Cardioregulatory nerves in the spider Eurypelma marxi Simon

The objective of this study was to locate nerves arising from the CNS that have a cardioregulatory function in the tarantula, Eurypelma marxi Simon. Ramifications of the paired abdominal nerve VIIIb merge with the cardiac ganglion within the first heart segment. Electrical stimulation of the branches of nerve VIIIb that connect with the cardiac ganglion produce changes in heartbeat rate and amplitude. Nerve cutting experiments indicate that no other cardioregulatory nerves are present. Both increases and decreases in heart activity can be produced upon electrical stimulation of nerve VIIIb on each side of the heart. Only one action potential associated with the response of each type could be recorded in each member of the nerve pair. Therefore, we conclude that there are two inhibitory and two acceleratory neurons that arise in the central nervous system to modulate heartbeat activity. The inhibitory effect becomes maximal at a stimulation frequency of 20-30 Hz and the accelerator effect at 30-40 Hz. The aftereffect of acceleratory nerve activity exceeds that of inhibitory nerve activity. When the inhibitor and accelerator are activated simultaneously, the inhibitor dominates. The regulatory nerves interact with neurons in the cardiac ganglion. During inhibition, the number of externally recorded spikes in each ganglionic burst is decreased. The rate and magnitude of the heartbeat are decreased concomitantly. Stimulation of the accelerator enhances electrical activity in the cardiac ganglion at the same time that the heartbeat rate and amplitude are increased.     

Acceleratory Synapses on Pacemaker Neurons in the Heart Ganglion of a Stomatopod, Squilla oratoria

The pacemaker neurons of the heart ganglion are innervated from the CNS through two pairs of acceleratory nerves. The effect of acceleratory nerve stimulation was examined with intracellular electrodes from the pacemaker cells. The major effects on the pacemaker potential were an increase in the rate of rise of the spontaneous depolarization and in the duration of the plateau. The aftereffect of stimulation could last for minutes. No clear excitatory postsynaptic potential (EPSP) was observed, however. On high frequency stimulation, a small depolarizing response (the initial response) was sometimes observed, but the major postsynaptic event was the following slow depolarization, or the enhancement of the pacemaker potential (the late response). With hyperpolarization the initial response did not significantly change its amplitude, but the late response disappeared, showing that the latter has the property of the local response. The membrane conductance did not increase with acceleratory stimulation. The injection of depolarizing current increased the rate of rise of the spontaneous depolarization, but only slightly in comparison with acceleratory stimulation, and did not increase the burst duration. It is concluded that the acceleratory effect is not mediated by the EPSP but is due to a direct action of the transmitter on the pacemaker membrane.     

THE ACTION OF INHIBITORY NERVES ON CARBON DIOXIDE PRODUCTION IN THE HEART GANGLION OF LIMULUS

It has been shown in this paper that stimulation of the inhibitory nerves of the neurogenic heart of Limulus, which correspond to the vagus nerves of the vertebrate heart, results in a marked diminution of CO₂ production in the heart ganglion, while stimulation of the ganglion, leading to increased activity of the heart, leads also to increased CO₂ production by the ganglion. This shows that inhibition of the automaticity of this ganglion by the action of its inhibitory nerves consists, not in a process of blocking, but in a diminution of those chemical reactions in the ganglion cells which give rise to the production of CO₂.     

Cardioacceleratory reflexes triggered by mechanoproprioceptors of the swimmerets in the stomatopod crustacean Squilla oratoria

The heart of Squilla oratoria is innervated by processes arising from the cardiac ganglion, which lies on the outer surface of the heart wall. The ganglion is regulated by one pair of cardioinhibitory nerves and two pairs of cardioacceleratory nerves. Cardiac acceleration accompanied activation of the five pairs of swimmerets in the first to the fifth abdominal segments. The cardioacceleratory nerves were activated when swimmerets beat strongly. Activation of the cardioacceleratory nerves was caused by electrical stimuli to a nerve branch extending to the swimmerets from the first nerve root of the abdominal ganglion. Bursts of afferent impulses were recorded from the nerve branch of the first nerve root corresponding to periods of protractive and retractive swimmeret movements. Afferent impulses were recorded from the nerve branch when the articular membrane was artificially boosted up. Cardiac acceleration during active swimmeret movements in Squilla is attributable to a reflexive response triggered by the movements. Putative mechanoproprioceptors on the articular membrane between the sterna and basipodite in the swimmerets may be responsible for the cardioacceleratory reflex.     

Synaptic transmission in the sixth ganglion of the cockroach: action of 4-aminopyridine.

1. Study was made of the action of 4-aminopyridine (5 X 10(-5) M) on synaptic transmission in the last abdominal ganglion of Periplaneta americana. The 'oil-gap' technique was used to record postsynaptic events in a single giant axon. 2. 4-AP quickly increased the 'background' of postsynaptic activity, which consisted of 'spontaneous' unitary EPSPs and IPSPs. Postsynaptic spikes were also propagated. 3. Both evoked EPSPs (stimulation of cercal nerve XI) and evoked IPSPs (stimulation of cercal nerve X) were greatly increased in amplitude although their duration (half-time) was unaltered. 4. 4-AP triggered presynaptic action potentials in the cercal nerves (recorded with external electrodes). These 'antidromic' potentials appeared singly or sometimes repetitively, especially after electrical stimulation of the cercal nerves. They were often in monosynaptic correlation with unitary EPSPs. 5. Neither the resting potential nor the postsynaptic membrane resistance was modified. 6. There were no changes in the equilibrium potentials of the ions involved in postsynaptic events. 7. The results may be essentially explained by an increase in transmitter release after 4-AP treatment, which may be partly the result of a rise in presynaptic terminal excitability, and partly the result of a lengthening of the presynaptic action potentials.     

Presynaptic uptake blockade hypothesis for LSD action at the lateral inhibitory synapse in Limulus

We investigated the action of LSD at the putative indoleaminergic lateral inhibitory synapse in the lateral eye of Limulus polyphemus. We recorded extracellular and intracellular voltage responses from eccentric cells while producing inhibition either by light or by antidromic stimulation of the optic nerve in the presence of LSD, serotonin (5-HT), chlorimipramine, or a bathing medium whose high Mg++ and low Ca++ concentrations partially or completely blocked synaptic transmission. We found (a) light-evoked and antidromically stimulated lateral inhibition is enhanced during superfusion of low (1-5 microM) concentrations of LSD and suppressed by higher (5-20 microM) concentrations; (b) these actions of LSD are markedly reduced by bathing the retina in a medium high in Mg++ and low in Ca++; (c) very low concentrations of chlorimipramine, a putative uptake blocker of serotonin, appear to mimic actions of LSD both on eccentric cell firing rate and on lateral inhibition; (d) superfused 5-HT depresses lateral inhibition at all superthreshold concentrations (0.1-25 microM). These results suggest that LSD's action may require an intact inhibitory transmitter release and postsynaptic response mechanism, whereas serotonin exerts a direct postsynaptic effect. We propose that LSD blocks presynaptic uptake of transmitter at the lateral inhibitory synapse. The concentration dependence of LSD's action can be accounted for as follows: low concentrations partially restrict transmitter reuptake, thereby prolonging the lifetime of the transmitter in the synaptic cleft and thus increasing the magnitude and duration of postsynaptic inhibition. Higher concentrations cause more presynaptic uptake sites to be blocked; this causes accumulation of transmitter in the synaptic cleft, which causes a functional blockade of the synapse because of postsynaptic desensitization. As an alternative, we propose a hypothesis based on LSD action at presynaptic autoreceptors. Similar hypotheses can account for many aspects of LSD's action in mammalian brain.     

Synaptic transmission in thoracic autonomic ganglia of the dog

Afferent stimulation of one canine thoracic cardiopulmonary nerve can generate compound action potentials in another ipsilateral cardiopulmonary nerve. These compound action potentials persist after acute decentralization of the middle cervical ganglion, indicating that they result from neural activity in the middle cervical ganglion and thoracic nerves. Changing the frequency of stimulation can alter the compound action potentials, suggesting that temporal facilitation or inhibition occurs in this middle cervical ganglion preparation. The compound action potentials can be modified by stimulation of sympathetic preganglionic fibers and by hexamethonium, atropine, phentolamine, propranolol, and (or) manganese. It thus appears that afferent cardiopulmonary nerves can activate efferent cardiopulmonary nerves via synaptic mechanisms in the stellate and middle cervical ganglia. It also appears that these mechanisms involve adrenergic and cholinergic receptors and are influenced by preganglionic sympathetic fibers arising from the cord.     

Developmental changes in dopamine modulation of the heart in the isopod crustacean Ligia exotica: reversal of chronotropic effect

Developmental changes in dopamine modulation of the heart were examined in the isopod crustacean Ligia exotica. The Ligia cardiac pacemaker is transferred from the myocardium to the cardiac ganglion during juvenile development and the heartbeat changes from myogenic to neurogenic. In the myogenic heart of early juveniles, dopamine affected the myocardium and caused a decrease in the frequency and an increase in the duration of the myocardial action potential, resulting in negative chronotropic (decrease in beat frequency) and positive inotropic (increase in contractile force) effects on the heart. Contrastingly, in the heart of immature adults just after juvenile development, dopamine caused effects of adult type, positive chronotropic and positive inotropic effects on the heart affecting the cardiac ganglion and myocardium. During the middle and late juvenile stages, dopamine caused individually a negative or a positive chronotropic effect on the heart. These results suggest that the chronotropic effect of dopamine on the Ligia heart is reversed from negative to positive in association with the cardiac pacemaker transfer from the myocardium to the cardiac ganglion during juvenile development.     

Electrophysiological investigation of the cat ciliary ganglion

Electrical responses of some nerves of the ciliary ganglion to stimulation of its other nerves were recorded, and intracellular recordings were also made from neurons of the ganglion (in situ). The overwhelming majority of preganglionic fibers terminate synaptically on neurons of the ganglion. Postganglionic fibers leave in the lateral and medial ciliary nerves, in which the velocity of conduction of excitation ranges from 1.9 to 9.0 m/sec. A few preganglionic fibers pass through the ciliary ganglion into the lateral ciliary nerve, giving off collaterals to neurons of the ganglion, so that stimulation of the lateral ciliary nerve evokes a response in the medial ciliary nerve (preganglionic axon reflex). The resting potential of neurons of the ciliary ganglion is 57±2.8 mV, and their action potential 68±3.6 mV. Single orthodromic stimulation usually evokes a single action potential in a neuron. The amplitude of the EPSP is increased during hyperpolarization of the postsynaptic membrane, confirming the chemical nature of synaptic transmission in the ganglion. The antidromic response consists of an IS-component and spike. The spike is followed by after-hyperpolarization, with a mean amplitude equal to 31% of the spike amplitude, and the time taken for it to fall to one–third of its initial amplitude is 75–135 msec.A. A. Bogomolets' Institute of Physiology, Academy of Sciences of the Ukrainian SSR, Kiev. Translated from Neirofiziologiya, Vol. 1, No. 1, pp. 101–108, July–August, 1969.     

Pre- and post-synaptic activity of glutamate on preparations of the frog semicircular canal

Glutamate (Glu) has at least two sites of action in the frog semicircular canal: the hair cell (presynaptic) and the primary afferent nerve fibres (postsynaptic). Glu's action on the hair cell results in an increased release of the natural transmitter which is responsible for a substantial increase in the frequency of firing in primary afferents. Glu produces a long-lasting depolarization in the afferent nerve fibres which does not by itself elicit any afferent discharge of impulses when the release of the natural transmitter is prevented. The difficulty of reconciling some of the observations made of the effects of Glu in semicircular canals with its presumed role as an afferent transmitter in this organ is discussed.     

Electrophysiological properties of neurons and neuronal organization of the crayfish somatogastric ganglion

Experiments with intracellular recording from neurons of the isolated crayfish somatogastric ganglion established that the membrane potential of the neurons is 53±3 mV. Single stimulation of the central branches of the ganglion evoked EPSP and a spike in the neurons. The spike amplitude was 7.5±0.6 mV. The small amplitude of the spike is explained by the fact that it arises at some distance from the body of the neuron and propagates electrotonically in it. Summation of several EPSP is necessary in most cases for initiation of the spike. When the orthodromic stimulus was strong enough, and IPSP occurred in some cells in addition to the EPSP and spike. Stimulation of the peripheral nerves of the ganglion induced in most neurons antidromic excitation and in some neurons orthodromic excitation. Some neurons spontaneously discharged rhythmically with an unstable frequency (11–27 impulses/sec). An investigation of the effect on neurons of chemical agents [acetylcholine, adrenalin, noradrenalin, gamma-aminobutyric acid (GABA), glutamic acid, and dopamine] showed that acetylcholine has the strongest and most stable depolarizing action and apparently is a synaptic transmitter in the ganglion. The other agents excited some neurons — depolarized them and evoked rhythmic discharges — and, coversely, hyperpolarized and suppressed the rhythmic activity of other neurons. A scheme of neuronal organization of the somatogastric ganglion of the crayfish is proposed.A. A. Bogomolets Institute of Physiology, Academy of Sciences of the Ukrainian SSR, Kiev. Translated from Neirofiziologiya, Vol. 2, No. 3, pp. 307–313, May–June, 1970.     

Cyclic Adenosine Monophosphate in the Nervous System of Aplysia californica : I. Increased synthesis in response to synaptic stimulation

In the isolated abdominal ganglion of Aplysia, previously incubated in adenine-³H, the amount of ³H-labeled adenosine-3',5' monophosphate (cAMP) doubled after electrical stimulation of nerves at a physiological rate (1/sec). No change was detected after 4 min of stimulation. An increase in cAMP was first seen after 15 min; lengthening the period of stimulation to 1 hr did not increase the extent of the effect. ATP contained 50% of the total radioactivity taken up from adenine-³H, cAMP about 0.1%. During stimulation both the total amount and the specific radioactivity of adenosine triphosphate (ATP) did not change. Thus, the increased amount of radioactivity found in cAMP after stimulation represented an increase in its rate of synthesis. During stimulation formation of cAMP-³H was not altered in nerves or in the cell body of an identified neuron (R2). In addition, no changes were detected in the total amounts of cAMP in the ganglion and in the cell body of R2. It seems likely that the increase was initiated by synaptic activity rather than by action potentials. It was blocked by elevating the concentration of Mg, which also blocks synaptic activity without impairing conduction of impulses. Moreover, impulse activity induced by ouabain and glutamate did not result in increased formation of cAMP.     

Kainic acid and synaptic transmission in the stellate ganglion of the squid.

Kainate, a conformational analogue of glutamate, blocks synaptic transmission across the giant synapse of the squid. In the presence of blocking doses of kainate, impulses continue to propagate into the nerve terminal, but action potentials are slightly reduced in size and the subsequent hyperpolarization is greatly diminished. Kainate depolarizes the postsynaptic axon. Since the depolarizing action of kainate is confined to the postsynaptic membrane, it appears that kainate can combine with the receptors which are normally activated by the transmitter. This results in a diminished effect of the transmitter released by a presynaptic nerve impulse.     

Physiology of Photoreceptor Neurons in the Abdominal Nerve Cord of the Crayfish

Nerve fibers which respond to illumination of the sixth abdominal ganglion were isolated by fine dissection from connectives at different levels in the abdominal nerve cord of the crayfish. Only a single photosensitive neuron is found in each connective; its morphological position and pattern of peripheral connections are quite constant from preparation to preparation. These cells are "primary" photoreceptor elements by the following criteria: (1) production of a graded depolarization upon illumination and (2) resetting of the sensory rhythm by interpolated antidromic impulses. They are also secondary interneurons integrating mechanical stimuli which originate from appendages of the tail. Volleys in ipsilateral afferent nerves produce short-latency graded excitatory postsynaptic potentials which initiate discharge of one or two impulses; there is also a higher threshold inhibitory pathway of longer latency and duration. Contralateral afferents mediate only inhibition. Both inhibitory pathways are effective against both spontaneous and evoked discharges. In the dark, spontaneous impulses arise at frequencies between 5 and 15 per second with fairly constant intervals if afferent roots are cut. Since this discharge rhythm is reset by antidromic or orthodromic impulses, it is concluded that an endogenous pacemaker potential is involved. It is postulated that the increase in discharge frequency caused by illumination increases the probability that an inhibitory signal of peripheral origin will be detected.     

Desipramine Binding: Relationship to Central and Sympathetic Noradrenergic Activity

We examined the effects of treatments affecting norepinephrine release on the number of norepinephrine reuptake recognition sites as reflected by desipramine binding. To do this, we used manipulations having similar presynaptic but contrasting postsynaptic effects. Presynaptic inhibition by 6-hydroxydopamine lesion or by clonidine, and postsynaptic receptor stimulation by isoproterenol, reduced desipramine binding. Presynaptic stimulation by d-amphetamine and postsynaptic receptor blockade by prazosin increased desipramine binding. Similar effects and binding properties were seen in cerebral cortex, heart, and soleus muscle. After unilateral noradrenergic lesions, reduction in desipramine binding correlated with reduction in norepinephrine uptake. These results show that norepinephrine reuptake appears to be regulated by transmitter release regardless of effects on postsynaptic transmission, and that this regulation is analogous in the central and sympathetic nervous systems.     

TRANSPORT OF NORADRENALINE IN SYMPATHETIC NERVES AND THE EFFECT OF NERVE IMPULSES ON ITS CONTRIBUTION TO TRANSMITTER STORES

Abstract— —A study has been made of the contribution of noradrenaline transport along sympathetic nerves to their terminal stores of transmitter by ligating the splenic nerves of the cat, and measuring both the noradrenaline that accumulates above the constriction, and the noradrenaline content of the spleen. The biochemical estimations were supplemented by fluorescence histochemistry. The effect of abolishing efferent impulses in the splenic nerves was examined by cutting their preganglionic nerve supply.
The proximo-distal flow rate for noradrenaline was calculated as 1.4-3.3 mm/hr assuming that all the noradrenaline that accumulates is derived from the cell bodies in the ganglion without net addition or loss in the axons. The process was not dependent on impulse traffic in the nerves, since decentralization did not significantly effect the accumulation. The amount of noradrenaline arrested by the constriction in 24 hr was only 1 per cent of the stores in the terminals of those nerves, and consequently no change was detected in the spleen's noradrenaline content as a result of constricting its nerve supply.
In the presence of an intact reflex pathway to the spleen, the stress of the operative procedure produced a marked constriction of the spleen, and depletion of its noradrenaline content. These changes could be prevented either by section of the preganglionic splanchnic nerves, or by ligation of the splenic nerves, thereby blocking the conduction of efferent nerve impulses.
The evidence favours a proximo-distal flow of noradrenaline in sympathetic nerves, independent of nerve impulses, which makes, however, a negligible quantitative contribution to the terminal stores of transmitter.     

Slow cardioacceleration mediated by noncholinergic transmission in the stellate ganglion of the cat

In C1-spinal, pentobarbital-anaesthetized or anemically decerebrated cats, the preganglionic input to the acutely decentralized right stellate ganglion was stimulated with 10- to 30-s strains at 20-40 Hz. Electrical stimulation consistently produced an increase in heart rate in the presence of blocking doses of hexamethonium and atropine or after depletion of acetylcholine from the preganglionic axons by prolonged low frequency stimulation in the presence of hemicholinium. The increase in heart rate had a delayed slow onset, lasted several minutes, and was abolished by propranolol or by section of the inferior cardiac nerve. The magnitude and duration of the heart rate increase were related to intensity, frequency, and duration of preganglionic stimulation. The response to stimulation of a given white ramus was progressively attenuated, and eventually irreversibly lost, during prolonged continuous stimulation of that ramus, while the response to stimulation of a different unstimulated ramus was unchanged. We conclude that the slow cardioacceleration results from a slow and prolonged excitation of postganglionic neurons by a noncholinergic transmitter released by the preganglionic axons.     

Quantal Mechanism of Transmitter Release during Progressive Depletion of the Presynaptic Stores at a Ganglionic Synapse : The action of hemicholinium-3 and thiamine deprivation

In the present experiments we interfered with the mechanism of acetylcholine (ACh) synthesis in the rat superior cervical ganglion by impairing the supply of either the choline group (hemicholinium no. 3 [HC-3]treatment) or the acetyl group (thiamine deprivation). Under both conditions stimulation causes in the ganglion a progressive decline in ACh output associated with a depletion of transmitter tissue content. ACh release from the terminals of a single preganglionic fiber was estimated from the quantum content value of the evoked excitatory postsynaptic potentials (EPSP's) recorded intracellularly in the ganglion neuron under test. The present observations indicate that Poisson statistics describe transmitter release at either low or high release levels. Furthermore, the progressive decline in the rate of ACh output occurring during repetitive stimulation is shown to correspond to a progressive decrease in the number of transmitter quanta released per impulse and not to any modification in the size of individual quanta. Some 8,000 transmitter quanta proved to represent the presynaptic transmitter store initially present in those terminals on a neuron that are activated by stimulation of a single preganglionic fiber. Speculations are considered about synaptic efficacy and nerve connections in rat autonomic ganglia. It is suggested that six preganglionic fibers represent the mean input to a ganglion neuron.     

Inhibitory Synapses on Pacemaker Neurons in the Heart Ganglion of a Stomatopod, Squilla oratoria

The pacemaker neurons of the Squilla heart ganglion are innervated from the CNS through three pairs of extrinsic nerves. One of them, the α-nerve, is inhibitory to the heart beat. The effect of α-nerve stimulation on the pacemaker potential was examined with intracellular electrodes. Without extrinsic nerve stimulation the membrane potential of the pacemaker cell fluctuated spontaneously. On application of a tetanic train of stimuli to the α-nerve the membrane potential was shifted and fixed to a steady level, which with K₂SO₄-filled electrodes was near the peak of hyperpolarization after a spontaneous burst, but was less negative with KCl-filled electrodes. The shift of the membrane potential was due to the summated IPSP's. By changing the level of the membrane potential with injection of the polarizing current the IPSP could be reversed in sign, and the size of the IPSP was linearly correlated with the membrane potential level. During inhibition the membrane conductance increased. The increase depended on divalent cation concentrations in the outside medium. In Ca-rich saline the IPSP was greatly enhanced. In Mg-rich saline it was suppressed. The amplitude of antidromic spikes was reduced during inhibition especially when the spike frequency was high.     

The Sites of Action of Pericardial Organ Extract and 5-Hydroxytryptamine in the Decapod Crustacean Heart

Responses of isolated, perfused hearts of Homarm americanusto brief, internal application of extracts of pericardial organs(PO's) ofCancer borealis, or 5-hydroxytryptamine (5HT) are verysimilar over a thousand-told range of concentration: an increasein rate and amplitude of beating. These reach their maxima afterwashing out has begun, and recover within ten minutes. Externalapplication is ineffective and the substances do not interactwith effects of stretch stimulation. Intracellular recordingfrom heart muscle fibers reveals facilitation of depolarizationto bursts at heart beat frequencies. There may be some effectof 5HT directly on neuromuscular facilitation. Responses recordedfrom isolated cardiac ganglia show increased burst rate, burstduration, or both. Thresholds and the range of concentrationsfor which coordinated responses are recorded correspond to thosefor perfused hearts. It is concluded that the major sites ofaction of PO extract and 5HT are in the cardiac ganglion. 5HTtachyphlaxis and LSD block effects of 5HT, but not of PO extractor accelerator nerve stimulation. Intracellular recordings fromthe large ganglion cells show no effects on resting, synaptic,or spike potentials. Changes in membrane potential to currentpulses revealed no changes in membrane resistance or in theresistance of the electrotonic pathway between cells. Resultsof selective application to large or small cells suggested thatPO extract may contain a rate-increasing substance and one prolongingthe duration of bursts. The former, and 5HT, may influence pacemakerpotentials; the latter may increase the number of spikes a unitcan produce before becoming refractory.