Monosynaptic excitation of dorsal medullary respiratory neurons by slowly adapting pulmonary stretch receptors

The discharges of individual slowly adapting pulmonary stretch receptors (PSRs) and single respiratory neurons of the dorsal respiratory group (DRG) within the ventrolateral subnucleus of the solitary tract were recorded simultaneously in anesthetized, paralyzed, artificially ventilated cats. DRG neurons were classified as P-cell, I-alpha, or I-beta, based on the alteration in activity during respiratory cycles when lung inflation was withheld compared to activity when the lungs were inflated in phase with central inspiratory drive. In some cases, vagal stimulation was also used to classify respiratory neurons. Synaptic input of PSRs onto DRG neurons was examined by the construction of cross-correlograms for the simultaneously recorded discharge of individual PSRs (reference events) and individual DRG neurons (correlated events). Monosynaptic excitatory connections were demonstrated by peaks in 26% of the cross-correlograms of PSR and P-cell pairs and 20% of the cross-correlograms of PSR and I-beta neuron pairs. The ratio of the peak number of occurrences to the background number of occurrences (k value) was comparable for P-cells and I-beta neurons: 2.96 +/- 2.09 and 1.62 +/- 0.36 (mean +/- SD), respectively. P-cells and I-beta neurons also had similar short latencies for the peak of increased probability of discharge: 2.74 +/- 0.53 and 2.57 +/- 0.63 ms, respectively. No evidence was obtained demonstrating synaptic connectivity between PSRs and I-alpha neurons. Interpretations of this negative result are discussed.     

Modulation of synaptic effectiveness of Ia and descending fibers in cat spinal cord.

1. In the unanesthetized spinal cord, conditioning stimulation of low-threshold afferents (below 1.3 times threshold strength) in the biceps semitendinosus (BST) nerve often reduced the peak amplitude of the monosynaptic Ia EPSPs evoked in gastrocnemius motoneurons without affecting the monosynaptic component of the EPSPs evoked by stimulation of the ipsilateral ventral funiculus (VF) in the thoracic cord. 2. Volleys to the BST nerve comprising higher threshold afferents (usually above 1.4 times threshold strength) reduced the peak amplitude of the monosynaptic Ia and VF EPSPs and shortened their falling phase. 3. Conditioning volleys to low-threshold cutaneous afferents often increased the Ia-EPSP peak amplitude, sometimes without affecting the monosynaptic component of the VF EPSP. 4. In most cases the Ia nd VF monosynaptic EPSPs elicited in a given motoneuron summated nonlinearly. The amount of nonlinear summation between Ia and VF monosynaptic EPSPs was often reduced by low-threshold BST conditioning volleys. These observations suggest that in many instances, both species of fibers end in "electrotonically close" synaptic loci over the motoneuron surface. Therefore, amplitude changes of monosynaptic Ia EPSPs produced by conditioning afferent volleys without concomitant changes of monosynaptic VF EPSPs do not appear to result from postsynaptic remote conductance changes and may be attributed to a presynaptic mechanism. 5. At the time of occurrence of the Ia and VF monosynaptic EPSP the variance of the motoneuron membrane potential may be increased above base-line levels with a time course approximately matching the EPSP itself. Conditioning stimulation of BST afferents usually reduced Ia EPSP variance, often without affecting or even increasing the variance of the monosynaptic VF EPSPs. These observations provide additional evidence that Ia EPSP variability is introduced, at least in part, through the segmental pathways mediating primary afferent depolarization. 6. The possibility of a differential control of the information flow transmitted through two independent channels converging on a given cell ensemble is discussed.     

Effects on the ventral spinocerebellar tract neurones from deiters' nucleus and the medial longitudinal fascicle in the cat.

Effects from the vestibulospinal tract (VST) and from fibres descending in the medial longitudinal fascicle (MLF) on the cells of origin of the ventral spinocerebellar tract (VSCT) have been studied with intracellular recording. Out of 110 VSCT neurones, the VST evoked monosynaptic EPSPs in 27, di- or polysynaptic EPSPs in 56 and disynaptic IPSPs in 26. In 93 tested VSCT cells, MLF stimulation evoked monosynaptic EPSPs in 26, monosynaptic IPSPs in 2, di- or polysynaptic EPSPs in 25 and disynaptic IPSPs in 21. Convergence of monosynaptic EPSPs from VST and MLF was found in a small proportion of cells whereas the two descending pathways evoked reciprocal effects in another small group of neurones. Convergence of monosynaptic EPSPs from VST or MLF and from group I afferents was also modest. In 9 VSCT neurones there was convergence of monosynaptic excitation and disynaptic inhibition from the vestibulospinal tract and the same pattern from MLF was recorded in 9 neurones. The results are discussed in view of the hypothesis that VSCT neurones carry information on the interneuronal ttransmission in the spinal cord.     

Monosynaptic connexions of low threshold muscle afferents with hindlimb motoneurones in the turtle spinal cord

Summary Excitatory postsynaptic potentials (EPSPs) were recorded intracellularly from hindlimb motoneurones of the anaesthetized fresh water turtle. The EPSPs were evoked from low threshold muscle afferents and the amplitudes saturated for stimuli less than two times the nerve threshold. The segmental latencies of these EPSPs, measured from the initial positive peak of the triphasic cord dorsum potential to the onset of the EPSP, ranged from 1.5 to 3.1 ms. The intraspinal conduction time of afferents was estimated by recording afferent volleys in the grey matter along the vertical course of intraspinal afferent fibres. The synaptic delay was estimated by subtracting the latency of the afferent volley at the deepest region of the dorsal horn from the segmental latency of the EPSP (in the range from 1.6 to 2.1 ms) recorded in the same microelectrode track. The average value was 0.99 ms (range: 0.9–1.1 ms), which was close to the known synaptic delay of cold-blooded animals. Therefore, the EPSPs in this range of segmental latencies were regarded as monosynaptic. Taking account of the intraspinal afferent conduction time (0.8 ms on average) and another synaptic delay, the latency for disynaptic transmission would be 2.8 ms or more. Thus, EPSPs having segmental latencies of 1.5–3.1 ms were suggested to be almost all monosynaptic in nature, at least under the present conditions of deep anaesthesia. On the basis of the above criteria for the monosynaptic nature of EPSPs, the pattern of convergence of monosynaptic excitatory inputs from various muscle afferents was investigated. Monosynaptic EPSPs were induced from the homonymous muscle nerve and the nerve innervating the synergist at the same joint. The heteronymous EPSPs were also found between muscles within each group of the anterodorsal musculature and the posteroventral musculature. No monosynaptic connexions were found between anterodorsal and posteroventral muscles except between the muscles innervated by the peroneal and the tibial nerve.     

Rubrospinal effects on ventral spinocerebellar tract neurones.

Stimulation of the contralateral red nucleus evoked monosynaptic EPSPs in 14 of 82 ventral spinocerebellar tract neurones. In some of these cells the monosynaptic EPSP was followed by a disynaptic IPSP. The remaining cell population received di- or polysynaptic PSPs from the rubrospinal tract, either EPSPs or IPSPs or both. Convergence of the rubrospinal tract onto interneurones of the segmental pathways projecting to VSCT cells was demonstrated. Rubrospinal volleys facilitated disynaptic Ia IPSPs evoked in VSCT neurones from both flexors and extensors, as well as disynaptic Ib IPSPs. Facilitation of the Ia interneurones was disynaptic whereas facilitation of Ib interneurones was monosynaptic. Disynaptic rubrospinal EPSPs and IPSPs were facilitated by volleys in ipsi- as well as in contralateral cutaneous and high threshold muscle afferents. The complex pattern of projections from the rubrospinal tract onto VSCT neurones and the related reflex pathways gives further support to the hypothesis that these tract cells convey information on transmission through interneurones of the spinal segmental mechanisms.     

Rubrospinal Effects on Ventral Spinocerebellar Tract Neurones

Stimulation of the contralateral red nucleus evoked monosynaptic EPSPs in 14 of 82 ventral spinocerebellar tract neurones. In some of these cells the monosynaptic EPSP was followed by a disynaptic IPSP. The remaining cell population received di- or polysynaptic PSPs from the rubrospinal tract, either EPSPs or IPSPs or both. Convergence of the rubrospinal tract onto interneurones of the segmental pathways projecting to VSCT cells was demonstrated. Rubrospinal volleys facilitated disynaptic Ia IPSPs evoked in VSCT neurones from both flexors and extensors, as well as disynaptic Ib IPSPs. Facilitation of the Ia interneurones was disynaptic whereas facilitation of Ib interneurones was monosynaptic. Disynaptic rubrospinal EPSPs and IPSPs were facilitated by volleys in ipsi- as well as in contralateral cutaneous and high threshold muscle afferents. The complex pattern of projections from the rubrospinal tract onto VSCT neurones and the related reflex pathways gives further support to the hypothesis that these tract cells convey information on transmission through interneurones of the spinal segmental mechanisms.     

Primary afferents evoke excitatory amino acid receptor-mediated EPSPs that are modulated by presynaptic GABAB receptors in lamprey.

1. The primary afferent neurons (dorsal cells) are of two types in lamprey, which are fast (touch) and slowly adapting (pressure), respectively. Intracellular stimulation of such sensory neurons evokes mono- and polysynaptic excitatory postsynaptic potentials (EPSPs) in spinobulbar neurons (giant interneurons) and in unidentified interneurons. Paired intracellular recordings between identified sensory cells and spinobulbar neurons made it possible to study the synaptic transmission in detail. It is shown that both touch and pressure primary afferents utilize excitatory amino acid (EAA) transmission and, furthermore, that these effects are subject to a presynaptic GABAB receptor modulation. 2. The monosynaptic mixed electrical and chemical EPSPs in giant interneurons had a mean peak amplitude of 3.2 +/- 1.3 (SD) mV, a time to peak of 4.7 +/- 1.2 ms, and a duration at one-half peak amplitude of 9.4 +/- 3.2 ms. Corresponding results were obtained with dorsal root or dorsal column stimulation. Seventy percent of the fast-adapting dorsal cells of the "touch" type evoked monosynaptic mixed EPSPs in giant interneurons, whereas only 3% of the slowly adapting "pressure" dorsal cells did. 3. The chemical part of the monosynaptic EPSPs evoked in giant interneurons was, in all cases tested, blocked by application of EAA antagonists, like the nonselective antagonist kynurenic acid (KYAC; 2 mM). The selective kainate/alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor antagonist 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX; 5 microM) had a similar effect, whereas the selective N-methyl-D-aspartate (NMDA) receptor antagonist 2-aminophosphono-5-valeric acid (AP-5; 200-400 microM) did not change the EPSP, even in the absence of magnesium ions. 4. The monosynaptic excitatory synaptic transmission was modulated by application of the selective GABAB receptor agonist L-baclofen (5-10 mM local droplet application or 100-1,000 microM bath applied) or by gamma-aminobutyric acid (GABA; 100-1,000 microM), also when GABAA receptor-evoked effects were blocked by bicuculline (10 microM). L-baclofen or GABA in combination with bicuculline did not evoke any effects in the postsynaptic neuron on membrane potential, input resistance, or spike threshold. Therefore the effects of the GABAB receptor activation most likely occurs at the presynaptic afferent level. 5. In conclusion, the monosynaptic excitation from skin mechanoreceptors evoked in spinobulbar neurons is mediated by EAA receptors of the kainate/AMPA type. GABAB receptor activation causes a depression of this EPSP, most likely because of a presynaptic action. GABA interneurons are known to form close appositions on sensory axons in the lamprey.     

Excitation and inhibition of medullary inspiratory neurons by two types of burst inspiratory neurons in the cat

In Nembutal-anesthetized and artificially ventilated cats, we studied the connectivity of burst inspiratory (I) neurons in the B?tzinger complex and the ventral respiratory group (VRG) with spike-triggered averaging methods. Burst I neurons exhibited tonic (I-TON) or decrementing (I-DEC) firing patterns. Spikes of I-TON neurons induced monosynaptic EPSPs in intracellularly recorded I neurons of both the VRG and the dorsal respiratory group (DRG). Spikes of I-DEC neurons induced monosynaptic inhibitory postsynaptic potentials (IPSPs) in both VRG and DRG I neurons.     

Arrhythmic firing in dopamine neurons of rat substantia nigra evoked by activation of subthalamic neurons.

Intracellular recordings were made from dopaminergic neurons of the rat substantia nigra compacta (SNc) in in vitro slice preparations to study the synaptic influence from the subthalamic nucleus (STh). After microstimulation of STh, monosynaptic excitatory postsynaptic potentials (EPSPs) were produced in dopaminergic neurons. STh-induced EPSPs were composed of 6-cyano-7-nitroquinoxalene-2,3-dione- and 2-amino-5-phosphonovaleric acid-sensitive components. Subthreshold EPSPs evoked by STh stimulation could differentially trigger pacemaker-like slow depolarization (PLSD) and low-threshold Ca2+ spike (LTS) depending on the level of baseline membrane potentials. When a subthreshold EPSP was evoked by STh stimulation during rhythmic firing, the STh-induced EPSP could shift or elevate PLSD to a more depolarized level, resulting in generation of a spike at an earlier arrhythmic timing to restart the rhythmic firing. The interspike interval after the arrhythmic spike remained almost unchanged. In contrast, when a suprathreshold EPSP for evoking spikes was produced by STh stimulation during rhythmic firing, the STh-induced spike was just interposed between two spontaneous spikes the interspike interval of which was almost the same as those seen during the preceding rhythmic firing. This ectopically induced spike did not disturb or reset rhythmic firing. It was concluded that SNc dopaminergic neurons receive monosynaptic glutamatergic inputs from STh, and subthreshold and suprathreshold EPSPs evoked by STh stimulations can induce two types of arrhythmic firing in SNc dopaminergic neurons, similar to arrhythmic occurrences of the QRS complex seen in the electrocardiogram of the atrial and ventricular arrhythmias, respectively. The former arrhythmic firing may play a crucial role in desynchronization of dopaminergic neurons.     

Cortically evoked pre-and postsynaptic inhibition of impulse transmission to the dorsal spinocerebellar tract

Summary Synaptic actions evoked from primary afferents and the sensorimotor cortex in neurones of the dorsal spinocerebellar tract were investigated: 1. Stimulation of the anterior lobe of the cerebellum produced a small IPSP in only one but not in the other six neurones examined. 2. IPSPs were induced not only from group I fibres (in 41% of group I neurones) but also from cutaneous and/or high threshold muscle afferents (in 37%). 3. Stimulation of the contralateral sensorimotor cortex evoked IPSPs in 80% of group I neurones. The IPSP had a latency of 10–15 msec and lasted for 40–100 msec. EPSPs were evoked from the cortex in a small number of neurones. 4. Effects from the cortex were compared with those from primary afferents in individual neurones. The cortical IPSPs were induced independently of whether the neurone received monosynaptic EPSP from extensor or flexor group I fibres. The cortical IPSPs (or EPSPs) occurred more frequently in neurones which exhibited polysynaptic IPSPs (or EPSPs) from primary afferents. 5. The few FRA neurones encountered were all excited from the cortex.Excitability measurements of primary afferent terminals in or near Clarke's column showed that a terminal depolarization is evoked from the cortex in group Ib but not in Ia afferents.The relative importance of post-and presynaptic inhibition of transmission to the DSCT is discussed.     

Synaptic organization in teleost spinal motoneurons.

Glass microelectrodes were inserted into motoneurons innervating pectoral fin muscles to record action and synaptic potentials, evoked by electrical stimulation of ventral and dorsal roots, and the medulla oblongata. Ventral root stimulation evoked a small depolarizing response which had properties compatible with those of the EPSP; its amplitude changes were graded, being increased by membrane hyperpolarization and decreased by high frequency repetitive stimulation. The latency of the response was sufficiently longer than that of the antidromic spike to allow for a monosynaptic delay. Stimulation of the dorsal root produced EPSPs with relatively long latencies, suggesting mediation by a polysynaptic pathway. EPSPs with short latencies were evoked by stimulation of the medulla oblongata, indicating the presence of a monosynaptic excitatory connection. Action potentials, recorded from peripheral nerve after stimulation of the medulla oblongata, were facilitated by conditioning volleys via ventral roots. This facilitation was blocked by dihydro-beta-erythroidine hydrobromide and atropine sulphate, indicating the cholinergic nature of the EPSP of ventral root origin. The conduction velocities of motor axons and of the ventral roots fibers responsible for production of EPSPs were about the same. The EPSP of ventral root origin had a slower rising time course and lesser sensitivity to shifts of membrane potential than the EPSP of medulla oblongata origin, suggesting that the sites of generation of the former EPSP were on the peripheral dendrites. From the above results, it was concluded that the EPSP of ventral root origin was mediated by recurrent axon collaterals of motoneurons.     

Effects on the Ventral Spinocerebellar Tract Neurones from Deiters' Nucleus and the Medial Longitudinal Fascicle in the Cat

Effects from the vestibulospinal tract (VST) and from fibres descending in the medial longitudinal fascicle (MLF) on the cells of origin of the ventral spinocerebellar tract (VSCT) have been studied with intracellular recording. Out of 110 VSCT neurones, the VST evoked monosynaptic EPSPs in 27, di- or polysynaptic EPSPs in 56 and disynaptic lPSPs in 26. In 93 tested VSCT cells, MLF stimulation evoked monosynaptic EPSPs in 26, monosynaptic IPSPs in 2, di- or polysynaptic EPSPs in 25 and disynaptic IPSPs in 21, Convergence of monosynaptic EPSPs from VST and MLF was found in a small proportion of cells whereas the two descending pathways evoked reciprocal effects in another small group of neurones. Convergence of monosynaptic EPSPs from VST or MLF and from group 1 afferents was also modest. In 9 VSCT neurones there was convergence of monosynaptic excitation and disynaptic inhibition from the vestibulospinal tract and the same pattern from MLF was recorded in 9 neurones. The results are discussed in view of the hypothesis that VSCT neurones carry information on the interneuronal transmission in the spinal cord.     

Synaptic input from homonymous group I afferents in m. longissimus lumborum motoneurons in the L4 spinal segment in cats

We examined the relationship between input resistance and amplitude of monosynaptic and polysynaptic EPSPs produced by electrical stimulation of group I muscle afferents innervating the m. longissimus lumborum (Long) at different levels (L1–L4) in Long motoneurons in L4 spinal segments to obtain an insight into the neuronal control of trunk muscles. In the Long motoneuron pool, the amplitude of monosynaptic EPSP was shown to have a close relationship to input resistance. Furthermore, the relation between the amplitude of polysynaptic EPSP after stimulating Long nerves at L3 and input resistance was statistically significant, but the relation between EPSP amplitude evoked by stimulation of Long at L1 or L2 and input resistance was not statistically significant. Our findings suggest a position-dependent control of motoneuron activity by group I muscle afferents. The motoneuron activities carried out by monosynaptic pathways and polysynaptic pathways from adjacent spinal segments are dependent on the intrinsic properties of motoneurons (input resistance, etc.), while the motoneuron activities carried out by polysynaptic pathways from the far spinal segments have independent intrinsic properties.     

Interaction between peripheral afferent activity and presynaptic inhibition of ia afferents in the cat

It has been demonstrated in man that the H-reflex is more depressed by presynaptic inhibition than the stretch reflex. Here we investigated this finding further in the alpha-chloralose-anesthetized cat. Soleus monosynaptic reflexes were evoked by electrical stimulation of the tibial nerve or by stretch of the triceps surae muscle. Conditioning stimulation of the posterior biceps and semitendinosus nerve (PBSt) produced a significantly stronger depression of the electrically than the mechanically evoked reflexes. The depression of the reflexes has been shown to be caused by presynaptic inhibition of triceps surae Ia afferents. We investigated the hypothesis that repetitive activation of peripheral afferents may reduce their sensitivity to presynaptic inhibition. In triceps surae motoneurones, we measured the effect of presynaptic inhibition on excitatory postsynaptic potentials (EPSPs) produced by repetitive activation of the peripheral afferents or by fast and slow muscle stretch. EPSPs evoked by single electrical stimulation of the tibial nerve or by fast muscle stretch were significantly depressed by PBSt stimulation. However, the last EPSP in a series of EPSPs evoked by a train of electrical stimuli (5-6 shocks, 150-200 Hz) was significantly less depressed by the conditioning stimulation than the first EPSP. In addition, the last part of the long-lasting EPSPs evoked by a slow muscle stretch was also less depressed than the first part. A single EPSP evoked by stimulation of the medial gastrocnemius nerve was less depressed when preceded by a train of stimuli applied to the same nerve than when the same train of stimuli was applied to a synergistic nerve. The decreased sensitivity of the test EPSP to presynaptic inhibition was maximal when it was evoked within 20 ms after the train of EPSPs. It was not observed at intervals longer than 30 ms. These findings suggest that afferent activity may decrease the efficiency of presynaptic inhibition. We propose that the described interaction between afferent nerve activity and presynaptic inhibition may partly explain why electrically and mechanically evoked reflexes are differently sensitive to presynaptic inhibition.     

Reflex pathways from group II muscle afferents

The convergence of group II muscle afferents on interneurones in reflex pathways has been elucidated by investigating interaction in transmission to motoneurones. Recording was also made from interneurones activated from group II afferents. Maximal group II EPSPs evoked in motoneurones from different muscles (extensors or flexors and extensors) did not summate linearly but with a deficit of 35-40%. The corresponding deficit in summation with Ia EPSPs was 7%. It is suggested that the difference in deficit is caused largely by occlusion due to shared interneuronal discharge zones and that it gives an approximate minimal measure of the convergence of group II afferents from different muscles on the interneurones. Tests with weak group II volleys from different muscles gave no or little evidence for spatial facilitation in the disynaptic excitatory pathway to flexor motoneurones, and there was no or little temporal facilitation of transmission in this pathway. It is suggested that group II excitation of the interneurones in this pathway depends on few afferents giving large unitary EPSPs. Convergence of cutaneous afferents and joint afferents on the interneurones was evidenced by spatial facilitation from these afferents of group II transmission to motoneurones. Convergence on interneurones in the trisynaptic inhibitory pathway from group II afferents to extensor motoneurones was also investigated with the spatial facilitation technique. There was convergence on common interneurones of group II afferents from different muscles (extensors or flexors and extensors) and from cutaneous afferents as well as joint afferents. Trisynaptic group II IPSPs, including those depending on spatial facilitation from different muscles were resistant to recurrent depression from motor axon collaterals and are therefore not mediated by the reciprocal Ia inhibitory pathway. Interneurones with monosynaptic group II EPSPs were recorded from in the dorsal horn and intermediate region. Graded stimulation revealed large unitary EPSPs from few group II afferents. The EPSP evoked by a single group II afferent may produce firing (extracellular recording). Convergence of monosynaptic group II EPSPs from different muscles was rather limited but could be from flexors and extensors. Extensive multisensory convergence onto some of these interneurones was indicated by di- or polysynaptic EPSPs from group II and III muscle afferents, from joint afferents and from cutaneous afferents.(ABSTRACT TRUNCATED AT 400 WORDS)     

Responses of cortical neurons to stimulation of corpus callosum in vitro

1. An in vitro slice preparation of rat cingulate cortex was used to analyze the responses of layer V neurons to electrical stimulation of the corpus callosum (CC). In addition, synaptic termination of callosal afferents with layer V neurons was evaluated electron microscopically to provide a structural basis for interpreting some of the observed response sequences. 2. Layer V neurons had a resting membrane potential (RMP) of 60 +/- 0.68 (SE) mV, an input resistance of 47 +/- 4.74 M omega, a membrane time constant of 4.37 +/- 0.51 ms, an electrotonic length constant of 1.38 +/- 0.25, and produced spontaneous action potentials that were 50 +/- 0.3 mV in amplitude. Intracellular depolarizing current pulses evoked spikes that were sometimes associated with low-amplitude (2-5 mV) depolarizing (5-10 ms in duration) and hyperpolarizing (10-20 ms in duration) afterpotentials. 3. A single stimulus of increasing intensities to the CC produced one of the following response sequences: a) antidromic spike and an excitatory postsynaptic potential (EPSP), which initiated one or more spikes; b) antidromic spike, EPSP-evoked action potentials, and a hyperpolarization, which may have represented an intrinsic cell property or inhibitory synaptic activity; c) EPSP and evoked spikes only; d) high-amplitude EPSP with an all-or-none burst of action potentials. 4. Antidromically activated (AA) neurons always produced EPSPs in response to CC stimulation. When compared with nonantidromically activated neurons, AA cells had a more negative RMP, greater electrotonic length constant (LN), higher ratio of dendritic to somatic conductance (rho), and formed shorter duration, callosal-evoked EPSPs. 5. Neurons in anterior cingulate cortex produced EPSPs of longer duration than did those in posterior cortex (50 +/- 3.57 versus 26 +/- 1.56 ms, respectively). EPSPs in anterior neurons also had a higher maximum amplitude (20.5 +/- 1.0 versus 11.5 +/- 0.79 mV) and longer time to peak (11.6 +/- 2.2 versus 8.2 +/- 0.8 ms). 6. Electron microscopy of Golgi-impregnated neurons following contralateral lesions demonstrated that both pyramidal and nonpyramidal neurons received direct callosal afferents. Synaptic termination of callosal axons with the apical dendritic trees of anterior pyramidal cells was 6 times greater than it was with posterior pyramidal neurons. 7. EPSP shape differences in anterior and posterior neurons may be partially accounted for by the density and distribution of callosal afferents to these two cortices.     

Actions of excitatory amino acid antagonists on synaptic potentials of layer II/III neurons of the cat's visual cortex

Summary Actions of excitatory amino acid (EAA) antagonists on the responses of cells in layers II/III and IV of the cat's visual cortex to stimulation of layer VI and the underlying white matter were studied in slice preparations. Antagonists used were 2-amino-5-phosphonovalerate (APV), a selective antagonist for the N-methyl-D-aspartate (NMDA) type of EAA receptors, and kynurenate, a broadspectrum antagonist for the three types of EAA receptors. In extracellular recordings it was demonstrated that most of the layer II/III cells were sensitive to APV, while the great majority of the layer IV cells were not, By contrast, kynurenate suppressed the responses completely in both layers. Excitatory post-synaptic potentials (EPSPs) evoked by stimulation of layer VI and the while matter were recorded intracellularly from layer II/III neurons. To determine whether the EPSPs were elicited mono- or polysynaptically, the synaptic delay for each EPSP was calculated from a pair of onset latencies of EPSPs evoked by stimulation of the two sites. Forty-two percent of the layer II/III cells were classified as having monosynaptic EPSPs. In 60% of these monosynaptic cells, the rising slope of the EPSPs was reduced by APV while in the other 40%, it was not. In the former (APV-sensitive cells), subtraction of the APV-sensitive component from the total EPSP indicated that the onset latency of the NMDA receptor-mediated component was roughly equal to that of the non-NMDA component. In the latter (APV-resistant cells), only the slowly-decaying component was in part mediated by NMDA receptors. The conduction velocities of the afferent fibers innervating APV-resistant cells were slower than those of the APV-sensitive cells, suggesting that both types of cells are innervated by different types of afferents. The polysynaptic EPSPs of almost all layer II/III cells were sensitive to APV. The subtraction method indicated that the NMDA component had about the same magnitude as the non-NMDA components. When the slices were superfused by a Mg²⁺-free solution, the EPSPs were potentiated dramatically, but this potentiation was reduced to the control level during the administration of APV. Similarly, APV-sensitive components were potentiated during the administration of bicuculline, a selective antagonist for gamma-aminobutyric acid receptors of A type. These results suggest that NMDA receptors participate, at varying degrees, in excitatory synaptic transmission at most layer II/III cells in the cat's visual cortex, and their actions appear to be regulated by intracortical inhibition.     

Presynaptic modulation by GABAB receptors of glutamatergic excitation and GABAergic inhibition of neostriatal neurons.

1. The present experiments investigated the effects of gamma-amino-butyric acidB (GABAB) receptor stimulation on the excitatory and inhibitory responses of neostriatal neurons evoked by stimulation of the subcortical white matter in a rat neostriatal slice preparation. 2. Intracellular recordings showed that single-impulse stimulation of the corpus callosum evoked monosynaptic, 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX)-sensitive excitatory postsynaptic potentials (EPSPs) that were attenuated by the GABAB receptor agonist, p-chlorophenyl-GABA (baclofen, 0.5-10 microM) in a concentration-dependent manner. Baclofen also blocked the GABAA-mediated inhibition of neostriatal cell responses, which were revealed by paired-impulse stimulation of the subcortical white matter. Both of these effects persisted in slices in which the anterior cortex was removed, indicating that the site of action for baclofen was intrinsic to the neostriatum. The GABAB antagonist 3-amino-2-hydroxy-2-(4-chlorophenyl)-propanesulfonic acid (saclofen, 250-500 microM) reversed the depressant actions of baclofen on both the excitatory and inhibitory responses of neostriatal cells. 3. Concentrations of baclofen as high as 100 microM, which markedly attenuated EPSP amplitude, did not exert direct effects on resting membrane potential, current-voltage relationship, input resistance, or spike threshold and thus appeared to have no postsynaptic effect on the population of neurons recorded. 4. These results indicate that, in contrast to other regions of the CNS, the depressant effects of baclofen on glutamate-dependent EPSPs are mediated exclusively through GABAB receptors located presynaptically on the terminals of glutamatergic afferents.(ABSTRACT TRUNCATED AT 250 WORDS)     

Linear to supralinear summation of AMPA-mediated EPSPs in neocortical pyramidal neurons

It has been hypothesized that voltage-sensitive conductances present on the dendrites of neurons can influence summation of excitatory postsynaptic potentials (EPSPs) and hence affect how neurons compile information. Greater than linear summation of EPSPs has been postulated to facilitate coincidence detection by cortical neurons. This study examined whether the summation of subthreshold AMPA-mediated EPSPs generated on layer V neocortical pyramidal neurons in vitro was linear and if any nonlinearities could be attributed to dendritic conductances. Evoked EPSPs (1-12 mV) were recorded somatically by means of intracellular sharp electrodes in the presence of 100 microM amino-5-phosphonopentanoic acid (AP-5) and 3 microM bicuculline. Two independent EPSPs were evoked by a stimulating electrode in layer I and another in layers III-V. The areas of stimulation were isolated from each other by a horizontal cut below layer I. By subtracting the algebraic sum of the individual EPSPs from the evoked response when both EPSPs were evoked simultaneously, we determined that they summed linearly to supralinearly. Supralinear summation was more likely when the soma was hyperpolarized by DC current injection. Summation was predominantly linear when postsynaptic conductances (i.e., Na(+) and Ca(2+)) were blocked with intracellular QX-314. The supralinear summation of EPSPs (without QX-314) decreased as the time between inputs was increased from 0 to 30 ms. To determine the role of dendrites in nonlinear summation, we substituted a current pulse (simulated EPSP) delivered at the soma for either or both of the evoked EPSPs. Simulated EPSPs combined with either an evoked EPSP or another simulated EPSP showed significantly less supralinear summation than two evoked EPSPs, indicating that the dendritic conductances were largely responsible for the observed supralinear summation.     

Inputs from regularly and irregularly discharging vestibular nerve afferents to secondary neurons in the vestibular nuclei of the squirrel monkey. I. An electrophysiological analysis

1. The electrical excitability of vestibular nerve afferents is related to their discharge regularity (23). Irregular (I) afferents are more excitable than regular (R) afferents. We explored the possibility that the differences in electrical excitability could be used to determine the profile of monosynaptic inputs from the ipsilateral vestibular nerve (Vi) to secondary neurons of the vestibular nuclei. The growth of monosynaptic Vi excitatory postsynaptic potentials (EPSPs) as shock strength is increased should reflect the kinds of afferent input that a secondary neuron receives. We were particularly interested in seeing if cells in the vestibular nuclei could be distinguished as R or I neurons depending on whether they received predominantly regular or irregular inputs. Barbiturate-anesthetized squirrel monkeys were used. 2. Recordings were made from vestibular nerve afferents. Shock strength was expressed as multiples of T, the value needed to recruit 10% of the afferents or, as determined empirically, to evoke a detectable field potential in the vestibular nuclei. Most I afferents (85/87 = 98%) were recruited below 4 X T, whereas most R afferents (197/212 = 93%) were first activated above 4 X T. The relation between latent period and electrical excitability was flat for units with thresholds in the range 1-4 X T. Latent periods increased for units with higher thresholds, especially those first activated above 8 x T. The threshold differences between I and R afferents are maximal if the shock falls at approximately half the mean interval after a naturally occurring action potential. The same results were obtained by having each unit fire to a maximal (16-32 X T) conditioning shock and then determining the threshold to a test shock presented 4 ms later. The latter stimulus configuration was used to study the Vi monosynaptic inputs to secondary neurons. The test shock was raised by successive doublings from 1 X T to the strength of the conditioning shock (16-32 X T). 3. Intracellular recordings were made from neurons located in the superior vestibular nucleus or the rostral parts of the medical or lateral vestibular nuclei. Amplitudes and latent periods of Vi EPSPs were measured from averages of several repetitions of each stimulus pair. Each EPSP was calculated by subtracting the extracellular from the intracellular averaged response. Of the 122 neurons sampled, 115 were judged to be monosynaptically related to the ipsilateral vestibular nerve because their Vi EPSPs had latent periods in the range of 0.7-1.4 ms.(ABSTRACT TRUNCATED AT 400 WORDS)