Cardiac Output and Blood Flow Distribution during Rest and Classical Aversive Conditioning in Monkey

Cardiac output was measured by dye dilution in rhesus monkeys (n = 9) during rest and classical aversive conditioning. A 1- min tone (followed by unavoidable electric shock) served as the conditional stimulus (CS +). Cardiac output was determined at approximately 30 sec before and after onset of CS +. Conditional increases in mean blood pressure (78± 11 to 84±11 mmHg. average±SD) and heart rate (145±23 to 166 ± 31/min) were associated with a significant (p<.01) increase in cardiac output (1.32 ± .25 to 1.69±.51 L/min) and decrease in total peripheral resistance (60.8 ± 13.7 to 53.1 ± 14.8 mmHg/L/min). There were no significant changes in these variables during a different tone (CS-) which was never followed by shock. Infusion of radio-labeled microspheres (5 monkeys) at 25-30 sec after CS + onset revealed a conditional increase (vs resting control) in flow to the diaphragm and certain other skeletal muscle; myocardial blood flow was not increased at this time. Flow decreased to the kidney, liver and pancreas. Elimination of the conditional increase in blood How to skeletal muscle following administration of propranolol (3 monkeys) suggests that the redistribution of cardiac output during “stress” may involve an active adrenergic vasodilation in the non-human primate.     

Elicitation of Subjective Uncertainty during Vasomotor and Electrodermal Discrimination Classical Conditioning

Subjective uncertainty was introduced during discrimination classical conditioning of the skin conductance and vasomotor responses. All 48 college student subjects were informed that one 7-sec colored light would always be followed by a shock (CS+) while a 7-sec light of another color would never be followed by a shock (CS?). After half of the conditioning trials, a novel stimulus (NS) was illuminated (a third color) and remained on. One group was previously informed about the NS while the other group was noninformed. Results of between trial verbal reports and postsession interviews indicated that noninformed subjects experienced more general uncertainty and more uncertainty regarding the CS-US contingency on the postNS trials than did the informed group. On the trial pair following the NS onset, the short latency electrodermal response (1 to 4.5 sec) of the noninformed subjects increased while the informed subjects maintained a stable level of responding. Evaluation of later postNS trials revealed that the long latency response (4.6 to 7.9 sec) of the noninformed subjects decreased more than for the informed subjects. The decrease for the noninformed subjects was greatest to CS+. No group differences in vasomotor activity were elicited by NS onset. It was concluded that momentary increases in orienting and more sustained decreases in preparatory activity may accompany increases in subjective uncertainty.     

Effects of lenticular stimulation on unitary and mass responses of the visual cortex to light

Summary Effects of lenticular stimulation on unitary and mass responses of the visual cortex were studied in acutely prepared cats. A conditioning shock applied to the lenticular nucleus (globus pallidus and putamen) resulted in an increase in amplitude of primary components of the photically evoked potential in the lateral gyrus. The increase in amplitude of the evoked potential was observed not only in the ipsilateral visual cortex but also in the contralateral one. Marked increase was noted at several conditioning-test intervals. Unitary responses of visual cortical cells to light were enhanced or inhibited by the conditioning shock to the lenticular nucleus. In units which fired primarily after flash, enhancement of firing was observed more commonly than inhibition, but in units which showed a primary neuronal silence after light, it was vice versa. It is concluded that the lenticular nucleus participates in the visual cortical activity.     

Selective impairment of Pavlovian conditional responses by electroconvulsive shock

Fourteen ewes were assigned to four Pavlovian conditioning paradigms: (1) one ewe received click conditional stimuli (CS) for 12 sec which was followed by a mild head-shock (MHS); (2) two ewes experienced the click CS followed by an electroconvulsive shock (ECS); (3) three ewes were conditioned under click CS-MHS as above, but each CS-MHS pairing was followed 1 min later by a second MHS; and, (4) ten ewes were subjected to the CS-MHS pairing followed 1 min later by ECS. Two conditioning trials were given every day for 12 days, one in the morning and one in the afternoon. In the CS-ECS conditioning paradigm, the ECS was ineffectual in establishing a motor CR, or other CRs, such as conditional EEG, heart rate, and blood pressure responses. When the ECS was given 1 min after each CS-MHS pairing, it significantly attenuated the motor CR, but did not interfere with acquisition of conditional EEG, heart rate and blood pressure responses. The occurrence of selective impairments in CRs confirmed the findings of Hine and Paolino [12].     

AVOIDANCE CONDITIONING OF THE GSR: NATURE OF THE RESPONSE

The effects of avoidance conditioning of the GSR on HR responses were investigated. Seven Ss were allowed to avoid a shock if their GSR during a preceding 5.0 sec light was greater than a criterion magnitude. Each avoidance S had a yoked-control partner who received exactly the same series of shocked and nonshocked trials, regardless of his own GSR behavior. Sixty trials were given. Avoidance Ss gave significantly larger GSRs and cardiac deceleration took place at a significantly greater rate in the avoidance group. The results were interpreted as supporting the conclusion that when an avoidance paradigm is used to modify a particular autonomic response, the effects extend to other autonomic arousal or anticipatory responses. Each S was questioned in a post-training interview about his awareness of means of avoiding the shock. No S was able to verbalize any method that could be used to prevent shock from occurring.     

Thrombocytopenia provoked by carrageenan in rabbits and the inhibitory effect of lysozyme

Hen egg white lysozyme (Fleming's lysozyme) prevented the thrombocytopenia provoked by carrageenan injected intravenously into rabbits but not that provoked by an anaphylactic shock. Lysozyme was given intravenously at 25, 50, 100 mg/kg 30 sec before carrageenan. Platelets were counted 15 and 60 min after carrageenan. Lysozyme was given intravenously to immunized animals at the dose of 100 mg/kg 5 min before a challenging dose of the antigens (horse serum-ovalbumin). Platelets were counted 5 min after challenge.The results are discussed in the light of the intervention of platelets and prostaglandins into tumour spread and metastases dissemination.     

Cardiovascular Changes During Classical Conditioning in the Squirrel Monkey

Changes in blood pressure (BP) and heart rate (HR) were classically conditioned in squirrel monkeys using light as the conditional stimulus, and electric shock as the unconditional stimulus. The transient (lasting less than 5 min) and sustained (maintained for a half-hour or more) changes in BP and HR in response to light-shock (LS) pairs and light alone (L) were measured while varying rates of presentation and shock intensity. LS presentation produced transient increases in both BP and HR. The magnitude of the change increased with shock intensity and decreased as stimulation rate increased. Transient changes in BP and HR in response to L presentation were induced by conditioning with LS. The conditioned transient response to L alone was greater when the LS conditioning period preceding it had greater shock intensity or slower presentation rate. Sustained changes in BP and HR were also produced by LS, the magnitude of which were directly related to the frequency of aversive stimulus presentation. Transient changes, in contrast, decreased in magnitude with more frequent presentation.     

Effects of CS Duration and Instructional Set on Cardiac Anticipatory Responses to Stress in Field Dependent and Independent Subjects

The study showed that within a modified delayed conditioning paradigm the shape of the anticipatory cardiac response to shock can be modified by changing the CS duration. When the tone (CS) duration was only 4 sec, there was a significant HR acceleration. With the CS duration increasing stepwise, from 4 to 12 sec, the anticipatory cardiac response to the UCS became biphasic. The acceleratory component of this response was bound to the CS and time locked, and, on the average, reached its peak within 5 sec after the onset of the CS. The deceleratory component was directly related to the length of the time interval between the onset of the CS and the UCS: there was no anticipatory deceleration when the tone duration was 4, 5, or 6 sec; the most pronounced deceleration was observed during the 10 sec interval. Instructional sets did not significantly affect cardiac activity by themselves, but did influence responses in interaction with the individual difference variable of field dependence; this was found to be the case only on the first trial. Field dependence was also a meaningful variable, and accounted for some of the differences in the patterns of HR responding in anticipation of shock.     

Stimulation-induced factors which affect augmentation and potentiation of trasmitter release at the neuromuscular junction.

1. End-plate potentials (e.p.p.s) were recorded from frog sartorius neuromuscular junctions under conditions of decreased transmitter release to study the effect of repetitive stimulation on augmentation and potentiation of transmitter release. 2. The magnitudes and time constants of decay of augmentation and potentiation were determined both following a primary conditioning train and following an identical secondary conditioning train applied from 30 to 170 sec after the primary conditioning train. 3. The magnitude of augmentation following the secondary conditioning trains was increased over that following the primary conditioning trains even though augmentation, with a time constant of decay of about 7 sec, had decayed to insignificant levels before the onset of the secondary trains. This increase in augmentation was not due to a change in its rate of decay during the secondary trains. 4. The increased magnitude of augmentation can be described as arising from an expression factor which, for conditioning trains of 200 impulses at 20/sec, has an initial magnitude of 1-6 +/- 1-2 (S.D. of observation) (the magnitude of augmentation is increased 2-6 times) and decays approximately exponentially with a time constant of 90 +/- 50 (S.D. of observation) sec. The expression factor thus decays about ten times slower than augmentation. 5. Doubling the number of impulses in the primary conditioning train from 100 to 200 led to a 2-8 +/- 1-0 (S.D. of observation) times increase in the magnitude of the expression factor, estimated by placing a 200 impulse secondary conditioning train 40 sec after the primary conditioning train. 6. The expression factor, while increasing the magnitude of augmentation, had little or no effect on the magnitude of potentiation or on trasmitter release in the absence of augmentation. The expression factor decayed about twice as slowly as potentiation. 7. The time constants characterizing the decay of potentiation were greater following the secondary conditioning trains than following the primary conditioning trains. 8. The increased time constant for the decay of potentiation can be described as arising from a time constant factor which, for conditioning trains of 200 impulses at 20/sec, has an initial magnitude of 1-2 +/- 0-7 (S.D. of observation) (the time constant of potentiation is increased 2-2 times) and decays approximately exponentially with a time constant of 130 +/- 45 (S.D. of observation) sec. The time constant factor decayed about three times slower than potentiation. 9. Doubling the number of impulses in the primary conditioning train from 100 to 200 led to a 1-6 +/- 0-8 (S.D. of observation) times increase in the magnitude of the time constant factor, estimated by placing a 200 impulse secondary conditioning train 40 sec after the primary conditioning train. 10...     

Avoidance conditioning in nine strains of inbred mice using optimal stimulus parameters

A total of 66 mice from nine highly inbred strains were tested on an avoidance conditioning task using optimal stimulus parameters derived from previous research. CS-US interval was set at 3 sec, intertrial interval at 120 sec, and shock at 400 v. These parameters were successful in differentiating strains, yielding a number of significant differences, with SWR/J the fastest-conditioning strain and BALB/cJ the slowest-conditioning strain.This research was supported by National Research Council of Canada Grant APB-105.     

Long-lasting potentiation of synaptic transmission in the dentate area of the anaesthetized rabbit following stimulation of the perforant path

1. The after-effects of repetitive stimulation of the perforant path fibres to the dentate area of the hippocampal formation have been examined with extracellular micro-electrodes in rabbits anaesthetized with urethane.2. In fifteen out of eighteen rabbits the population response recorded from granule cells in the dentate area to single perforant path volleys was potentiated for periods ranging from 30 min to 10 hr after one or more conditioning trains at 10-20/sec for 10-15 sec, or 100/sec for 3-4 sec.3. The population response was analysed in terms of three parameters: the amplitude of the population excitatory post-synaptic potential (e.p.s.p.), signalling the depolarization of the granule cells, and the amplitude and latency of the population spike, signalling the discharge of the granule cells.4. All three parameters were potentiated in 29% of the experiments; in other experiments in which long term changes occurred, potentiation was confined to one or two of the three parameters. A reduction in the latency of the population spike was the commonest sign of potentiation, occurring in 57% of all experiments. The amplitude of the population e.p.s.p. was increased in 43%, and of the population spike in 40%, of all experiments.5. During conditioning at 10-20/sec there was massive potentiation of the population spike (;frequency potentiation'). The spike was suppressed during stimulation at 100/sec. Both frequencies produced long-term potentiation.6. The results suggest that two independent mechanisms are responsible for long-lasting potentiation: (a) an increase in the efficiency of synaptic transmission at the perforant path synapses; (b) an increase in the excitability of the granule cell population.     

Sensitization of the acoustic startle reflex by footshock

Administration of footshock (500-ms duration, 0.2-1.4 mA) increased the amplitude of the startle reflex for a long time after its presentation. The effect occurred with a single footshock, although its magnitude and consistency across animals was greater with 5 or 10 footshocks presented 1/s. The facilitatory effect came on within 2-4 min with a 0.6-mA shock, peaking in about 10 min and then dissipating over the next 40 min. Stronger shocks also increased startle, but with a more delayed onset of facilitation (8-10 min). Footshocks increased startle in rats not previously given startle-eliciting stimuli, indicating sensitization rather than dishabituation. The facilitatory effect may not be attributable to a rapid conditioning to the experimental context, because a change in lighting conditions from shock presentation to testing did not attenuate shock sensitization. This excitatory effect of shock on startle may represent the unconditioned effect of shock that can become associated with a neutral stimulus to support classical fear conditioning.     

The relationship between electrodermal and digital vasomotor responses in aversive classical conditioning

Thirty-two subjects, exposed to a tone CS, shock UCS simple delayed conditioning paradigm with an interstimulus interval of 8 sec, were compared in skin conductance and finger pulse volume responses to a sensitization control group of 32 subjects given unpaired CS—UCS presentations. Magnitude, probability and amplitude of anticipatory and UCS omission responses were measured. Significant conditioning effects for both these types of response were observed using magnitude and probability measures of the two effector systems. Between-subject correlations showed significant positive relationships between vasomotor and electrodermal CS responses in the sensitization group and early in conditioning training. Later in training, however, this relationship disappeared, indicating a learned dissociation of the response systems during classical conditioning. Within-subject correlations showed that the two response systems developed quite independently over trials.     

Classical conditioning in the sea anemone, Cribrina xanthogrammica

Earlier attempts to classically condition sea anemones have yielded inconclusive results. Using light as CS and shock as US, conditioning as distinguished from sensitization and pseudoconditioning was demonstrated in anemones. Procedural controls included substitution of light alone, shock alone, and random light and shock in place of paired light-shock trials. Responses measured were electrical output and folding of the oral disc. The conditioned response was distinguished from the unconditioned response to light and the unconditioned response to shock in terms of response latency of both electrical and behavioral measures.     

Classical conditioning in the sea anemone, Cribrina xanthogrammica.

Earlier attempts to classically condition sea anemones have yielded inconclusive results. Using light as CS and shock as US, conditioning as distinguished from sensitization and pseudoconditioning was demonstrated in anemones. Procedural controls included substitution of light alone, shock alone, and random light and shock in place of paired light-shock trials. Responses measured were electrical output and folding of the oral disc. The conditioned response was distinguished from the unconditioned response to light and the unconditioned response to shock in terms of response latency of both electrical and behavioral measures.     

Human Pavlovian decelerative cardiac conditioning based on a respiratory-induced cardiac deceleration as an unconditional reflex.

This study was directed at examining the feasibility of using a respiratory-induced cardiac decelerative reflex as an unconditioned response (UCR) in a Pavlovian conditioning paradigm. Experiment I assessed the reflexive features of the cardiac response under a respiratory procedure which involved 3 sec of exhalation, 4 sec of inhalation, and then 30 sec of breath-holding (BH). The results indicated that the BH onset aspect of this respiratory cycle involved a phasic, large-magnitude cardiac deceleration (27 beats/min) with short latency, fast recruitment, and no indication of habituation over trials. Experiment II examined the feasibility of using BH onset as an unconditioned stimulus (UCS) in a Pavlovian paradigm by presenting an auditory conditional stimulus (CS) 1 sec prior to the instructed BH aspect of the respiratory cycle. A separate control condition involved presenting the CS 10 sec after BH onset which constituted a 'backward' conditioning control. The results indicated that the conditioning group displayed a significant cardiac deceleration on CS-alone test trials (under normal breathing) in contrast to the absence of such an effect for the control group. In brief, the study suggested that a decelerative conditioned response (CR) could be established by using a respiratory-induced cardiac deceleration as a Pavlovian UCS. Potential clinical applications of such a decelerative CR were noted.     

Graded acquisition of an instrumental avoidance response by the spinal rat.

Eight pairs of spinal rats were exposed to an instrumental conditioning paradigm in which one animal served as the experimental and the other as a yoked control animal. An electrode, inserted into the experimental animal's foot, contacted an aqueous solution delivering shock to both animals. Leg flexion terminated the shock. Following two consecutive min without shock, the experimental animal's solution was raised an additional millimeter and training was re-instated. This procedure was repeated 4 times, or until the experimental animal failed to reach the 2 min criterion. In Run 1, one leg was trained; during Run 2, the contralateral leg was used. In addition, the animal which served as the experimental in Run 1 served as the yoked control in Run 2 and vice versa. The results indicate that the spinal rat is capable of acquiring successively higher criteria in an instrumental conditioning routine. In conjunction with previous results, these findings suggest that instrumental avoidance learning can occur in the spinal cord.     

Retrograde amnesia induced by hypoxia and electroconvulsive shock in two rat strains.

Hypoxia or electroconvulsive shock (ECS) was administered to two strains of rats following one trial passive avoidance training. ECS produced retrograde amnesia in the Blue Spruce Farms Long Evans hooded rat when administered within 10 sec after training and in the Charles River albino rat when administered within 75 sec after training. Hypoxia was effective in producing retrograde amnesia when administered up to 40 min after training in the hooded rat but only when administered between 20 and 30 min after training in the albino rat. The importance of strain variability is discussed.     

Cardiovascular responses to acute footshock stress in adult and aged Fischer 344 male rats

Tail artery catheters were surgically implanted in Fischer 344 male rats to allow for measurement of mean arterial pressure (MAP, mm Hg) and heart rate (HR, beats/min) in conscious, unrestrained rats. Basal values of MAP and HR were similar for groups of 4, 12 and 24 month old rats. Increments in Map did not differ among rats of the 3 ages following handling and transfer to a shock chamber or immediately or 5 minutes after exposure to inescapable footshock (2.0 mA, 0.6 sec duration, every 6 sec for 1 min). In contrast, there was a significant age-related attenuation of the tachycardia following handling and transfer of rats to the shock chamber and at the end of footshock. These data are consistent with previous findings of a reduced sensitivity of the aged myocardium to stress-induced sympathetic stimulation.     

Reactivity to light and development of classical cardiac conditioning in the kitten

Kittens studied from 7 days onwards revealed that the earliest age at which cardiac conditioning can be established is 30 days, after some 30 light-electric shock associations. Older kittens showed both cardiac as well as motor conditioning. Animals younger than 21 days old had no well-defined cardiac responses to the clearly nociceptive unconditioned stimulus so that no cardiac conditioning was established; neither did they show signs of motor conditioning. This failure could be due to immaturity of the cardiac-emotional reactivity to nociceptive stimulation and immaturity of the neural structures involved in associative learning. Lack of reactivity to the light used as conditioned stimulus must be excluded because it already produced eye blink by 2 days of age. Moreover, a light-dark preference test done during the 1st postnatal week showed that kittens are able to discriminate light from dark by 8 days of age.