Monosynaptic EPSPs Research Articles

Potentiation of excitatory postsynaptic potentials by a metabotropic glutamate receptor agonist (1 S,3 R-ACPD) in frog spinal motoneurons

We conducted intracellular recordings of lumbar motoneurons in the arterially-perfused frog spinal cord and investigated the effects of a metabotropic glutamate receptor agonist, (1 S,3 R)-1-aminocyclopentane-1,3-dicarboxylic acid (ACPD), on excitatory postsynaptic potentials evoked by stimulation of the descending lateral column fibers (LC-EPSPs). In the absence of Mg 2+, ACPD reversibly potentiated the amplitude of monosynaptic LC-EPSPs by more than 15% in 15 of 19 cells with 5 μM ACPD and in 7 of 12 cells with 0.5 μM ACPD. The EPSP amplitudes with 5 and 0.5 μM ACPD were 142±10% (mean±S.E.M., n=19) and 130±13% ( n=12) of the controls. The potentiation was seen without a decrease in the input conductance. Glutamate-induced depolarizations in the absence and the presence of 0.5 μM ACPD were not significantly different in cells perfused with the low Ca 2+-high Mg 2+ solution which eliminated chemical transmission. Paired pulse facilitation of LC-EPSPs was reversibly decreased in association with the potentiation. ACPD-induced potentiation of monosynaptic LC-EPSPs was seen in 5 of 6 cells in the presence of d-(−)-2-amino-5-phosphonopentanoic acid (D-AP5), an NMDA receptor antagonist. ACPD occasionally activated polysynaptic components of LC-EPSPs which were mediated mainly via NMDA receptors. On the other hand, ACPD-induced potentiation of EPSPs was inhibited by extracellular Mg 2+. Five μM ACPD potentiated monosynaptic EPSPs in 4 of 6 cells with 1 mM Mg 2+ in the solution and in 2 of 17 cells with 4 mM Mg 2+, and the EPSP amplitude was 123±9% ( n=6) and 98±3% ( n=17) of those before application of ACPD, respectively. These results suggest that activation of metabotropic glutamate receptors potentiates LC-EPSPs via mechanisms sensitive to Mg 2+ and may work as a positive feedback mechanism at the excitatory amino acid-mediated synapses between the descending fibers and lumbar spinal motoneurons.

Differences in monosynaptic EPSPs elicited by masseter and temporalis spindle afferents in anaesthetised rats.

We have used the intracellular variant of the spike triggered averaging method to examine the monosynaptic connexions of masseter and temporalis spindle afferents on jaw-elevator motoneurones. Temporalis spindle afferents elicited larger averaged EPSPs in motoneurones than masseter spindle afferents, in part because transmission at synapses of temporalis afferents was associated with lower incidences of failures. We conclude that EPSP amplitude in this motor system in governed, at least in part, by the presynaptic neurone rather than the identity of the postsynaptic neurone.

Homonymous and heteronymous monosynaptic reflexes in biceps brachii.

Using poststimulus time histograms, it has been reported that stimulation of the median nerve at the elbow produces a monosynaptic EPSP in voluntarily active single motoneurons of the human biceps brachii. The present study was undertaken to: (i) determine whether such stimulation could evoke a reproducible reflex response in biceps brachii; and (ii) establish the optimal conditions for eliciting the reflex under clinical conditions. Twelve normal subjects were studied. No reflex response was recordable when biceps brachii was relaxed. A reflex response with a mean latency of 14.0 ms (+/- 0.96 ms) could be recorded during a background voluntary contraction. The response was small (0.5-4.5% of the maximal M wave) but symmetrical, and could be obtained in all subjects. The responsible afferents appear to be rapidly conducting fibers from forearm flexor muscles and the latencies of the response were consistent with a monosynaptic reflex. Reflex amplitude increased with stimulus intensity and contraction strength. Stimulus rate did not affect amplitude significantly. It is concluded that a reproducible heteronymous monosynaptic reflex can be recorded from the contracting biceps brachii on stimulation of the median nerve at the elbow. Although smaller than the homonymous H reflex evoked by stimulation at Erb's point, it was technically easier to demonstrate that the EMG potential was of reflex origin (rather than part of an M wave). These reflexes should be of value in the assessment of the C-5/C-6 segments and the upper trunk of the brachial plexus.

Decreased monosynaptic sensory input to an identified motoneuron is associated with steroid-mediated dendritic regression during metamorphosis in Manduca sexta

The proleg withdrawal reflex of Manduca sexta larvae is mediated by mono- and polysynaptic connections from afferents innervating mechanosensory planta hairs (PHs) to ipsilateral proleg retractor motoneurons. During the larval-pupal transformation, a rise in ecdysteroids causes the dendrites of proleg motoneurons to regress and, concurrently, the proleg withdrawal reflex is lost. The objective of this study was to identify synaptic correlates of dendritic regression that contributed to this behavioral change. The accessory planta retractor (APR) motoneuron regresses during the larval-pupal transformation and dies in a segment-specific pattern after pupation. The compound excitatory postsynaptic potential (cEPSP) evoked in APR by electrically stimulating the proleg sensory nerve decreased in amplitude during the larval-pupal transformation. The developmental decrease in cEPSP amplitude, the extent of APR's regression, and several of APR's intrinsic electrical properties were similar in segments in which the motoneuron was fated to live or die. In heterochronic mosaic pupae bearing retained larval PH afferents, APR's dendritic regression was associated with decreases in both the mean amplitude of monosynaptic EPSPs produced by PH afferents and the proportion of PH afferents that produced detectable EPSPs. These changes appeared due to a developmental decrease in the size of the synaptic currents produced by PH afferents. Evidence was also obtained suggesting that PH afferents do not regress at pupation. These findings support the hypothesis that the ecdysteroid-mediated regression of proleg motoneuron dendrites disconnects them from sensory inputs and, thereby, contributes to the elimination of the proleg withdrawal reflex.

Synaptic connection patterns between frog retinal ganglion cells and tectal neurons revealed by whole-cell recordings in vivo

The synaptic connections between frog retinal ganglion cells and tectal neurons were examined by whole-cell recordings in vivo combined with nystatin perforated patch-clamp technique and pulse-triggered averaging analysis. In five tectal neurons, monosynaptic EPSPs from seven R3 retinal ganglion cells were observed. One tectal neuron was found to receive EPSPs from both R1/2 and R3 retinal ganglion cell simultaneously. Thus we could provide the first evidence for convergence of multiple types of retinal axons upon a single tectal neuron.

Facilitation of an NMDA receptor‐mediated EPSP by paired‐pulse stimulation in rat neocortex via depression of GABAergic IPSPs.

1. Tight seal, whole-cell recordings from auditory cortex in vivo and in vitro were obtained to investigate modification of N-methyl-D-aspartate (NMDA) receptor-mediated synaptic activity by paired-pulse afferent stimulation. 2. In recordings from urethane-anaesthetized rats (at 37 degrees C), or from cortical slices maintained in vitro (32 degrees C), afferent stimulation elicited a monosynaptic early EPSP and polysynaptic early and late IPSPs. In addition, a late EPSP could be elicited when the stimulus was preceded by an identical priming stimulus (interval approximately 200 ms). The late EPSP was attenuated by the NMDA receptor antagonist DL-2-amino-5-phosphonovalerate (APV, 50 microM). 3. Bath application of the gamma-aminobutyric acid-B (GABAB) receptor antagonist 3-amino-2-(4-chlorophenyl)-2-hydroxy-propylsulphonic acid (2-OH-saclofen; 50 microM) attenuated the late IPSP and clearly revealed a late EPSP. However, 2-OH-saclofen had lesser effects on the second late EPSP elicited during paired-pulse stimulation. Membrane depolarization in 2-OH-saclofen increased the magnitude of the early IPSP, which suppressed the late EPSP once again. Since pharmacological blockade of EPSPs revealed paired-pulse depression of monosynaptically elicited early and late IPSPs, these data indicate that (1) both early and late IPSPs were capable of suppressing the late EPSP, and (2) these effects were reduced during paired-pulse stimulation. 4. Pharmacological isolation of the late EPSP allowed testing of the direct effect of paired-pulse stimulation. Application of 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX, 20 microM), picrotoxin (10 microM) and 2-OH-saclofen (50 microM) isolated the late EPSP (onset, 3 ms; peak latency, 28 ms; peak amplitude, 7 mV; duration, 240 ms), which grew in magnitude with membrane depolarization and was largely (> 90%) blocked by APV. Paired-pulse stimulation depressed the isolated late EPSP by 30%. 5. Thus, apparent paired-pulse facilitation of the late EPSP is attributable to release from GABAergic inhibition, and not to direct facilitation. Facilitation of the late EPSP is a functional consequence of IPSP depression. The results indicate the importance of inhibition in regulating synaptic activity mediated by NMDA receptors.

Reduction of perineal evoked excitatory postsynaptic potentials in cat lumbar and sacral motoneurons during micturition

These experiments were undertaken to examine whether both premotoneuronal mechanisms and direct actions on motoneurons could contribute to suppression of excitatory perineal reflex pathways during micturition. Intracellular recordings were obtained from motoneurons innervating the external urethral sphincter (EUS), external anal sphincter (EAS), and selected hindlimb muscles in decerebrate male cats. The peak amplitudes of EPSPs evoked by electrical stimulation of peripheral cutaneous afferents were measured during micturition. In the EUS, EAS, and hindlimb motoneurons examined, EPSPs produced by stimulation of perineal afferents (superficial perineal or sensory pudendal nerves) were reduced in amplitude during micturition. The sample of PSPs evoked by stimulation of hindlimb cutaneous nerves recorded in hindlimb motoneurons revealed that these PSPs could also be reduced. In contrast, no changes were seen in monosynaptic EPSPs evoked by muscle afferent stimulation. The present study demonstrates that during micturition there is a strong suppression of perineal reflexes to both sphincter and hindlimb motoneurons. Since reduced EUS activity is required for efficient micturition, suppression of the strong excitatory perineal input to EUS motoneurons likely contributes to decreased EUS activity during the bladder contraction. It appears that the micturition circuitry utilizes both premotoneuronal mechanisms and direct motoneuronal inhibition to achieve this reflex suppression. The function of the micturition-related reduction of perineal reflexes to hindlimb or EAS motoneurons is not known at this time and further investigations are required to elucidate the interaction between micturition circuitry and hindlimb cutaneous pathways.

Inputs to group II-activated midlumbar interneurones from descending motor pathways in the cat.

1. Connections from descending motor pathways to group II-activated interneurones in the midlumbar segments of the spinal cord have been examined by intracellular recording. Interneurones, many of which had axonal projections to the hindlimb motor nuclei, were tested for inputs from rubro-, reticulo-, vestibulo- or corticospinal fibres. 2. Of 138 cells, 113 were monosynaptically excited by electrical stimulation of at least one of the descending motor pathways. Monosynaptic excitation from reticulo-, vestibulo- and rubrospinal pathways was common. Monosynaptic corticospinal EPSPs were identified in fewer neurones. 3. Convergent monosynaptic inputs from pathways which descend in the ventrolateral and ventral funiculi were common. Although few neurones with monosynaptic input from the corticospinal tract were identified, most also had monosynaptic rubrospinal input. In contrast, few neurones (4.3%) had convergent monosynaptic input both from pathways in the dorsolateral funiculus and from fibres in the ventral/ventrolateral funiculi. 4. The patterns of convergence from the different descending motor pathways differ from the patterns expected if the descending connections were distributed independently. Thus there is a significant segregation between rubrospinal and reticulo- or vestibulospinal inputs, and a significant association of reticulo- and vestibulospinal inputs. 5. Since descending motor pathways make monosynaptic connections with most group II-activated midlumbar neurones, many of which project to the hindlimb motor nuclei, some of these neurones provide a disynaptic pathway for the supraspinal control of hindlimb movements. The distribution of descending connections is consistent with the hypothesis that pathways descending in the dorsal part of the lateral funiculus and those descending in the ventrolateral or ventral funiculi contact different sets of interneurones.

Formation of transient inappropriate sensorimotor synapses in developing rat spinal cords

The specificity of the convergence of primary afferent projections from ankle muscles onto motoneurons that innervate these muscles was studied in lumbar spinal cords of embryonic and neonatal rats. The connectivity pattern was determined for each motoneuron by stimulating nerves from ankle flexor and extensor muscles and recording the synaptic potentials in identified motoneurons. In mature mammals, muscle spindle afferents make direct excitatory connections with motoneurons that innervate homonymous and synergistic muscles, and with interneurons that inhibit motoneurons innervating antagonistic muscles. Therefore, appropriate primary afferent-motoneuron connections were identified when stimulation of homonymous and synergistic muscle nerves evoked monosynaptic EPSPs. Two criteria were used for identification of EPSPs as monosynaptic potentials: (1) the monosynaptic potentials were evoked at the shortest latency, and (2) they were more resistant to fatigue by repetitive nerve stimulation than the longer-latency, polysynaptic potentials. Functionally inappropriate primary afferent-motoneuron contacts were identified when stimulation of an antagonistic muscle nerve produced monosynaptic EPSPs instead of polysynaptic IPSPs in homonymous motoneurons. At days 18-21 of gestation, about 30% of motoneurons were innervated by primary afferents of antagonist muscles. Such functionally inappropriate synapses persisted at birth, but their percentage was significantly reduced within 3-5 d after birth. The findings suggested that in the developing spinal cord of the rat, a significant percentage of motoneurons were initially innervated by inappropriate primary afferents of antagonistic muscles. The decrease in percentage of such inappropriate connections was correlated temporally with the increase in the frequency of spontaneous activity and the onset of myelination.

A presynaptic gain control mechanism among sensory neurons of a locust leg proprioceptor

The chordotonal organ at the femorotibial joint of a locust hind leg monitors extension and flexion movements of the tibia. During evoked or imposed movements of this joint the central terminals of afferent neurons from the chordotonal organ receive depolarizing, inhibitory synaptic inputs. The afferent spikes are therefore superimposed on these depolarizing IPSPs, which are generated indirectly by other afferents from the same organ that respond to the same movement. Each afferent spikes preferentially to particular features of a joint movement, and its synaptic input is typically greatest at the joint position or during the movement that generates its best response. Afferents that respond to only one direction of movement receive synaptic inputs either during movements in both directions, or only during movements in their preferred direction. Phasic velocity-sensitive afferents receive either phasic inputs during movements, or tonic inputs at new sustained joint positions, or both. The spikes of tonic position-sensitive afferents are superimposed on synaptic inputs that are dependent on joint position. The synaptic inputs sum but do not themselves evoke antidromic spikes in the afferent terminals. They reduce the amplitude of orthodromic afferent spikes by 12-28%, and this is accompanied by a reduction of up to 50% in the amplitude of monosynaptic EPSPs evoked by an afferent in postsynaptic leg motor neurons. These interactions suggest that a local gain control mechanism operates between the afferents of this proprioceptor. Thus, the effectiveness of the output synapses of an individual afferent is regulated by the network action of other chordotonal afferents that respond to the same movement.

Effects of Mg 2+ on ACPD-induced enhancement of monosynaptic EPSPs in spinal motoneurons

Effects of Mg 2+ on ACPD-induced enhancement of monosynaptic EPSPs in spinal motoneurons

Patterns of monosynaptic input to the giant interneurons 1?3 in the cereal system of the adult cockroach

1. The cerci of the cockroach Periplaneta americana bear filiform hair mechanoreceptors that are arranged in segmentally repeated rows and longitudinal columns. The monosynaptic connections between receptors of the same column or row and the 3 largest giant interneurons (GIs) were compared using the oil-gap single fibre technique. 2. For many columns, the synaptic efficacy of the afferents decreased gradually from the base to the tip of the cercus, but columns with an inverted gradient or without any gradient were also observed. On the ipsilateral side (relative to the GI axon), the inverted gradients were exclusively found for columns with short proximal hairs. For one column (d) and GI3, the ipsilateral and contralateral gradients were opposite. 3. Monosynaptic EPSPs evoked by stimulating different receptors of the same segment (segment 3) were of very different amplitudes, which partially account for the directional sensitivity of the GIs. Differences in the location, shape and size of the afferent terminals were not sufficient to explain these differences in connection strength. 4. No correlation was found between the size of the EPSPs produced by a sensory neuron and the length of its associated hair.

Long-term potentiation and long-term depression of primary afferent neurotransmission in the rat spinal cord

Synaptic transmission between dorsal root afferents and neurons in the superficial laminae of the spinal dorsal horn (laminae I-III) was examined by intracellular recording in a transverse slice preparation of rat spinal cord. Brief high-frequency electrical stimulation (300 pulses at 100 Hz) of primary afferent fibers produced a long-term potentiation (LTP) or a long-term depression (LTD) of fast (monosynaptic and polysynaptic) EPSPs in a high proportion of dorsal horn neurons. Both the AMPA and the NMDA receptor-mediated components of synaptic transmission at the primary afferent synapses with neurons in the dorsal horn can exhibit LTP and LTD of the synaptic responses. In normal and neonatally capsaicin-treated rats, the induction of LTP requires the activation of NMDA receptor-gated conductances. The induction of LTP or LTD, however, was not abolished in the presence of bicuculline, a GABAA receptor antagonist. The results demonstrate that distinct and long-lasting modulation in synaptic efficiency can be induced at primary afferent synapses with neurons in the superficial laminae of spinal dorsal horn by high-frequency stimulation of dorsal root afferents and that these changes may be physiologically relevant for transmission and integration of sensory information, including pain.

Role of synaptic excitation in the generation of bursting-induced epileptiform potentials in the endopiriform nucleus and piriform cortex

1. The mechanism of generation of epileptiform excitatory postsynaptic potentials (e-EPSPs) induced by bursting activity in vitro was examined in slices of piriform cortex. 2. Previous study revealed that e-EPSPs in piriform cortex are generated in the subjacent endopiriform nucleus, perhaps with a contribution from the claustrum and deep part of layer III of piriform cortex. A puzzling feature of these e-EPSPs was their abrupt origin at long latency with little sign of preceding abnormal activity. 3. Systematic mapping revealed that within spatially restricted regions of the endopiriform nucleus there is an irregular buildup in extracellularly recorded multiunit activity and intracellularly recorded depolarization that precedes the onset of e-EPSPs. Analysis of latency revealed that these "slow-onset" e-EPSPs precede the more widely distributed "abrupt-onset" e-EPSPs, suggesting that they occur at sites of initiation. 4. The hypothesis was tested that the buildup associated with slow-onset e-EPSPs is dependent on synaptically mediated excitation. According to this hypothesis, all-or-none e-EPSPs originate when mutually excitatory (positive feedback) interactions within a population of cells in the endopiriform nucleus become self-regenerative. 5. Predictions from the regenerative positive feedback hypothesis that were successfully verified include the presence of excitatory synaptic connections between cells in the endopiriform nucleus; the consistent prediction of a subsequent e-EPSP from the occurrence of the accelerating buildup in population activity; the occurrence of inhibitory postsynaptic potentials (IPSPs) together with EPSPs during the buildup period; and the blockage of the buildup and e-EPSP by a low concentration of a specific excitatory amino acid antagonist 6,7-dinitroquinoxaline-2,3-dione (DNQX). 6. Blockage of e-EPSPs by a concentration of DNQX that was much less than that required to block monosynaptic EPSPs in the endopiriform nucleus indicates that synaptic reverberation is mediated by alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA) type excitatory amino acid receptors. 7. D-2-amino-5-phosphonovaleric acid (D-APV) reduced the duration and amplitude of e-EPSPs but did not block their occurrence, indicating that N-methyl-D-aspartate (NMDA) receptors have a boosting effect on e-EPSPs but are not required for their generation. This is in contrast to the induction of e-EPSPs by bursting activity for which NMDA receptor activation is required. 8. Outside the region of initiation e-EPSPs propagated through the endopiriform nucleus at a velocity of 0.1 m/s.(ABSTRACT TRUNCATED AT 400 WORDS)

Pattern of monosynaptic heteronymous Ia connections in the human lower limb.

Changes in the firing probability of single motor units in response to electrical stimulation of muscle nerves were used to derive the projections of muscle spindle Ia afferents to the motoneurones of various leg and thigh muscles. Discharges of units in soleus, gastrocnemius medialis, peroneus brevis, tibialis anterior, quadriceps, biceps femoris and semitendinosus were investigated after stimulation of inferior soleus, gastrocnemius medialis, superficial peroneal, deep peroneal and femoral nerves. Homonymous facilitation, occurring at the same latency as the H reflex and therefore attributed to monosynaptic Ia EPSPs, was found in virtually all the sampled units. In many motor nuclei an early facilitation was also evoked by heteronymous low-threshold afferents. The heteronymous facilitation was considered to be mediated through a monosynaptic pathway when the difference between the central latencies of heteronymous and homonymous peaks was not more than 0.2 ms. The heteronymous Ia connections were widely distributed. In particular, monosynaptic coupling between muscles operating at different joints appears to be the rule in humans, though it is rare between ankle and knee muscles in the cat and the baboon.

The regulation of presynaptic inhibition during co-contraction of antagonistic muscles in man.

1. The size of the soleus, tibialis anterior and medial gastrocnemius H reflexes were measured at different levels of EMG activity in ankle plantar- and dorsiflexors. At similar levels of EMG activity in the agonist muscle, the soleus and tibials anterior H reflexes were found to be smaller during co-contraction than during an isolated agonist contraction. In contrast to this, the medial gastrocnemius H reflex had the same size during co-contraction as during an isolated plantarflexion at comparable EMG levels. 2. Peaks occurred at monosynaptic reflex latency in the post-stimulus time histogram (PSTH) of firing of soleus and tibialis anterior motor units following stimulation of their respective motor nerves. These homonymous Ia peaks were found to be smaller during co-contraction than during isolated agonist contraction, whereas that of medial gastrocnemius motor units was unchanged. As the monosynaptic peak in the PSTH may give an indirect measure of the size of the monosynaptic EPSP in the motoneurone, it is suggested that these findings reflect a differential control of presynaptic inhibition of soleus and tibialis anterior motor units with respect to medial gastrocnemius motor units. 3. The monosynaptic Ia facilitation of the soleus H reflex evoked by a stimulation of the femoral nerve, was also found to be smaller during co-contraction of tibials anterior and soleus than during isolated plantarflexion. This suggests that presynaptic inhibition of heteronymous Ia fibres from the quadriceps muscle projecting to soleus motoneurones is regulated in the same way as presynaptic inhibition of homonymous Ia fibres during co-contraction. 4. The femoral nerve-induced monosynaptic facilitation of the soleus H reflex was found to decrease with increasing tonic levels of both co-contraction and isolated dorsi- and plantarflexion. The amount of facilitation decreased to the same degree with increasing levels of dorsiflexion and co-contraction. For the same level of EMG in the dorsiflexors there was thus no difference in the amount of facilitation whether the dorsiflexors were activated separately or in a co-contraction. 5. Whereas the soleus H reflex increased in size 50 ms prior to the onset of a dynamic plantarflexion, it did not change prior to the onset of a co-contraction. The femoral nerve-induced facilitation increased prior to the plantarflexion, but decreased prior to the co-contraction.(ABSTRACT TRUNCATED AT 400 WORDS)

Organization of Excitatory Inputs from the Cerebral Cortex to the Cerebellar Dentate Nucleus

Intracellular recording was made from dentate nucleus neurons (DNNs) in anesthetized cats, to investigate cerebral inputs to DNNs and their responsible pathways. Stimulation of the medial portion of the contralateral pericruciate cortex most effectively produced EPSPs followed by long-lasting IPSPs in DNNs. Stimulation of the pontine nucleus (PN), the nucleus reticularis tegmenti pontis (NRTP) and the inferior olive (IO) produced monosynaptic EPSPs and polysynaptic IPSPs in DNNs. The results indicate that the excitatory input from the cerebral cortex to DNNs is at least partly relayed via the PN, the NRTP and the IO. Intraaxonal injection of HRP visualized the morphology of mossy fibers from the PN to the DN and the cerebellar cortex. The functional significance of the excitatory inputs from the PN and the NRTP to the DN is discussed in relation to the motor control mechanisms of the cerebellum.

Bag cell extract inhibits tail-siphon withdrawal reflex, suppresses long-term but not short-term sensitization, and attenuates sensory-to- motor neuron synapses in Aplysia

The peptides released from the bag cells (bag cell peptides, BCPs) in Aplysia californica are responsible for eliciting or modulating a repertoire of behaviors preceding and accompanying egg laying. Our interest was in determining to what extent behaviors that can occur simultaneously with egg laying are modulated. To address this issue, we examined the effects of an extract (bag cell extract, BCE) that contained BCPs, as well as egg-laying hormone (ELH), an identified BCP, on both the tail-siphon withdrawal reflex and the ability of that reflex to exhibit sensitization, a simple form of nonassociative learning. In addition, we examined the ability of BCE, as well as the individual BCPs, to modulate a component of the circuitry of the reflex. Behavioral experiments indicated that BCE inhibited the baseline withdrawal reflex and suppressed long-term sensitization of the reflex while leaving short-term sensitization unaffected. These effects were not observed in animals receiving an extract of a control ganglion or in animals receiving ELH, and therefore may be attributed to the actions of one or more BCPs, but presumably not to ELH alone. Electrophysiological experiments revealed that BCE also attenuated the monosynaptic EPSP elicited in tail motor neurons by tail sensory neurons. In subsequent experiments in which the BCPs were individually applied, only one BCP, beta-BCP, significantly attenuated the EPSPs. This effect was independent of narrowing of the presynaptic action potential. Taken together, these results suggest a novel behavioral modification attributed to BCPs, inhibition of the tail-siphon withdrawal reflex, and suggest a possible locus of action and peptide candidate for this effect. In addition, these experiments raise the possibility that BCPs may exert a long-lasting effect (> 24 hr), selectively blocking a simple form of long-term memory.

Long-term changes in synaptic strength along specific intrinsic pathways in the cat visual cortex.

1. The dense system of horizontal connections that arise and course within the striate cortex are thought to inform single cells about stimuli arising in disparate points in visual space and to modulate responses evoked from within the receptive field. To learn whether or not the strength of the horizontal connections could vary over the long term, and if such changes could affect the integration of vertical, interlaminar inputs, we have recorded intracellularly from the superficial layers in slices of the adult cat's visual cortex. 2. The monosynaptic EPSP evoked by stimulating horizontal fibres showed long-term facilitation in twelve of the twenty cells that were conditioned by repetitively pairing synaptic responses with depolarizing pulses of current; the maximum increase observed was 200%. Strong inhibition present in the postsynaptic response usually indicated that facilitation would not occur. 3. In instances where horizontal input evoked both mono- and polysynaptic EPSPs, both early and late events showed facilitation, with the most dramatic enhancement contributed by the polysynaptic components. 4. For the twenty-eight cells whose responses to stimulation of interlaminar as well as horizontal pathways were assessed, all were found to receive non-overlapping inputs from each source. Conditioning produced long-term changes in the strength of the interlaminar inputs. 5. Changes in synaptic strength were usually confined to the conditioned pathway, though in four out of twenty-six times we observed heterosynaptic facilitation of polysynaptic EPSPs. 6. The conditioning protocol led to lasting depression rather than facilitation in three out of eleven instances; the reduction was only observed in the multisynaptic components. 7. We suggest that the synaptic changes observed here may be related to certain dynamic changes in receptive field properties that have been characterized in vivo.

Electrophysiological responses in foetal spinal cord transplants evoked by regenerated dorsal root axons.

Cut dorsal root axons regenerate into intraspinal transplants of foetal spinal cord (FSC) and establish synaptic connections there. The aim of the present study was to determine whether transplant neurons are driven synaptically in response to electrical stimulation of regenerated dorsal root axons. Adult Sprague-Dawley rats received FSC transplants (E14) into dorsal quadrant cavities at the lumbar enlargement. The cut L4 or L5 dorsal root stump was placed at the bottom of the lesion cavity and secured between the transplant and host spinal cord. Four to ten weeks later the animals were prepared for electrical stimulation and recording. We stimulated regenerated dorsal roots and recorded extracellular single unit post-synaptic activities which were evoked close to the dorsal root-transplant interface. We used intracellular recording to observe several examples of monosynaptic EPSPs in transplant neurons evoked by dorsal root stimulation. These results indicate that the regenerated dorsal root axons establish functional connections with neurons within the transplants and suggest that FSC transplants can be used to reconstruct functional connections between neurons that have been interrupted by spinal cord injury.