Conditioning In Rabbits Research Articles

Classical conditioning of rabbits 2-1/2 to 4 years old using mossy fiber stimulation as a CS

A basic issue in age-related deterioration in memory formation concerns the locus of the age changes. Changes in peripheral portions of the auditory CS pathway could account for the observed age differences in classical conditioning in rabbits. We bypassed peripheral portions of the CS pathway and input the CS more centrally by electrical microstimulation of mossy fibers in the pons. New Zealand White rabbits aged 2-1/2-4 years were compared to six 3-month-old control rabbits with electrode implantations in comparable areas. Training consisted of 108 trials per day in which stimulation CS was paired with a corneal airpuff US. Older rabbits took almost five times as long to condition as the young animals. Thus, age differences in eyelid classical conditioning cannot be entirely attributed to changes in the peripheral CS pathway. Changes in the nervous system occurring more centrally in the cerebellum appear to affect learning and memory.

Hippocampal control of cingulate cortical and anterior thalamic information processing during learning in rabbits.

Past studies of the neural determinants of discriminative avoidance conditioning in rabbits have fostered a theoretical model that describes the interactive functioning of the cingulate cortex (Brodmann's Areas 24 and 29), the anterior ventral and medial dorsal thalamic nuclei (AVN and MDN) and the hippocampus. Here we test hypotheses of the model concerning the influence of the hippocampus on cortical and thalamic information processing. The rabbits learned to perform locomotory conditioned responses (CRs) in an activity wheel in response to an acoustic (pure tone) positive conditional stimulus (CS+). A shock unconditional stimulus (US) was given 5 s after CS+ onset, but locomotion during the CS+ - US interval prevented the US. The rabbits also learned to ignore a second tone (a negative conditional stimulus, CS-) of different auditory frequency than the CS+, that did not predict the US. Multi-unit activity and intracranial macropotentials were recorded in the cingulate cortex and the AVN during acquisition, overtraining, extinction, reacquisition and reversal training. Data were obtained in intact rabbits and in rabbits with bilateral lesions of the subicular complex, the origin of projections of the hippocampal formation to the cingulate cortex and AVN. In addition, the activity in the AVN was recorded in a separate group of rabbits with posterior cingulate cortical (Area 29) lesions. Subicular and Area 29 lesions were associated with an enhancement of the training-induced CS+ elicited neuronal response in the AVN. The frequency of CRs was enhanced in animals with subicular lesions. CS elicited unit responses in the cingulate cortices were attenuated in rabbits with subicular lesions. Both of the lesions were associated with significantly increased amplitudes of the CS elicited average cortical and thalamic macropotentials. These results suggested the following conclusions: subiculocortical afferents provide an enabling influence that is essential for CS elicited excitation in the cingulate cortex; the cingulate cortical excitatory response in intact animals exerts a limiting influence on the activity in the AVN; the enhanced AVN neuronal response in rabbits with lesions is due to the absence of the limiting influence and it contributes to the increased CR frequency in those animals. It is hypothesized that the hippocampus via subiculocortical projections, governs the flow of CR-inducing thalamocortical excitatory volleys. This governance determines the timing of CR output. The results of hippocampal processing of contextual information acting through the subiculocortical projection determines the moment most appropriate for the CR.

Initial localization of the acoustic conditioned stimulus projection system to the cerebellum essential for classical eyelid conditioning.

Previous experiments have demonstrated a sufficient and necessary involvement of mossy fibers in projecting conditioned stimulus information to the cerebellum during classical eyelid conditioning in rabbits. Presented here are electrophysiological, anatomical, and lesion data that suggest that cells within the lateral pontine nuclear region may be essentially involved in projecting information concerning the occurrence of acoustic conditioned stimuli to the cerebellum during classical conditioning.

Posterior cingulate cortical lesions eliminate learning-related unit activity in the anterior cingulate cortex

The frequency of multi-unit neuronal firing in response to tonal conditional stimuli increases, and the neuronal responses become discriminative in character, in the anterior and posterior subfields of the cingulate cortex (Brodmann's Area 24 and 29, respectively) during the course of discriminative avoidance conditioning in rabbits. Bilateral electrolytic lesions of the dorsal subicular complex eliminated the training-induced excitatory response in both cortical subfields, suggesting that subiculocortical projection fibers are essential for this effect. Yet, available data indicate that the subicular projection reaches only Area 29, not Area 24. Here we test the hypothesis that the subicular influence attains Area 24 via a synaptic relay in Area 29. The results showed in keeping with the hypothesis, that bilateral aspirative or electrolytic lesions in Area 29 eliminated the training-induced neuronal responses in Area 24. As in the case of subicular lesions, the Area 29 lesions increased the amplitude of the macropotentials in Area 24. These results are discussed in relation to a model of the interactions of the cingulate cortex, hippocampus and the limbic thalamic nuclei during learning.

The role of the medial geniculate region in differential Pavlovian conditioning of bradycardia in rabbits

The present study examined the role of the medial geniculate region (MGN) in differential Pavlovian conditioning of bradycardia and corneo-retinal potential (CRP) to acoustic stimuli in rabbits. Injections of horseradish peroxidase into the amygdala central nucleus, an area that mediates the bradycardia-conditioned reponse (CR), produced cell body and fiber labeling at the ventral and medial borders of the MGN. Then, bilateral electrolytic lesions were made at the medial border of the MGN or in control sites dorsal and/or rostral to the MGN. Ten days after surgery, lesioned and unoperated control animals were subjected to 7 days of differential Pavlovian conditioning. In the control lesion and unoperated groups, the CS+ consistently elicited larger bradycardia responses than the CS−. However, animals with bilateral lesions in the medial MGN did not demonstrate differential bradycardia CRs. Bradycardia response magnitude in MGN lesion animals was not affected. Evidence of CRP differential conditioning was present in each group. The present findings suggest that a region just medial to the MGN is involved in bradycardia differential conditioning in rabbits. The fact that bradycardia responses were still present after medial MGN lesions suggests that other auditory regions may also be involved in the mediation of the bradycardia CR.

Brain stem reticular formation neuronal correlates of stimulus significance and behavior during discriminative avoidance conditioning in rabbits.

Brain stem reticular formation neuronal correlates of stimulus significance and behavior during discriminative avoidance conditioning in rabbits.

Odor-related bulbar EEG spatial pattern analysis during appetitive conditioning in rabbits.

Mildly thirsty rabbits were classically conditioned by reinforcement with water to give a discriminative licking response to the presentation of odors. The jaw movement component of the licking conditioned response (JM CR) was elicited only by the reinforced odor; an increase in the relative frequency of sniffing (RR CR) occurred to both reinforced (CS+) and nonreinforced (CS-) odors. Oscillatory electroencephalographic bursts of high-frequency (40-80 Hz) potentials were recorded epidurally from the lateral olfactory bulb with 64-electrode arrays (8 X 8, 3.5 X 3.5 mm) chronically implanted. Emphasis was on comparing bursts during odor presentation with bursts preceding odor arrival on each trial. A "detection" burst was characterized as occurring immediately after odor arrival and before the sniff response. "Discrimination" bursts occurred during the RR CR and before the JM CR onset. Significant air-odor burst differences (together with sniffing) occurred through up to six sessions for both CS+ and CS- odors for "discrimination" bursts but not for "detection" bursts.

Odor-related bulbar EEG spatial pattern analysis during appetitive conditioning in rabbits.

Odor-related bulbar EEG spatial pattern analysis during appetitive conditioning in rabbits.

Crystal accumulation and very high short-circuit currents in rabbit urinary bladder.

We describe a condition in rabbits characterized by CaCO3 crystal accumulation and very high short-circuit current (Isc) in the urinary bladder. The incidence of the condition was high in rabbits kept for 2 mo or more in the vivarium. The crystal mass in the bladder increased with age or time until it occupied up to one-third of the bladder volume and occasionally aggregated as stones, and the urine attained a sludgy consistency. In animals with sludgy urine, the urine excreted had a crystal content 20 times lower than that of urine contained in the bladder at time of death, implying retention of crystals in the bladder. Kidney stones were not detected in rabbits with bladder crystals, and bladder crystals were absent in rabbits with kidney stones induced experimentally by uremia. In old rabbits with sludgy urine the Isc, a measure of Na+ transport, was up to 46 microA/cm2 and averaged 12 microA/cm2, seven times the Isc of rabbits with nonsludgy urine. The increased Isc was entirely amiloride sensitive. Noise analysis showed it to arise entirely from increased channel density, without change in single-channel current. With one possible exception, we could not find bacterial infection or abnormalities in plasma aldosterone, GFR, or urinary [Na+], [Ca2+], pH, or osmolality that could explain the condition. The exception is that some unidentified component accounting for half the osmolality of nonsludgy urine is absent or at low concentration in sludgy urine. It remains unknown why the condition develops and whether CaCO3 crystals cause high Isc or vice versa or whether both result from a third factor.

Increased responsivity of dentate granule cells during nictitating membrane response conditioning in rabbit

We examined the responsivity of dentate gyrus granule cells to perforant path stimulation during classical conditioning of the rabbit nictitating membrane response. Dentate field potentials elicited by perforant path stimulation were recorded during training to test for changes in granule cell responsivity. Results showed above-baseline increases in dentate population spike amplitudes over the course of training in paired but not unpaired animals. In addition, population spike amplitudes were smaller when elicited during tone presentations in both paired and unpaired animals than between trials when no conditioning stimuli were present. While alternative interpretations remain, these results provide preliminary evidence that processes similar to long-term potentiation may occur in the hippocampus during behavioral conditioning.

Naloxone induces multiple effects on aversive Pavlovian conditioning in rabbits.

A series of experiments examined the effects of intravenous naloxone treatment on aversive Pavlovian conditioning of eye-blink and heart rate responses, and related unconditioned behaviors, in rabbits. Naloxone treatment before testing attenuated bradycardiac orienting responses to tones used as conditioning stimuli. Naloxone also attenuated conditioned bradycardia when administered either before or after training sessions, but it potentiated conditioned bradycardia during extinction of discriminative conditioning. Naloxone did not influence acquisition or extinction of discriminative eye-blink conditioning or somatic or cardiac responses to shocks used as unconditioned stimuli, but it did decrease locomotor activity. Naloxone treatment immediately after training sessions facilitated acquisition of eye-blink responses. It was concluded that naloxone influences aversive Pavlovian conditioning in more than one way: (a) During training, it appears to alter reception and processing of signals but does not affect subsequent development of somatic responses to the Pavlovian conditioning contingency. (b) After training sessions, naloxone apparently affects consolidation of both somatic and autonomic conditioning. (c) Naloxone also appears to delay extinction of Pavlovian conditioning; this effect may similarly involve changes in a stimulus-processing mechanism or in memory functions, but it apparently does not involve changes in somatomotor responsitivity.

Naloxone induces multiple effects on aversive Pavlovian conditioning in rabbits.

Naloxone induces multiple effects on aversive Pavlovian conditioning in rabbits.

On-line detection of respiratory events applied to behavioral conditioning in rabbits.

The respiratory behavior of rabbits was analyzed to determine statistical features characteristic of exploratory sniffing. Statistical procedures and performance measures were incorporated into an on-line computer test to detect sniffing. The algorithm was employed in behavioral research to detect respiratory responses to conditioning stimuli in rabbits. The algorithm correctly sorted respiratory events from nonevents with an accuracy of 98 percent when compared to visual classification of polygraph tracings.

Correlation between EEG changes in the cortex, thalamus, and mesencephalic reticular formation during defensive conditioning in rabbits.

Correlation between EEG changes in the cortex, thalamus, and mesencephalic reticular formation during defensive conditioning in rabbits.

Effect of anodal polarization of deep brain structures on spatial synchronization of cortical potentials during defensive conditioning in rabbits.

1. Reversible blocking of some nonspecific thalamic and hypothalamic nuclei differs in its effect on two types of spatial synchronization of cortical potentials (SSCP) formed during defensive conditioned reflex (DCR) formation: Specific local SSCP and conditionedreflex movements disappear, whereas global SSCP remains virtually unchanged under these circumstances in interstimulus periods. 2. By modifying their functional state of these nuclei by anodal polarization it is possible to influence the rate of DCR formation. The effect of polarization depends on the structure to be stimulated and the stage of reflex formation. 3. During temporary blocking of hypothalamic nuclei phasic changes arise in local SSCP, which was never observed after blocking the nonspecific thalamic nuclei. 4. During reversible blockade of subcortical structures synchronization of cortical and subcortical potentials is depressed first. Conditioned-reflex movements appear only when synchronization between cortex and subcortex is recovered. 5. The conclusion can be drawn from the results that the mammillary bodies play an important role in the formation of local SSCP at the beginning of DCR formation and that the nonspecific thalamic nuclei and the posterior hypothalamic nucleus are essential for this form of spatial synchronization to arise on stabilization of the reflex, when definite correlation is observed between the appearance of local, specific SSCP, realization of the reflex, and strengthening of synchronization between the cortex and subcortical formations.

Studies of the decline of uteroglobin synthesis and secretion in the rabbit uterus during the continued presence of circulating progesterone.

To understand the physiology of the decline of uterine luminal uteroglobin content under various hormonal conditions in rabbits, the in vivo incorporation of 3H-labeled amino acids into uteroglobin was studied in pregnant, pseudopregnant, and progesterone-treated ovariectomized rabbits. The incorporation of 3H-labeled amino acids into the uteroglobin of progesterone-treated animals increased to days 4 and 5 and returned to low values by day 10. The uteroglobin content (in milligrams) of the uterine lumen was greater on day 5 in ovariectomized progesterone-treated (mean ± SEM, 1.70 ± 0.20), pseudopregnant (3.0 ± 0.75), and pregnant (1.6 ± 0.40) rabbits than on day 10 (0.6 ± 0.10, 0.9 ± 0.30, and 0.2 ± 0.1, respectively), and on day 10, the uteroglobin content was higher in the progesterone-treated and pseudopregnant animals than in the day 10 pregnant animals. In all three groups, the 3H-labeled amino acid incorporation into uteroglobin was much greater on day 5 than on day 10. The specific activities of a...

Correlation between the EEG and cortical unit activity during defensive conditioning

1. The relative proportion of neurons whose discharge correlates significantly with a certain configuration of EEG wave remains unchanged compared with the control during defensive conditioning in rabbits. 2. Values of integral coefficients of cross-correlation between the EEG and cortical unit activity in animals with an established conditioned reflex do not differ significantly from those in control animals. 3. In the course of 6–10 days of conditioning the amplitudes of both the positive and the negative EEG waves linked with unit discharges are reduced. 4. During defensive conditioning a short (under 20 msec) surface-positive wave of the combined potential, regularly linked with cell discharges, could be distinguished. This short wave is identified with the EEG quantum.

Changes in the cortical slow potential and unit activity during conditioning in rabbits.

1. In experiments on waking, unimmobilized rabbits changes in the slow potential and unit activity of the auditory cortex were compared during the first appearances of the reflex to acoustic stimulation and in the stage of its deep stabilization. 2. Diffuse generalization of excitation, the electrographic expression of which is the slow negative potential arising in response to the conditioned stimulus on the first appearances of the reflex, was shown to correlate at the cellular level with the formation of polysensory activity of the neuron and a small increase in the duration of its AP. 3. The stage of deep stabilization, specialization, and automation of the reflex is characterized by suppression of the initial diffuse, uneconomic excitation of centers, and the reflex is effected by a limited number of them. The appearance of the SPP in response to the conditioned stimulus indicates that it is produced without the active participation of the cortical representation of the conditioned stimulus. At the cellular level this corresponds to a switch by the neuron from the volley type of discharge to single rhythmic discharges.

Classical-classical transfer: Effects of prior appetitive conditioning upon aversive conditioning in rabbits

An appetitive-ayersive transfer experiment with rabbits determined that prior paired and unpaired tone CS and water US presentations, given in jaw-movement (JM) conditioning, respectively facilitated and retarded the acquisition of the nictitating membrane (NM) CR when the tone was subsequently paired with a shock US. In addition, the unpaired tone and water deliveries reduced the level of JM conditioning that was undertaken following the completion of NM CR acquisition. Finally, the reacquisition of the NM CR was accompanied by a large savings effect in contrast to the failure of the JM CR to display reacquisition savings. When the present findings are compared to the results of previous work addressing the influence of prior NM conditioning procedures upon subsequent JM CR acquisition, an asymmetry in appetitive-aversive interactions is indicated. This asymmetry encourages a reinterpretation of the opponent-process explanation of appetitive-aversive interactions. Moreover, the observed effects of the unpaired CS suggest the operation of a salience factor.

Trace conditioning as an inhibitory procedure

Virtually no evidence of excitatory CR acquisition is observed in rabbit eyelid conditioning with a trace-conditioning procedure if the CS-UCS trace interval is greater than a few seconds. The lack of overt CRs following training with a trace-conditioning procedure has traditionally been interpreted as due to the passive decay of the CS stimulus trace over time. However, it is conceivable that a trace interval sufficiently long to preclude CR acquisition may be sufficiently long to teach the subject that the CS signals a UCS-free period, thereby producing an inhibitory CS. To test this proposal, eyelid conditioning in rabbits was conducted in two experiments with a 10-sec trace interval (there being no evidence of excitatory conditioning with this procedure). The trace-CS was then tested for evidence of inhibition with retardation-of-acquisition and summation tests. The trace-CS was shown to have conditional inhibitory properties. These results indicate that the interstimulus interval function in trace conditioning may be determined, in part, by inhibitory associations.