compared with the normal 41%) and not due to the occurrence of unusually large ones. Ratios of the largest to smallest amplitude EPSPs produced in the same motoneuron were similarly distributed for intact and transected groups, implying that the effect of transection on EPSP size was uniform across different Ia-fiber synapses made with the same motoneuron. Mean EPSP amplitude for each transected cat (n = 5) was larger than normal, but in some cases the increase took greater than 10 h to express itself. 4. The normal tendency for EPSP rise time to decline on average with amplitude was absent in the transected group, wherein rise time was reduced to similar average values in all amplitude categories. This suggests that the decrease in rise time occurred independently of the increase in amplitude. In contrast, EPSP half-width, which tended tow ward lower than normal values [5.63 +/- 0.36 (SE) ms vs. 6.51 +/- 0.44 ms; P greater than 0.10], decreased in proportion with rise time as evidenced by the preservation of the normal relation between those parameters in transected cats. Normalizing EPSPs by motoneuron time constant (tau) reduced the group differences in rise time and half-width, suggesting that a fall in tau contributes to the abbreviation of EPSP time course. 5. The condition of the spinal cord best accounted for differences in synaptic strength between groups.(ABSTRACT TRUNCATED AT 400 WORDS)

Properties of choroid and ciliary neurons in the avian ciliary ganglion and evidence for substance P as a neurotransmitter

Intracellular recordings were made from identified choroid and ciliary neurons in the ciliary ganglion of the embryonic chick. Choroid neurons, which were innervated by multiple preganglionic fibers, frequently displayed noncholinergic slow excitatory postsynaptic potentials (EPSPs) following repetitive stimulation of the preganglionic nerve trunk. These slow potentials were blocked by high Mg2+/low Ca2+ buffer and were closely mimicked by bath application of substance P, which is known to be present within both populations of preganglionic nerve terminals. Substance P-induced depolarizations desensitized during prolonged exposure, at which time it was no longer possible to evoke slow synaptic potentials. Following manual voltage clamp to resting membrane potential, parallel increases in input resistance were seen during the slow EPSP and the response to substance P, suggesting that the two responses share common mechanisms. Ciliary neurons, which were innervated by a single preganglionic fiber and displayed dual electrical-chemical synapses, did not exhibit slow synaptic potentials and were unaffected by bath application of substance P. The magnitude and time course of fast nicotinic EPSPs elicited in ciliary neurons by 0.5 Hz presynaptic stimulation were also unchanged in the presence of 1 to 3 microM substance P. Although the ciliary and choroid neurons share a common embryological origin in the neural crest, they are specialized for quite different physiological roles. Integration of multiple presynaptic inputs occurs at choroid synapses, mediated by the presence of both subthreshold fast nicotinic EPSPs and the slow EPSP. In contrast, synapses on ciliary neurons have specializations which preclude any integrative function, including single innervation, a high quantal content, electrical coupling potentials, and a lack of slow synaptic potentials.

Influence of post-synaptic properties on the time course of synaptic potentials in different types of cat lumbar α-motoneurons

Shape indices of excitatory post-synaptic potentials (EPSPs) have been calculated on compartmental models assembled using average properties obtained from two motoneuron groups classified as fast and slow, on the basis of rheobase current and input conductance. The calculated EPSP time courses differed considerably between the two models, the rise-time and half-width being more prolonged in the slow model. With a conductance change distributed uniformly among compartments 3–6 in a 10-compartment model, the resulting shape indices in the slow and fast model, respectively, were quite similar to the apparent average values previously observed experimentally for composite Ia EPSPs in types S (slow) and F (fast) motoneurons. The results of the calculations suggest that differences in EPSP shape indices observed between F and S motoneurons arise from systematic differences in motoneuron postsynaptic properties (specific membrane resistivity and dendritic geometry) rather than differences in dendritic location of synaptic input. The results also suggest that changes in EPSP time course, following section of the motor axon, may similarly be related to changes in motorneuron postsynaptic properties.

Presynaptic inhibitory effect of acetylcholine in the hippocampus

(1) In order to investigate the effects of acetylcholine (ACh) on synaptic transmission in the rat hippocampus, extracellular and intracellular recordings were made from pyramidal neurons in an in vitro slice preparation while synaptic inputs to the cell population were stimulated. ACh was applied ionophoretically into somatic and dendritic layers of the slice. (2) ACh applied into the apical dendritic layer of the CA1 region reduced the size of the locally evoked field excitatory postsynaptic potential (EPSP) without altering the size of the afferent fiber volley. Likewise, dendritically applied ACh reduced the size of intracellularly recorded EPSPs. This effect of ACh appeared to be muscarinic since it was not affected by hexamethonium (up to 3 X 10-5 M) but was antagonized by atropine in a dose-dependent manner. (3) The distribution of Ach-sensitive sites matched closely the spatial distribution of activated synapses on the pyramidal cell dendrites as shown by ionophoretic mapping experiments. (4) In contrast to the effects of dendritic applications of ACh, ionophoresis of ACh into the cell layer resulted in an increase and prolongation of EPSPs and a transient decrease in the size of recurrent somatic inhibitory postsynaptic potentials (IPSPs). These effects on synaptic potentials could not be explained by the observed changes in membrane potential and input resistance following somatic application of ACh. (5) Short dendritic applications of ACh had no consistent effect on the membrane potential or slope conductance of pyramidal neurons and did not attenuate the depolarization evoked by brief dendritic applications of glutamate. In addition, the time course of ACh-reduced EPSPs was not different from control. (6) We conclude that ACh exerts a presynaptic inhibitory effect on both excitatory and inhibitory afferents to hippocampal pyramidal neurons. This effect of ACh is widespread, occurring in all regions of Ammon's horn tested as well as in stratum moleculare of fascia dentata.