Excitatory Control Research Articles

Summation and transfer of negative occasion setting

Two experiments examined the summation and transfer of negative occasion setting in serial feature negative (X→A−/A+) and negative patterning discriminations (X→A−/X+/A+) in a discrete-trial operant task with rats. With both discrimination procedures, negative occasion setting transferred readily (but not perfectly) to cues trained as targets in another similar discrimination procedure, but not to cues that were separately trained. Furthermore, with both discrimination procedures, the negative occasion-setting powers of features from two individual discriminations summed, both when those features were trained with the same targets and when they were trained with different targets. After negative patterning discriminations, in which the feature (X) cues were separately reinforced, this summation of negative occasion setting occurred despite the concomitant summation of the features’ excitatory control in the absence of an explicit target cue. These data, which replicated and extended previously reported data from Pavlovian feature negative procedures, are discussed in the context of hierarchical, generalization, and network models of discrimination learning.

Differential modulation of striatonigral dynorphin and enkephalin by dopamine receptor subtypes

Previous studies indicate that dopaminergic transmission inhibits the biosynthesis of enkephalin and stimulates that of dynorphin in the striatonigral pathway of intact rat. The purpose of this study was to determine which dopamine (DA) receptor subtype(s) mediate the modulatory actions of DA. We measured striatal and nigral levels of enkephalin and dynorphin in: (1) intact rats repeatedly injected with D 1 (SKF-38393, 5 mg/kg, i.p.) or D 2 (LY-171555, 1 mg/kg, i.p.) agonists, alone or in combination, (2) 6-hydroxydopamine (6-OHDA)-lesioned rats repeatedly injected with the same D 1 or D 2 agonists, and (3) intact rats repeatedly injected with D 1 (SCH-23390, 0.05 mg/kg, s.c.) or D 2 (sulpiride, 100 mg/kg, s.c.) antagonists, given alone or in combination with the mixed D1/D2 agonist apomorphine (5 mg/kg, i.p.). Repeated injections of the D 1 agonist to intact rats (twice daily for 7 days) produced a small but not statistically significant increase in striatal levels of dynorphin; similar treatment with the D 2 agonist did not affect dynorphin levels at all. Combined treatments with D 1 and D 2 agonists did not potentiate the effect of the D 1 agonist. 6-OHDA lesions of the nigrostriatal DA pathway alone decreased the level of dynorphin in both the striatum and substantia nigra. However, repeated D 1 agonist, but not D 2, injections not only reversed the decrease in dynorphin levels, but caused a significant increase above control levels. In intact rats, repeated injections of the D 1 or D 2 antagonist alone failed to alter the levels of dynorphin, but the D 1 antagonist, not the D 2 antagonist, attenuated the apomorphine-induced increase in striatal dynorphin. Regulation of striatal [Met 5]enkephalin (ME) was found to be different from that of dynorphin. While repeated D 1 agonist injections in intact rats had no effect on striatal ME, D 2 agonist treatment caused a modest increase in ME. The effect of the D 2 agonist in intact rats was blocked by co-administration with the D 1 agonist. In addition, 6-OHDA lesions alone increased striatal levels of ME, and this increase was blocked by the D 1 agonist, but not the D 2 agonist. Finally, the D 1 antagonist increased the striatal level of ME in intact rats, whereas the D 2 antagonist had no effect. These data indicate that D 1 receptors mediate excitatory control over the biosynthesis of striatonigral dynorphin and also exert a tonic inhibitory influence on the enkephalin system. Furthermore, stimulation of the D 2 subtype imposes an excitatory stimulus on enkephalin biosynthesis but has no effect on dynorphin.

Effect of procaine injection into the ventromedial hypothalamic area (VMH) of the rat on serum insulin, glucose and corticosterone and gastric emptying rate

Bilateral injection of procaine into the VMH resulted in a decrease in serum glucose and immunoreactive insulin levels in both food-deprived rats and meal-fed rats. Corticosterone levels and gastric emptying rate were unaffected by these VMH procaine injections. Since it is likely that the procaine disrupted only those neurons whose cell bodies and synapses lay in the region of the VMH, the results suggest that the two major factors in the etiology of the ‘VMH syndrome’ following electrolytic lesions, rapid gastric emptying and insulin hyperresponsivity, are dependent upon destruction of fibers of passage through the VMH. Finally, the results further support the proposal that the VMH exerts tonic excitatory control over liver glucose output.

Control of gallbladder motility in the rainbow trout,Salmo gairdneri

Immunohistochemistry revealed nerves containing VIP-like and 5-HT-like material in both gallbladder wall and bile duct of the rainbow trout, while endocrine cells containing gastrin/CCK-like and substance P-like material were present in the mucosa of the bile duct and the duodenum. Fluorescence histochemistry showed adrenergic nerves close to the muscle layer of the gallbladder.Sulphated CCK8, caerulein and non-sulphated CCK8 (in this order of potency), 5-HT and acetylcholine were excitatory on isolated strip preparations, while VIP and adrenergic agonists were inhibitory. The adrenergic drugs were probably actingvia a beta-adrenergic receptor, while the effects of 5-HT and cholinergic drugs were antagonized by methysergide and atropine respectively.Electrical stimulation of the gallbladder nervesin situ failed to show any effect or under certain conditions induced a rebound effect.It is concluded that the motility control of the rainbow trout gallbladder may involve an inhibitory innervation by adrenergic and possibly VIP-releasing nerves, while 5-HT, acetylcholine and a CCK-like substance may be involved in the excitatory control.

Oral pressure receptors mediate a series of inhibitory and excitatory periods in the masseteric poststimulus EMG complex following tapping of a tooth in man

Poststimulus EMG complexes (PSECs), consisting of a series of inhibitory and excitatory waves in full-wave rectified and averaged electromyogram (EMG), were elicited in the masseter muscles of 7 subjects following controlled tapping of a tooth, at a controlled clenching level. Applying local anaesthesia to this tooth decreased the total surface of the waves, on average by 89%. The excitatory and the inhibitory waves were similarly affected, indicating that mainly pressure receptors in the periodontium mediate the entire PSEC. In 4 subjects, who were exposed to acoustic noise to exclude a contribution of acoustic receptors, the recovery of the PSEC waves from local anaesthesia was tracked. In 3 subjects, one wave (the first inhibitory or the first excitatory one, respectively) recovered differently from the other waves, indicating that they are not necessarily mediated by one type of afferent axons. The evidence, nevertheless, suggests that the different PSEC waves in man reflect the projection of the periodontal afferents upon several brain structures, involved in the control of the activity of the masseteric motorneurones, as: (1) inhibitory and excitatory control requires different groups of interneurones; and (2) a mediation of the first inhibitory wave by slower conducting axons than the second inhibitory wave, or a mediation of both waves by axons of similar type, is not compatible with common interneurones.

Influence of Renshaw cells on the response gain of hindlimb extensor muscles to sinusoidal labyrinth stimulation.

The contraction of limb extensor muscles during side-down roll tilt of the animal depends upon an increased discharge of excitatory vestibulospinal (VS) neurons (alpha-response) and a reduced discharge of inhibitory reticulospinal (RS) neurons of the medulla (beta-response), both acting on ipsilateral limb extensor motoneurons. In the decerebrate cat, a modulation of the multiunit EMG activity was clearly present in forelimb extensors, but was extremely weak or absent in hindlimb extensors. Experiments performed in decerebrate cats with the deefferented GS muscle fixed at a constant length have shown that Renshaw (R)-cells, monosynaptically coupled with gastrocnemius-soleus (GS) motoneurons, were either unresponsive or displayed only very weak, small amplitude alpha-responses to sinusoidal stimulation of labyrinth receptors elicited during slow head rotation after bilateral neck deafferentation. This effect was attributed to excitatory VS volleys acting on GS motoneurons and, through their recurrent collaterals, on the related R-cells. In these instances the recurrent inhibition of the GS motoneurons contributed to the very low gain of the EMG response of the corresponding muscles to labyrinth stimulation. Intravenous injection of an anticholinesterase (eserine sulphate, 0.05-0.1 mg/kg) at a dose that in previous experiments increased the firing rate of medullary RS neurons, while decreasing the decerebrate rigidity, slightly increased the discharge rate of R-cells linked with the GS motoneurons in the animal at rest; these findings suggest that the RS system inhibits the extensor motoneurons by exciting the related R-cells. All the R-cells, which prior to the injection were either unresponsive or showed an alpha-response to head rotation (at 0.026-0.15 Hz, +/- 10 degrees), after eserine sulphate showed a beta-response for the same parameters of labyrinth stimulation. In particular, a reduced discharge of the R-cells linked with the GS motoneurons occurred during side-down head rotation as shown for the majority of the RS neurons. It appears therefore that the same R-cells, which in the normal decerebrate cat responded to the excitatory VS volleys acting through the GS motoneurons, were now decoupled from their input motoneurons during head rotation, thus behaving as if they underwent the most efficient direct excitatory control of the RS system. The reduced discharge of the R-cells linked with the GS motoneurons during side-down head rotation would lead to disinhibition of these motoneurons, thus enhancing the response gain of the corresponding muscle to labyrinth stimulation.(ABSTRACT TRUNCATED AT 400 WORDS)

Do alpha-adrenergic mechanisms regulate spontaneous or opiate-modulated pulsatile luteinizing hormone secretion in man?

Brain noradrenergic mechanisms participate in the excitatory control of episodic LH release in many experimental animals, including the nonhuman primate. In addition, augmentation of pulsatile LH release in the rodent in response to opiate receptor antagonists is dependent upon intact central noradrenergic pathways. The applicability of these tenets to humans is not known. We tested the excitatory influence of brain noradrenergic systems on pulsatile LH secretion in normal men by administering phenoxybenzamine (an irreversible, preferentially postsynaptic, alpha 1-receptor blocker) or alpha-methyldopa (an inhibitor of brain adrenergic transmission). Five normal men underwent repetitive (every 20 min) venous sampling for 8 h to characterize episodic LH release quantitatively under basal conditions and after the administration of naltrexone, a potent opiate receptor antagonist which stimulates puslatile LH release. Subjects received saline, phenoxybenzamine (1 mg/kg, iv, over 90 min), or alpha-methyldopa (250 mg, orally, every 6 h). The following parameters of spontaneous episodic LH secretion were not altered after phenoxybenzamine or alpha-methyldopa administration: mean and integrated serum LH concentrations, LH pulse frequency, LH pulse amplitude (percentage or milliinternational units per ml increment), and absolute peak serum LH values. In addition, the administration of adrenergic inhibitors did not impede the capacity of naltrexone to significantly augment pulsatile LH secretion in these subjects. We conclude that in the doses used, phenoxybenzamine and alpha-methyldopa do not alter spontaneous or opiate-modulated episodic LH release in normal men.

Effects of question type and experimenter position on bilateral differences in electrodermal activity and conjugate lateral eye movements

28 dextral males participated in a within-subjects experiment which tasted for the effects of question type (verbal versus spatial) and experimenter-position (in front of or behind the subject) on direction of conjugate lateral eye movements (LEMs) and bilateral differences in skin conductance responses (SCRs). Question dependent asymmetries were observed for LEM direction but not for SCR magnitude. Experimenter-position had no significant effect. The results for LEM direction are consistent with the hypothesis linking eye movements to the left or right with activation of the cerebral hemisphere contralateral to the direction of gaze. The results for SCR magnitude, given certain assumptions, can be reconciled with a hemispheric model of contralateral excitatory control of that system.

Organization of the sympathetic innervation supplying the hairless skin of the cat's paw

The sympathetic outflow supplying the hairless skin of the cat's hind paw has been analyzed in brain-intact and chronic low spinal animals. For this purpose the activity of postganglionic axons in fascicles of the medial plantar nerve which innervate the central pad and the respective responses of the target organs (transient skin potentials, skin temperature) have been recorded. (1) Blood vessels and sweat glands in the hairless skin of the cat's hind paw are under efferent control of vasoconstrictor neurons, sudomotor neurons, and possibly vasodilatator neurons. (2) Vasoconstrictor neurons are largely under inhibitory control of various afferent input systems from the body surface and from the internal milieu, and sudomotor neurons under excitatory control in brain-intact as well as in chronic spinal cats. (3) The basic neuronal network or "machinery" for the this reciprocal organization is probably located in the spinal cord. (4) Effects of anesthetics on the sudomotor reflexes indicate that this spinal neuronal organization is controlled in a complex manner by descending spinal systems from the brain stem. (5) The existence of vasodilatator neurons, a third efferent control system supplying the hairless skin, which can only be activated by spinal cord warming in brain-intact as well as in chronic spinal cats is not very well established. Neurons with this property are rare and it is unclear whether they course through the sympathetic trunk or dorsal roots or through both. The axons of these neurons are unmyelinated. (6) The organization of the neuronal control of vessels and sweat glands in the hairless skin may be a paradigmatic model for studying the respective neuronal organization in the spinal cord and its descending control.

Constraints on Pavlovian aversive conditioning: Implications for avoidance learning in the rat

Four experiments investigated the relative degree of control exerted by several conditional stimuli when each stimulus: (a) preceded shock, (b) followed shock, and preceded a shock-free interval, (c) was independent of shock, or (d) was novel. When the onset of an auditory stimulus had preceded shock (Experiments 1, 2A, and 3), it always exerted conditioned excitatory control. When the same stimulus preceded a shock-free interval, it never exerted conditioned inhibitory control. When the onset of light (Experiments 2B, 4), silence (2C), or darkness (1, 2D) preceded a shock-free interval, it always exerted conditioned inhibitory control. However, when one of the latter stimuli preceded shock, it failed to exert excitatory control. Several models of this phenomenon were tested. The implications of these results for the species-specific defence reaction and two-factor theory accounts of avoidance learning were outlined.

Some pathophysiological aspects of spasticity and the search for rational and successful therapy.

In spite of the different uses of the term "spasticity", hyperactivity of skeletal muscle stretch reflexes is the one common factor and we therefore need to know how this is produced by lesions within the central nervous system and what are its consequences to the initiation and execution of voluntary movement, not only initially but also chronically. The alpha motoneurone is directly responsible for the initiation of skeletal muscle contraction and final integration of excitatory and inhibitory nervous input normally takes place on its surface. In spasticity there is not only loss of descending direct excitatory and inhibitory control of motoneurones, but also loss of the control of spinal interneurones which would normally regulate (principally by inhibition) segmental spinal reflexes, including the stretch reflexes, especially those concerned with antigravity muscles. Gamma motoneurones may also have a reduction inhibitory control with consequent increase of muscle spindle sensitivity to stretch, and this may be further exaggerated by changes in the physical properties of affected muscles. The peripheral disorders of function are more accessible to study and to pharmacological and physical treatment, but with the increasing knowledge of inhibitory mechanisms and their pharmacology there is hope that some degree of influence may be possible within the central nervous system, by therapy with drugs that mimic or prolong the action of inhibitory transmitters.

Disordered inhibition in internuclear ophthalmoplegia: analysis of eye movement recordings with computer simulations.

High resolution infra-red oculographic recordings were obtained in 19 patients with clinically evident internuclear ophthalmoplegia. The major findings were attenuated phasic and tonic components of adducting saccades, fractionated phasic components of abducting saccades, equally long durations for phasic components of adducting and abducting saccades with refixation, and nasal drift of the abducting eye which initiated abducting nystagmus. Ipsilateral gaze paresis and abduction lag were occasionally associated with primarily unilateral cases of internuclear ophthalmoplegia. These findings were interpreted using available anatomical, electromyographic and oculographic data as well as computer simulations of internuclear ophthalmoplegia. We concluded that deficient excitation of the ipsilateral medial rectus was due to interruption of burst-tonic neurons within the medial longitudinal fasciculus which mediate horizontal eye movements. This resulted in a decreased pulse height and step of the agonist neural controller signal. We were also able to determine that variably slowed fractionated abducting saccades were caused by deficient intrasaccadic inhibition of the antagonist medial rectus. When medial rectus excitation was more deficient than medial rectus inhibition of the opposite eye, then a typical internuclear ophthalmoplegia resulted; when the amount of medial rectus excitation was equal to the amount of medial rectus inhibition of the opposite eye, then a gaze paresis occurred; and when medial rectus excitation was less deficiennt than medial rectus inhibition of the opposite eye, abduction lag resulted in the oculographic appearance of internuclear ophthalmoplegia of abduction. Abducting nystagmus appeared to be initiated by a tendency for the abducted eye to drift nasally from the increased level of tonic inhibition of the antagonist medial rectus. Some oculographic patterns were attributed to higher level adaptive changes in innervation. These changes were a consequence of disordered excitatory and inhibitory controller signals at the lower, internuclear level. Possible anatomical pathways which might carry these inhibitory controller signals were discussed. High resolution eye movement recordings of patients with internuclear ophthalmoplegia were interpreted directly and by computer simulations as being most consistent with disordered inhibitory and excitatory control of the medial rectus motor pool during rapid eye movements and eccentric gaze.

Truly Random Control Group in Pavlovian Conditioning of Planaria (Dugesia Dorotocephala)

Both Jensen (1965) and Dyal (1973) have called for the introduction of the truly random control group in studies of planaria to provide an appropriate baseline against which to evaluate the associative effects of CS-US pairings. Accordingly, an experiment was performed comparing a Pavlovian excitatory conditioning group both with the traditional unpaired control group and a Rescorla truly random group. Three conditions were compared (six planaria in each) using a trace conditioning procedure (3-sec. light CS followed by a 1-sec. shock US). The major results of the experiment were that (a) the Pavlovian excitatory group showed an increase in performance only for the contraction CR measure, (b) head turns and combined CR measures showed only decreases or no changes in performance in any of the groups; (c) the performance of the truly random control group was between the Pavlovian excitatory and unpaired control groups, providing support for the notion that the latter is not truly a control condition but an inhibitory one.

Summation of excitatory and inhibitory control produced by traditional tone-shock contingencies and autocontingencies

Previous research has demonstrated that rats can be unsignaled shock to predict subsequent periods free from shock. This shock-no shock stimulus arrangement, termed an autocontingency, has appeared less likely to exert behavioral control when a traditional tone-shock contingency was simultaneously available. The present research examined the generality of CS-US contingency dominance in a conditioned suppression paradigm by using a summation test in which "probe" stimuli derived from tone-shock contingencies were superimposed upon responding maintained by an autocontingency. In experiment 1, an inhibitory CS accelerated responding only when responding was normally suppressed by the autocontingency. In experiment 2, an excitatory CS failed to yield conditioned suppression during an inhibitory (accelerative) period produced by the autocontingency. Unlike our previous findings (e.g., Davis, Memmott & Hurwitz, 1975), these results do not support a general notion of tone-shock contingency dominance over autocontingencies. Behavioral control by autocontingencies appears robust and "holds its own" in summation with both excitatory and inhibitory CSs derived from traditional contingencies.

Effects of the cilioexcitatory neurohumors dopamine and 5-hydroxytryptamine on cyclic AMP levels in the gill of the mussel mytilus edulis

Cyclic 3′, 5′-adenosine monophosphate (cAMP) has been identified in the ciliated gill epithelium of the marine mussel Mytilus edulis . In concentrations which stimulate the rate of particle transport by frontal gill cilia, DA and 5HT stimulate levels of cAMP within the gill. The stimulation occurs in as early as 15 sec and is graded from 10 −6M to 10 −4M. DA plus 5HT is not additive at maximal effective concentrations of both amines. ACH does not mimic the DA or 5HT stimulation of cAMP. Theophylline alone has a weak effect on cAMP levels; however, the effect of theophylline is potentiated in the presence of DA or 5HT. Dibutyryl cAMP produces a gradual stimulation in the rate of particle transport. It is suggested that the dopaminergic and serotonergic excitatory control of particle transport by frontal gill cilia of Mytilus edulis is mediated through a cAMP second messenger system.

Attention in the pigeon: testing for excitatory and inhibitory control by the weak elements.

In two experiments, pigeons were trained on a successive discrimination between a color and either a compound S+ or a compound S- consisting of a form superimposed on a second color. Two stimulus control tests followed discrimination training: an attention test in which the form and colors used in training were presented singly and in combination, and then a resistance-to-reinforcement test using the form element of S+ or S- and a novel form. In the attention test, the birds trained with a compound S+ responded most to the S+ compound, less to the S+ color alone, and still less to the S+ form on a dark key. Few responses were made to the negative stimulus, either alone or with the S+ form added. The birds trained with a compound S- pecked most at the S+ color and to a compound of the S+ color with the S- form added. The resistance-to-reinforcement test showed that the birds trained with a compound S+ responded more to the S+ form than to a novel form. However, the birds trained with a compound S- did not reliably respond more to a novel form than to the S- form. These findings suggested that the form element of a compound S+ gains some excitatory control, but the form element of a compound S- does not acquire inhibitory control. The possibility existed that low levels of responding to the S+ form on a dark background in the first experiment were due to use of a darkened key to separate S+ and S- periods during discrimination training. However, the essential findings were the same in a second experiment in which darkening of the chamber separated S+ and S- periods.

Stimulus generalization following extradimensional and intradimensional training in educable retarded children

Five related experiments investigating stimulus generalization following go/no-go discrimination training of educable retarded children are reported. Experiment 1 employed an Extradimensional paradigm in which generalization testing was on the hue dimension following training on an independent (orientation) dimension. Following True discrimination training only 25% of children showed a decremental stimulus generalization gradient on the hue dimension, though all children exhibited flat gradients in Pseudodiscrimination and S+ only control groups. An increase in difficulty of the orientation discrimination in Experiment 2 did not increase the number of decremental gradients. In Experiment 3, children who exhibited decremental gradients in Experiments 1 and 2 underwent further generalization testing with modified stimuli to establish a symmetrical gradient peaked at a hue S+ to be employed in Experiments 4 and 5. In these experiments an Intradimensional paradigm was employed with S+ and S− stimuli drawn from the hue dimension. Excitatory control by S+ and inhibitory control by S− were demonstrated, as were inhibitory consequences of S− such as peak and area shift.

Signalled Reinforcement and Dimensional Stimulus Control

Summary For four pigeons reinforcement was signalled in one component of a multiple variable-interval 1-min variable-interval 1-min schedule, and two pigeons were trained on a multiple variable-interval 1-min extinction schedule. Following training each bird was given a resistance-to-extinction generalization test, followed by an additional training session, and a final resistance-to-reinforcement generalization test. Test stimuli were combined with presence or absence of the signal. Generalization tests uniformly showed differential dimensional stimulus control in the presence and absence of the signal for three of the four signalled-reinforcement subjects. However, excitatory dimension stimulus control was obtained for the one signalled-reinforcement bird that did not respond differentially during training. Similarly, nondifferential, flat, or inhibitory gradients were obtained for the two extinction subjects. These data support an analysis of signalled reinforcement as a conditional discrimination.

Orogastric, hydrational, and behavioral controls of drinking following water deprivation in rats.

Drinking and its associated behaviors were studied in rats deprived of fluid for 8,24, or 48 hr. The behavior of rats drinking water could be divided into three successive stages: (a) an initial intense burst of drinking that could not be easily disrupted; (b) intermittent drinking, often distinguished by the brief appearance of conflict behavior directed at the drinking spout; and (c) termination of drinking. Drinking stopped well before the fluid loss, reflected in a sizable extracellular deficit, was restored. Intake of water was terminated when serum hyponatremia and hypoosmolality (and presumably cellular overhydration) developed in temporal continguity with drinking. These and other considerations suggest that the cellular fluid phase exerts significant inhibitory as well as excitatory control over drinking.

Acquisition of a temperature discrimination in neonatal dogs

Neonatal dogs were trained on a go, no-go discrimination task using thermal cues and were tested subsequently for inhibitory control. Stable differential responding was obtained but more training was required, and no-go performance was poorer in comparison to previous results on a tactile discrimination. The test trials suggest that the go, no-go behavior was only under differential excitatory control of the thermal cues.