Synaptic linkage of masseter muscle afferents to masseteric motoneurones in the cat

The synaptic linkage of masseter muscle afferents to masseteric motoneurones was investigated under blockage of soma-dendritic invasion of antidromic spikes by passing constant inward current across the cell membrane. A monosynaptic latency for excitatory postsynaptic potentials produced by group Ia afferents was measured as 1.3 ms and no group lb component was obtained. Inhibitory postsynaptic potentials with latencies of 5.5 ms were produced at a stimulus strength of 4.5 times the threshold of group Ia fibers. On the basis of stimulus strength, muscle afferents activated at 4.5 times the threshold and producing inhibitory postsynaptic potentials in masseteric motoneurones are probably group II afferents. The same reversal point was obtained in both the lingually induced and the group II IPSPs, indicating that the group II inhibitory postsynaptic potential is dependent on an increased permeability to Cl ions. The inhibitory postsynaptic potentials produced by stimulation of the high threshold muscle afferents were the composite of a strychnine-sensitive and strychnine-insensitive inhibitory postsynaptic potential. The latency of the inhibitory postsynaptic potentials caused by the high threshold muscle afferents was about 10 ms.     

The effect of transection and cold block of the spinal cord on synaptic transmission between Ia afferents and motoneurones

Composite excitatory postsynaptic potentials were elicited in lumbar motoneurones by Ia afferents from muscles of the triceps surae group. These excitatory postsynaptic potentials were examined in the same cell before, during and after interruption of descending spinal pathways. After transection or cold block of the spinal cord at T12-T13, the amplitude of composite excitatory postsynaptic potentials showed no significant change for a period of up to seven hours after transection. However, there was a reduction in amplitude of the monosynaptic reflex in the extensor motoneurones which may be due to an observed hyperpolarization and reduction in membrane time constant in these neurones. The reduction in amplitude of the monosynaptic reflex observed in spinal shock can be attributed to the effects of these changes, rather than to a decrease in the size of the monosynaptic excitatory postsynaptic potential.     

The ionic mechanism of postsynaptic inhibition in motoneurones of the frog spinal cord

The ionic mechanism of postsynaptic inhibition in frog spinal motoneurones was studied with conventional and with ion-sensitive microelectrodes. In these neurones the inhibitory postsynaptic potential was depolarizing, its reversal potential being 15 mV less negative than the resting membrane potential. During the inhibitory postsynaptic potential the input resistance of the motoneurones was reduced to 20% of the resting value, indicating a strong increase of membrane conductance. The Cl- equilibrium potential calculated from intra- and extracellular Cl- activity measurements coincided with the reversal potential of the inhibitory postsynaptic potential to within a few millivolts. During repetitive inhibitory postsynaptic activity the intracellular Cl- activity decreased markedly, while the extracellular Cl- activity increased slightly. These changes of intra- and extracellular Cl- activities were no longer found after suppression of the inhibitory postsynaptic potential by strychnine. Blockade of an active, inward-going Cl- transport system in motoneurones by NH+4 led to a shift of the Cl- equilibrium potential and the reversal potential of the inhibitory postsynaptic potential towards the resting membrane potential. After prolonged action of NH+4, the Cl- equilibrium potential approached the membrane potential to within 5 mV, while the reversal potential of the inhibitory postsynaptic potential and resting membrane potential coincided. The difference between Cl- equilibrium potential and membrane potential after blockade of the Cl- pump is traced back to interfering intracellular ions, such as HCO-3 or SO42-, leading to an overestimation of intracellular Cl- activity and to the calculation of an erroneous Cl- equilibrium potential. Inhibitory amino acids like gamma-aminobutyrate or beta-alanine evoked depolarizations with reversal potentials similar to that of the inhibitory postsynaptic potential. These depolarizations were associated with a marked decrease of neuronal input resistance during inhibition. During the actions of these compounds a decrease of intracellular and a small increase of extracellular Cl- activity were found. The activities of other ions (K+, Ca2+ and Na+) did not change significantly, with the exception of extracellular K+ activity, which was slightly increased. Evidence is presented that the inhibitory postsynaptic potential, as well as the depolarizing action of inhibitory amino acids in motoneurones, is the result of an increase in membrane Cl- permeability and an efflux of Cl- from these cells, while other ions do not seem to be involved.     

Depression of monosynaptic excitatory postsynaptic potentials by Mn2+ and Co2+ in cat spinal cord.

In cats anesthetized with allobarbitone-urethane, Mn²⁺ and Co²⁺ (and occasionally La³⁺) were released extracellularly from micropipettes while recordings were made of monosynaptic excitatory postsynaptic potentials evoked in lumbosacral motoneurones by Ia afferent stimulation. These excitatory postsynaptic potentials consistently showed a marked depression in their rate of rise (by an average of 44%) and an increase in half-amplitude duration (by an average of 50%). There was a less pronounced reduction in peak amplitude and increase in time-to-peak. After applications of Mn²⁺ or Co²⁺, presynaptic potentials recorded in motoneurones showed no sign of any depression but the synaptic delay was clearly increased.It is concluded that the monosynaptic excitatory postsynaptic potential evoked by Ia afferents in cat motoneurones is probably mediated by chemical transmission.     

Slow postsynaptic potentials in neurones of submucous plexus of guinea-pig caecum and their mimicry by noradrenaline and various peptides

Intracellular recordings of membrane potential and membrane currents were made from neurones in the submucous plexus of the guinea-pig caecum in vitro. Fast and slow excitatory postsynaptic potentials and slow inhibitory postsynaptic potentials were recorded from the majority of neurones following focal stimulation of presynaptic fibres in the plexus. The slow inhibitory postsynaptic potential was associated with an increase in membrane conductance and reversed its polarity at -90 mV; it was reversibly blocked by yohimbine. The slow excitatory postsynaptic potential and its underlying current was associated with a decrease in membrane conductance. Two kinds of voltage-dependence both of the slow excitatory postsynaptic potential and current were observed; in 80% of cells, the excitatory postsynaptic potential and current became smaller with membrane hyperpolarization and reversed polarity at -90 mV (reversing type) but in 20% of cells both the excitatory postsynaptic potential and current simply disappeared when the membrane potential reached -70 mV (non-reversing type). The effects of acetylcholine, adenosine 5'-triphosphate, bombesin, 5-hydroxytryptamine, neurotensin, noradrenaline, substance P and vasoactive intestinal polypeptide were examined. The only substance which mimicked the slow inhibitory postsynaptic potential was noradrenaline; brief applications of noradrenaline caused hyperpolarizations which had the same time-course, reversal potential and sensitivity to yohimbine as the slow inhibitory postsynaptic potential. The non-reversing type of slow excitatory postsynaptic potential was mimicked only by adenosine 5'-triphosphate. The reversing type of slow excitatory postsynaptic potential was mimicked by bombesin, neurotensin, substance P and vasoactive intestinal polypeptide. 5-Hydroxytryptamine and vasoactive intestinal polypeptide (in some neurones) caused a depolarization with an increase in membrane conductance. All three synaptic potentials were reversibly depressed by superfusion of noradrenaline but noradrenaline did not affect the potential changes evoked by brief application of exogenous acetylcholine or substance P. It is concluded that, in guinea-pig submucous plexus neurones, the slow inhibitory postsynaptic potential is mediated by noradrenaline and results from a potassium conductance increase.(ABSTRACT TRUNCATED AT 400 WORDS)     

Mechanisms regulating the activity of facial nucleus motoneurones--2. Synaptic activation from the caudal trigeminal nucleus

Field and postsynaptic potentials of facial motoneurones evoked by stimulation of the caudal trigeminal nucleus were studied in cats by means of extra- and intracellular recording. Mono- and polysynaptic input onto facial motoneurones from the caudal trigeminal nucleus were shown. Four types of responses were distinguished: excitatory postsynaptic potentials generating a single action potential; a gradual shift of depolarization inducing multiple discharges; a rhythmic discharge of action potentials appearing at a low level of depolarization; excitatory postsynaptic potentials or a sequence of excitatory and inhibitory postsynaptic potentials. Multiple discharge was shown to appear as a result of effective summation of high frequency excitatory influences from efferent neurones of the caudal trigeminal nucleus projecting into the facial nucleus. Factors facilitating the development of gradual depolarization are: dendritic localization of synaptic terminals, dendritic origin of after-depolarizing processes and the high input resistance of the facial motoneurone membrane. It is thought that specific features of facial motoneurones and properties of afferent inputs are supposed to provide high sensitivity of neuronal organization of the facial nucleus to afferent signals as well as wide diversity in controlling its activity.     

Developmental changes in presynaptic muscarinic modulation of excitatory and inhibitory neurotransmission in rat piriform cortex in vitro: relevance to epileptiform bursting susceptibility

Suppression of depolarizing postsynaptic potentials and isolated GABA-A receptor-mediated fast inhibitory postsynaptic potentials by the muscarinic acetylcholine receptor agonist, oxotremorine-M (10 microM), was investigated in adult and immature (P14-P30) rat piriform cortical (PC) slices using intracellular recording. Depolarizing postsynaptic potentials evoked by layers II-III stimulation underwent concentration-dependent inhibition in oxotremorine-M that was most likely presynaptic and M2 muscarinic acetylcholine receptor-mediated in immature, but M1-mediated in adult (P40-P80) slices; percentage inhibition was smaller in immature than in adult piriform cortex. In contrast, compared with adults, layer Ia-evoked depolarizing postsynaptic potentials in immature piriform cortex slices in oxotremorine-M, showed a prolonged multiphasic depolarization with superimposed fast transients and spikes, and an increased 'all-or-nothing' character. Isolated N-methyl-d-aspartate receptor-mediated layer Ia depolarizing postsynaptic potentials (although significantly larger in immature slices) were however, unaffected by oxotremorine-M, but blocked by dl-2-amino-5-phosphonovaleric acid. Fast inhibitory postsynaptic potentials evoked by layer Ib or layers II-III-fiber stimulation in immature slices were significantly smaller than in adults, despite similar estimated mean reversal potentials ( approximately -69 and -70 mV respectively). In oxotremorine-M, only layer Ib-fast inhibitory postsynaptic potentials were suppressed; suppression was again most likely presynaptic M2-mediated in immature slices, but M1-mediated in adults. The degree of fast inhibitory postsynaptic potential suppression was however, greater in immature than in adult piriform cortex. Our results demonstrate some important physiological and pharmacological differences between excitatory and inhibitory synaptic systems in adult and immature piriform cortex that could contribute toward the increased susceptibility of this region to muscarinic agonist-induced epileptiform activity in immature brain slices.     

Spatial synaptic distribution of recurrent and group Ia inhibitory systems in cat spinal motoneurones

1. The reversal potentials of several types of inhibitory post-synaptic potentials (IPSPs) have been studied in cat spinal motoneurones with and without modification of intracellular chloride ion (Cl(-)) concentration. Single barrel intracellular micropipette electrodes have been used.2. When studied with potassium citrate filled micropipettes, the reversal potential for IPSPs evoked by stimulation of antagonist group Ia afferents is the same as that for recurrent IPSPs evoked by antidromic stimulation of motoneurone axon collaterals, confirming earlier observations (Araki, Ito & Oscarsson, 1961; Coombs, Eccles & Fatt, 1955).3. Studied with potassium chloride filled micropipettes. the reversal potential for the group Ia IPSP was found to be different from that for the recurrent IPSP when the amount of Cl(-) diffusing or iontophoretically injected into the motoneurone was small. The amount of difference in reversal potential varied from cell to cell but when present the group Ia IPSP reversed to a depolarizing potential more readily than the recurrent IPSP in all cases.4. Interaction between recurrent IPSPs and monosynaptic excitatory post-synaptic potentials (EPSPs) was also studied and the amount of non-linearity of potential summation was measured.5. The results are consistent with the hypothesis that the terminations of Renshaw cells responsible for the recurrent IPSP are located largely on the proximal dendrites of motoneurones, while the terminations of the interneurones generating the group Ia IPSP appear to be closer to or on the cell somata.     

Oscillations of the spontaneous slow-wave sleep rhythm in lateral geniculate nucleus relay neurons of behaving cats

Intracellular recordings of 31 lateral geniculate nucleus relay neurons were performed in darkness in behaving cats in order to analyse electrical postsynaptic events which appeared during slow-wave sleep. A specific pattern characterized slow-wave sleep: a rapid depolarizing potential arising from baseline initiated a slow depolarization lasting for 40-60 ms which in turn most often elicited delayed fast spikes. This pattern recurred at a frequency of 6-12/s. The slow depolarizations were voltage dependent, usually not separated by any obvious phasic hyperpolarization and showed refractoriness. Other rapid depolarizing potentials occurring during the time course or at the end of a slow depolarization could have generated spike(s) but were followed by a rapid decay. Slow depolarizations were not observed during arousal or paradoxical sleep when the neurons tonically depolarized and displayed either rapid depolarizing potentials with a fast decay or repetitive firing and long high frequency bursts. In five of the studied neurons, decreases in frequency of the spontaneous rapid depolarizing potentials occurred during slow-wave sleep for 3-30 s oscillatory periods without any change in the behavioural state. During these periods all of the few remaining rapid depolarizing potentials arose from a flat baseline, had a higher amplitude and initiated a slow depolarization which always elicited a spike or burst of spikes after a brief delay. The slow-wave sleep rhythm decreased to 1-5/s. Simultaneously the baseline membrane potential hyperpolarized by a few millivolts and reached a level for reversal of inhibitory postsynaptic potentials. Imposed hyperpolarization of the membrane during wakefulness did not reveal any slow depolarization. But strong synaptic excitatory inputs and direct excitation (a break of the current pulse) from a hyperpolarized membrane did evoke the slow depolarization and eventually the fast spike(s) in both control and oscillatory neurons. A rhythm similar to that of slow-wave sleep was elicited during wakefulness by optic tract stimulation and was enhanced by membrane hyperpolarization. But under these conditions the rhythm was initiated by a phasic hyperpolarization and was composed of an alternating hyperpolarization-depolarization. Spontaneously and synaptically evoked rapid depolarizing potentials arising from baseline had a similar rising slope. The spontaneous ones initiated a slow depolarization leading to fast spike(s) during slow-wave sleep and could directly generate fast spike(s) during wakefulness.(ABSTRACT TRUNCATED AT 400 WORDS)     

Neuromuscular transmission in the visceral muscle of locust oviduct

Innervation of the locust oviduct has been investigated with morphological and electrophysiological methods. Using Co2+ and Ni2+ labelling technique, it was found that G7 N2B1 and B2a nerves innervate the oviduct musculature. Ultrastructurally two different terminals could be distinguished: (a) nerve endings containing mainly clear vesicles forming neuromuscular junctions with the muscle fibers; and (b) nerve terminals containing electron-dense granules which showed only "synaptoid" structures, but failed to form junctions with the muscle cells. The neuromuscular junctions proved to be functioning, since it was possible to record intracellularly miniature excitatory postsynaptic potentials and excitatory postsynaptic potentials from the muscle cells. The distribution of the amplitudes of the miniature excitatory postsynaptic potentials suggests a multiterminal innervation. Following electrical stimulation of N2B nerve, excitatory postsynaptic potentials similar to those appearing spontaneously could be evoked. After repetitive stimulation, facilitation or summation of excitatory postsynaptic potentials was observed. The results obtained show that locust oviduct muscle has a double, motor and modulatory innervation.     

Dual transmission at morphologically mixed synapses: Evidence from postsynaptic cobalt injections

Two experimental approaches have been utilized to test the possibility that morphologically mixed synaptic terminals of the eighth nerve fibers mediate both electrotonic and chemical excitation of the goldfish Mauthner cell. First, the spatial distributions of electrotonic and chemical postsynaptic potentials, evoked by stimulation of the eighth nerve, have been determined with intracellular recordings from the Mauthner cell soma and several locations along the lateral dendrite. In some instances, both synaptic components were maximal at distal dendritic recording sites. In that region, it appears that the only presynaptic terminals with morphological characteristics consistent with excitatory chemical transmission are the large myelinated club endings, which actually establish mixed synapses with the lateral dendrite. Second, we have analyzed the effects of postsynaptic Co²⁺ injections on these synaptic responses. With high iontophoretic currents, there was a rapid uncoupling of the electrotonic component. However, with smaller current intensities, uncoupling is accompanied, or preceded, by a transient reduction in the later chemically mediated postsynaptic potentials. This latter effect on chemical transmission is only observed if the postsynaptic potentials are associated with electrotonic synaptic inputs. We speculate that Co²⁺ diffuses across the gap junctions and into the presynaptic terminals, acting there to reduce evoked transmitter release.The results of these two experimental approaches support the hypothesis that mixed synapses on the lateral dendrite of the Mauthner cell do actually mediate transmission by both chemical and electrical modes.     

Characterization of synaptic transmission in the ventrolateral periaqueductal gray of rat brain slices

Synaptic transmission evoked by focal stimulation in the ventrolateral periaqueductal gray was characterized using the whole-cell recording technique in rat brain slices. At resting membrane potential (-62+/-1 mV), focal stimulation (0.05-0.1 ms, 0.03 Hz) usually evoked a 6-cyano-7-nitroquinoxaline-2, 3-dione-sensitive fast excitatory postsynaptic potential and a DL-2-amino-5-phosphonopentanoic acid-sensitive slow excitatory postsynaptic potential with a bicuculline-sensitive inhibitory postsynaptic potential in between. In the presence of kynurenic acid, bicuculline-sensitive inhibitory postsynaptic currents recorded in the voltage-clamp mode displayed a reversal potential of -68+/-3 mV, resembling GABA(A) receptor-mediated inhibitory postsynaptic currents. However, no GABA(B) receptor-mediated inhibitory postsynaptic current was evoked, even at stronger stimulating intensity. 6-Cyano-7-nitroquinoxaline-2,3-dione-sensitive fast excitatory postsynaptic currents were isolated by DL-2-amino-5-phosphonopentanoic acid plus bicuculline and DL-2-amino-5-phosphonopentanoic acid-sensitive slow fast excitatory postsynaptic currents by bicuculline plus 6-cyano-7-nitroquinoxaline-2,3-dione. Both types of excitatory postsynaptic current reversed at potentials near 0 mV. The I-V curve of slow fast excitatory postsynaptic currents or N-methyl-D-aspartate currents displayed a negative slope at potentials more negative than -30 mV in an Mg(2+)-sensitive manner. The control postsynaptic currents reversed at potentials between -50 and -35 mV, inclined to the reversal potential of GABA(A), but not glutamate, receptor channels. It is concluded that, in the ventrolateral periaqueductal gray, focal stimulation elicits both inhibitory and excitatory transmission, while the former is dominant. The inhibitory transmission is mediated by GABA(A) but not GABA(B) receptors. The excitatory transmission is mediated by glutamate acting on alpha-amino-3-hydroxy-5-methylisoxazole-4-propionate/kainate as well as N-methyl-D-aspartate receptors.     

Disynaptic brainstem—propriospinal projections to mammalian motoneurones

In experiments carried out on cats simultaneous recording from hindlimb motoneurones and propriospinal interneurones receiving monosynaptic inputs from the brain stem was accomplished. The recording of the unitary postsynaptic potentials produced in motoneurones by direct stimulation of individual propriospinal cells has shown that supraspinal projections can govern spinal motor centres via propriospinal cells that establish direct monosynaptic contacts with alpha-motoneurones.     

Frequency-to-voltage conversion in the pyramidal tract neuron: an important role of the inhibitory postsynaptic potential

Frequency-coded impulses are known to be converted into postsynaptic potentials (PSPs) at the synapse of a target neuron. This can be termed frequency-voltage (F-V) conversion. Studies on this problem in pyramidal tract neurons (PTNs) showed that not only the amplitude but also the duration of depolarizing PSPs was determined as a function of the input impulse frequency. Two opposite patterns of F-V conversion were observed following activation of two input systems to PTNs. Inhibitory postsynaptic potentials were found to play an important role in the regulation of the duration of PSPs by curtailing excitatory post-synaptic potentials.     

Depolarization of cortical glial cells in response to electrical stimulation of the cortical surface

The responses of 155 neurones and 91 glial cells to the electrical stimulation of the cortex were recorded in the suprasylvian gyrus of 20 cats under pentobarbital anaesthesia. Glial cells were identified by electrophysiological criteria: absence of action potentials and postsynaptic potentials; high membrane potential; slow depolarization during the electrical stimulation of the cortex. 50 glial cells showed membrane potentials between 80 and 100 mV. Stimuli of low intensity which evoked only excitatory postsynaptic potentials of apical dendrites, the so-called dendritic potentials, failed to evoke glial depolarization. However, glial depolarization could be elicited at high-frequency stimulation. Stimuli, which evoked not only the dendritic potential but also subsequent slow negativity, could usually bring about glial depolarization too. The amplitude of glial depolarization in response to one stimulus did not exceed 2 mV, the latency being 3–5 ms. A phenomenon of decrementai summation of glial depolarization was observed. The stronger and more frequent the stimulation, the larger was glial depolarization. However, at frequencies over 50/s glial depolarization decay was observed already during the stimulation and in some cases, membrane potential was drastically reduced to zero. After cessation of stimulation, glial depolarization decayed exponentially in 3–4 s; in some cases the decay was prolonged up to 10s and slow irregular fluctuations of the membrane potential were recorded; at the same time, spikes of the neighbouring neurone could be recorded from the glial cell. With a decrease of the membrane potential glial depolarization was attenuated, but it could be elicited even at membrane potential below 20 mV.The results are interpreted in relation to the potassium ion hypothesis. It is suggested that glial depolarization is determined by release of K⁺, which is associated with excitation of non-myelinated fibres and with excitatory postsynaptic potentials generated in the cortical neuropile. Significant increases in the concentration of extracellular potassium ions could provoke actual movement of glial cells. It is supposed that glial depolarization of small magnitude which is recorded occasionally at the membrane potential below 30 mV is the result of electronic spread of glial depolarization from the neighbouring glial cells.     

Cortically induced postsynaptic potentials in hypoglossal motoneurons after axotomy

Cortically induced postsynaptic potentials were studied in normal and axotomized cat hypoglossal motoneurons. In normal protruder motoneurons innervating tongue protruder muscles, we have demonstrated that stimulation of the orbital gyrus, at the point optimum for inducing lapping movements of the tongue by repetitive stimuli, produced inhibitory postsynaptic potentials or excitatory postsynaptic potentials followed by predominant inhibitory postsynaptic potentials. The cortically induced excitatory postsynaptic potential in normal protruder motoneurons was composed of only the short-latency component. In protruder motoneurons 30, 40, 60 and 80 days after axotomy, we have demonstrated that the number of protruder motoneurons responding with two components of excitatory postsynaptic potentials (the short- and the long-latency component) to cortical stimulation increased in correspondence with the lapse of days after axotomy and that the amplitude of cortically induced inhibitory postsynaptic potentials in axotomized protruder motoneurons was reduced in size as compared with normal protruder motoneurons.     

Computer simulations indicate that electrical field effects contribute to the shape of the epileptiform field potential

In the presence of convulsant drugs such as picrotoxin, neurons in the hippocampal-slice preparation generate synchronized depolarizing bursts. This synchrony occurs on a time scale of tens of milliseconds and is produced by excitatory synaptic interactions between neurons. The synaptic interactions themselves occur on a time scale of tens of milliseconds. The "epileptiform" local-field potential during such synchronized bursts is comb-shaped ("ringing"), whereas the field potential expected if action potentials in neighboring neurons were uncorrelated is noisy and not comb-shaped. This suggests that individual action potentials are locally synchronized on a time scale of 1 ms. We have previously shown, using computer simulations, that electrical interactions--mediated by currents flowing in the extracellular medium--can plausibly explain action-potential synchronization in experiments where chemical synapses are blocked. The present simulations demonstrate that electrical interactions can also account for action-potential synchronization--and thus the "ringing" shape of the field potential--during epileptiform bursts, where excitatory synapses are functional. The field potential is thus a modulating influence on, as well as a reflection of, underlying neuronal transmembrane events.     

The distribution of monosynaptic excitation from the pyramidal tract and from primary spindle afferents to motoneurones of the baboon's hand and forearm

1. Intracellular records were obtained from motoneurones innervating muscles of the baboon's forearm and hand. Monosynaptic excitatory postsynaptic potentials (EPSPs) were elicited by stimulation of motor cortex (CM EPSPs) and peripheral nerves (Ia EPSPs).

2. CM EPSPs were larger on average in motoneurones innervating intrinsic hand muscles and extensor digitorum communis (EDC) than in neurones of other forearm muscles.

3. Among motoneurones of the median nerve, the CM EPSP tended to be larger for cells with more rapidly conducting axons than for those with more slowly conducting axons. Among motoneurones of EDC the opposite tendency was found.

4. The afferent fibres responsible for the Ia EPSP nearly always had a lower stimulus threshold than that of motor axons in the same nerve. Some observations were made concerning the distribution of heteronymous Ia EPSPs.

5. Among motoneurones of a given nerve, those with large Ia EPSPs tended to receive larger CM EPSPs than did cells in which the Ia EPSP was small.

6. The results are discussed in relation to problems concerning the pyramidal control of hand and finger movement.

     

Fast hyperpolarization following an excitatory postsynaptic potential in cat bladder parasympathetic neurons

Intracellular recording techniques were used to study a fast hyperpolarizing potential following the fast excitatory postsynaptic potential evoked by an orthodromic nerve stimulation in cat bladder parasympathetic ganglion cells. In the 61 ganglion cells examined, two types of responses were recorded on stimulating the preganglionic nerve; one had only a fast excitatory postsynaptic potential (type SI, n = 20) and the other had a fast excitatory postsynaptic potential followed by a fast hyperpolarizing potential (type SII, n = 41). In type SII neurons, the half-maximum duration of the afterhyperpolarizing potential following an orthodromic spike was longer than that of a direct spike produced by injecting a depolarizing current pulse through the recording electrode; the half-maximum durations for afterhyperpolarizing potentials following orthodromic and direct action potentials were comparable in type SI cells. Blocking the initiation of an orthodromic spike by hyperpolarizing the membrane in type SII cells revealed a fast excitatory postsynaptic potential followed by a fast hyperpolarizing potential which was similar to that observed at the resting potential. The fast hyperpolarizing potential had a duration comparable to that of an afterhyperpolarizing potential following an orthodromic action potential.

The fast excitatory postsynaptic potential-fast hyperpolarizing potential sequence was blocked completely and reversibly by nicotinic receptor antagonists (hexamethonium andd-tubocurarine). Atropine, alpha-2 noradrenergic (yohimbine and phentolamine), and purinergic (caffeine) antagonists had no effect on the fast hyperpolarizing potential. In cells which show type SII responses, spontaneous excitatory postsynaptic potentials were not followed by a hyperpolarization. Depolarizing the membrane (by passing a cathodal current through the recording electrode) to an amplitude comparable to that of a fast excitatory postsynaptic potential also did not elicit a membrane hyperpolarization in type SII cells. In some cells, stimulating one preganglionic nerve trunk elicited a fast hyperpolarizing potential, but activating another nerve trunk innervating the same ganglion cell did not. There was no correlation between the variations in the amplitudes of the fast excitatory postsynaptic potential and the fast hyperpolarizing potential in type SII cells, but increasing the stimulus intensity applied to the presynaptic nerve fiber potentiated the amplitude of the fast excitatory postsynaptic potential and the fast hyperpolarizing potential. The fast hyperpolarizing potential was not associated with appreciable changes in input resistance. When the membrane was hyperpolarized, the amplitude of the fast excitatory postsynaptic potential increased, but that of the fast hyperpolarizing potential decreased. A reversal potential for the fast hyperpolarizing potential was not observed.

These results indicate that the afterhyperpolarizing potential following an orthodromic action potential in many parasympathetic neurons of the cat bladder has a hyperpolarizing synaptic component, the fast hyperpolarizing potential, which is not correlated with the fast excitatory postsynaptic potential initiating the spike. It is suggested that the fast hyperpolarizing potential is due to passive decay of the afterhyperpolarizing potential following an action potential, caused by acetylcholine released from nerve terminals in regions remote from the soma, probably distal dendrites.     

Action of baclofen on mammalian synaptic transmission.

Microiontophoretic and systemic injections were used to investigate the mechanism of baclofen's powerful depressant action on transmission at primary afferent synapses in the cat. Iontophoretic applications depressed the spontaneous and evoked activity of cuneate cells and reduced the excitability and input resistance of spinal motoneurones. These effects, which were quick to reverse, resemble those of γ-aminobutyrate and may be due to activation of γ-aminobutyrate receptors by high concentrations of baclofen. Systemic doses of baclofen (0.1–5 mg/kg i.V.), which are known to give only a very low tissue concentration (<10^?7M), induced a very prolonged depression of synaptic responses in the spinal cord (motoneuronal excitatory postsynaptic potentials) and the cuneate nucleus (medial lemniscal potentials); but there was no increase in motoneuronal conductance, and responses of cuneate neurones to direct stimulation by electrical pulses, glutamate, or substance P were not diminished. On the other hand, there was some reduction in the excitability of primary afferent fibres, and the dorsal column reflex and primary afferent depolarization (as revealed by tests of terminal excitability) were nearly abolished.These observations are most simply explained if systemic baclofen blocks primary afferent synapses by a presynaptic action, which leads to a depression of transmitter release; this would be in keeping with evidence that, in cortical slices, baclofen selectively inhibits the release of excitatory amino acids.