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Biomedical subjects

D G Lavond

Publications and source records attributed to D G Lavond.

36 records · Page 2Linked to original sources
PubMed1987

Reacquisition of classical conditioning after removal of cerebellar cortex.

We trained rabbits with white noise and light conditioned stimuli and a face shock unconditioned stimulus for classical conditioning of the nictitating membrane response and then removed the ipsilateral cerebellar cortex by aspiration. Larsell's hemisphere lobule VI was completely removed in 5 rabbits; the pattern of degeneration in the inferior olive matches the projections to HVI reported in experiments with horseradish peroxidase. All rabbits showed an initial abolition of conditioned responses but then relearned within two days. This indicates that cerebellar cortical lobule HVI normally is involved but is not necessary for classical conditioning.

Animals↗
PubMed1987

Classical conditioning of the rabbit eyelid response with a mossy-fiber stimulation CS: II. Lateral reticular nucleus stimulation.

Stimulation of mossy fibers arising from the pontine nuclei can be used as a conditioned stimulus (CS) during classical conditioning of the eyelid/nictitating membrane response (NM). In the present experiment we stimulated another source of mossy fibers, the lateral reticular nucleus (LRN), as a CS for NM conditioning. LRN stimulation was an effective CS, resulting in learning, and the conditioned response to LRN stimulation showed normal extinction. Unpaired presentation of CS and UCS did not result in pseudo-conditioning. Lesions of the cerebellar dentate-interpositus region abolished the conditioned response but left the unconditioned reflex response intact. We suggest that mossy fibers may normally carry CS information to the cerebellum.

Afferent Pathways↗
PubMed1987

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.

Acoustic Stimulation↗
PubMed1986

Rapid transfer of training occurs when direct mossy fiber stimulation is used as a conditioned stimulus for classical eyelid conditioning.

Fifteen rabbits were classically conditioned using stimulation of the right pontine nuclei as a conditioned stimulus and a corneal airpuff as an unconditioned stimulus. After conditioning criterion was reached, the stimulation conditioned stimulus was transferred to the left pontine nuclei and the rate of conditioned response acquisition observed. Our results indicate that when electrodes were placed symmetrically in the right and left pontine nuclei, extremely rapid transfer of training occurred. Together with previous data, the present data supply further indirect evidence that the site of neural plasticity which underlies acquisition and retention of classically conditioned skeletal muscle responses is located efferent to the pontine nuclei, namely in the cerebellum.

Animals↗
PubMed1986

Classical conditioning of the rabbit eyelid response with a mossy-fiber stimulation CS: I. Pontine nuclei and middle cerebellar peduncle stimulation.

The nictitating membrane/eyelid responses of 18 rabbits were classically conditioned using cerebellar mossy-fiber stimulation as a conditioned stimulus (CS) and air puff as an unconditioned stimulus (US). The dorsolateral, lateral, and medial pontine nuclei and the middle cerebellar peduncle were effective stimulation-CS sites for training. In one group of rabbits, robust conditioned eyelid responses were produced with paired trials and subsequently extinguished with CS-alone and explicitly unpaired presentation of the CS and US. In a second group of rabbits, no conditioned responses were evident for 4 days of unpaired CS and US presentations. Conditioned responses did develop, however, after paired training was begun. Lesions of the interpositus nucleus of the cerebellum completely abolished the conditioned responses of a third group of rabbits overtrained with the mossy-fiber CS and air-puff US. These results support previous studies which have demonstrated that the cerebellum is critically involved in acquisition and retention of simple learned responses. In addition, the present results support previous theories of cerebellar function which have proposed that mossy fibers supply critical "learning" input to the cerebellum for acquisition and retention of motor skills.

Animals↗
PubMed1985

Trace conditioning: abolished by cerebellar nuclear lesions but not lateral cerebellar cortex aspirations.

The trace conditioning paradigm in which the conditioned stimulus-unconditioned stimulus (CS-US) interval is longer and the US and CS do not overlap requires retention of a 'trace' of the CS to associate it with the US. This task is difficult, requiring for learning about 5 times the number of trials to criterion as the standard delay task. The present study was undertaken to determine if: the cerebellar interpositus nucleus is essential in trace as well as in delay conditioning; and the lateral cerebellar cortex is involved when CS-US association over longer time intervals is required. Sixteen adult male New Zealand white rabbits had recording and in some cases lesion electrodes surgically implanted before training. They were trained daily with 126 paired trials of tone CS and airpuff US. The trace period between CS offset and US onset was 500 ms. Mean number of trials to criterion of 8/9 CRs was 466.9 trials. After a day of overtraining the animals had one of 3 surgeries: electrolytic lesion of the left cerebellar interpositus nucleus (n = 3); aspiration of the left lateral cerebellar cortex (HVI and HVIIA) and underlying cerebellar nuclei (n = 4); or aspiration of HVI and HVIIA only (n = 9). Rabbits with only HVI and HVIIA removed exhibited a transient decrease in CRs but relearned with significant savings. The amplitude, area and latency of pre- and postlesion conditioned responses (CRs) was similar. When the interpositus nucleus was damaged, the animals' capacity for CRs on the side ipsilateral to the lesion was permanently abolished. It is concluded that the cerebellar interpositus nucleus but not the overlying lateral cerebellar cortex is essential for retention of trace classical conditioning. Nevertheless, the temporary abolition of CRs by removal of lateral cerebellar cortex suggests that the cerebellar cortex does play an important role in learning and retention of the trace conditioned response.

Animals↗
PubMed1985

Effect of kainic acid lesions of the cerebellar interpositus nucleus on eyelid conditioning in the rabbit.

It has been shown previously that unilateral electrolytic lesions of the cerebellar dentate-interpositus nuclei selectively abolish or prevent a classically conditioned nictitating membrane/eyelid response in rabbits but do not prevent retention or learning on the contralateral side. The present study demonstrates that kainic acid lesions of the dorsal interpositus nucleus are sufficient for this effect.

Animals↗
PubMed1985

Cerebellar lesions abolish an avoidance response in rabbit.

Unilateral lesions of the cerebellar dentate-interpositus (DI) nuclei abolished or impaired the reacquisition of a nictitating membrane (NM) conditioned avoidance response (CAR) in rabbits. Animals that sustained damage to the DI nuclei and surrounding areas displayed little or no reacquisition of the NM-CAR ipsilateral to the lesion, but displayed excellent acquisition of the response when training was shifted to the contralateral eye. These results agree with previous investigations of the effects of cerebellar lesions on the classically conditioned NM and leg-flexion responses. The DI nuclei appear to be essential for the retention of conditioned responses in a variety of associative paradigms.

Acoustic Stimulation↗
PubMed1984

Effect of bilateral lesions of the dentate and interpositus cerebellar nuclei on conditioning of heart-rate and nictitating membrane/eyelid responses in the rabbit.

It has been shown that unilateral lesions of the medial dentate/lateral interpositus nuclear region of the cerebellum abolish the learned nictitating membrane (NM)/eyelid response of the eye ipsilateral to the lesion. The present study examined the effects of bilateral cerebellar lesions on acquisition of heart-rate conditioning (often viewed as a measure of 'conditioned fear') and both its short-and long-term effects on NM/eyelid learning and relearning. The results demonstrate that cerebellar lesions that completely and permanently abolish acquisition or retention of the somatic response (NM/eyelid) bilaterally have no effect on heart-rate conditioning. The neuronal circuits necessary for learning of the heart-rate response and for learning of the adaptive somatic response are thus in significant part different. Results are tentatively interpreted within the context of a two-process theory of aversive learning: an initial phase indexed by conditioned autonomic and 'non-specific' responses such as heart-rate and a subsequent phase of learning the specific adaptive responses.

Animals↗
PubMed1984

Effects of lesions of cerebellar nuclei on conditioned behavioral and hippocampal neuronal responses.

Rabbits were overtrained using classical conditioning of the rabbit nictitating membrane (NM)/eyelid response. Unilateral electrolytic lesions were then made through electrodes previously implanted in dentate and interpositus cerebellar nuclei ipsilateral to the trained (left) eye. Lesions caused a complete or near-complete abolition of conditioned behavioral responses on the ipsilateral side, but had no effect on unconditioned responses to corneal airpuff. When training was switched to the contralateral (right) side, animals learned within the first few trials, but did not relearn when training was returned to the left (lesioned) side. Control animals in which lesions spared the deep nuclei showed no such learning deficits. Lesions of cerebellar nuclei also abolished conditioned increases in hippocampal CAl neural activity evoked by the tone conditioned stimulus in this paradigm. As with the behavior, training on the right (non-lesioned) side reinstated the conditioned neuronal response within the first few trials of training, even though behavioral responding on lesioned side showed little or no improvement. These results indicate that the cerebellum is an essential structure for the behavioral expression of learning, and plays an important role in the generation of conditioned hippocampal responses observed in this paradigm.

Animals↗
PubMed1983

Neuronal responses of the rabbit brainstem during performance of the classically conditioned nictitating membrane (NM)/eyelid response.

Through the use of a chronic microdrive recording system, neuronal unit activity was recorded throughout the brainstem of the rabbit during performance of the classically conditioned nictitating membrane (NM) extension/eyeblink response using an acoustical conditioned stimulus (CS) and a corneal airpuff unconditioned stimulus (UCS). Regions which exhibited neuronal responses near the onset of the learned response were found to be relatively localized to: the abducens, accessory abducens, and facial nuclei (the motoneurons known to innervate the muscles responsible for expression of the conditioned response); the sensory nuclei of the fifth (probably representing somatosensory or proprioceptive feedback from the conditioned response); the superior colliculus; the periaqueductal gray; various reticular regions and the brainstem nuclei directly connected with the cerebellum (pontine nuclei, tegmental reticular nucleus (Bechterew), red nucleus, and perhaps the inferior olive). Stimulus (tone-airpuff) evoked responses were found within all classical auditory nuclei of the brainstem; the superior colliculus; the periaqueductal gray; pontine nuclei; fifth sensory nuclei, and various reticular regions. Recent lesion studies have shown the ipsilateral cerebellum to be essential for the learning and retention of this response. Collectively these results indicate that the cerebellum and its related brainstem nuclei are critically involved in the control and production of the classically conditioned NM/eyeblink response and may contain essential long term neuronal changes--the 'memory trace'--which serves to encode this learned response.

Acoustic Stimulation↗
PubMed1983

Abolition of conditioned heart-rate responses in rabbits following central administration of [N-MePhe3, D-Pro4] morphiceptin.

Rabbits were initially habituated to a tone and then give 15-20 paired trials where the tone was followed by periorbital shock resulting in conditioned heart-rate decelerations to tone onset and an acceleration of heart-rate following shock offset. The animals were matched for learning performance and divided into two groups. Each animal received a microinfusion into the region of the fourth ventricle of either the opiate [N-MePhe3,D-Pro4] morphiceptin, a highly selective mu receptor agonist, or a mixture of the morphiceptin analogue and the opiate antagonist naltrexone. Administration of the morphiceptin analogue eliminated the conditioned bradycardia to the tone but not the acceleration to the shock. Rabbits given the mixture continued to show conditioned heart-rate decelerations. Previous studies have shown that opiates abolish a recently learned conditioned nictitating membrane response. These effects are consistent with the hypothesis that the opiate effect on conditioning is due to an attenuation of conditioned fear.

Acoustic Stimulation↗
PubMed1982

Concomitant classical conditioning of the rabbit nictitating membrane and eyelid responses: correlations and implications.

Simultaneous recordings of muscle unit activity from the muscles of the left and right eyelids (M. obicularis oculi) and recordings of the movement of the left nictitating membrane (NM) were taken during classical conditioning in the rabbit using a tone CS paired with an airpuff UCS to the left cornea. The unconditioned eyelid responses were found to be bilateral. The conditioned eyelid responses were also bilateral in most animals. Both the conditioned and unconditioned eyelid responses were larger on the left side. The conditioned responses of the left and right eyelids and the left NM were found to increase in magnitude and decrease in latency from the onset of the CS over training trials in almost the exactly same manner (correlations as high as .99). Behaviorally, the three responses could occur independently, suggesting that the cranial nuclei which control them (left abducens/accessory abducens, left facial nucleus, right facial nucleus) are not strongly coupled. Thus, for the learned response, it is suggested that the three nuclei are controlled by a common central system. This finding has implications for the nature of the engram--the essential neuronal circuitry encoding the learned response.

Abducens Nerve↗
PubMed1982

Initial localization of the memory trace for a basic form of learning.

Electrophysiological recording of neuronal unit activity during paired training trials from various regions of the ipsilateral cerebellum in rabbits well trained in the classically conditioned eyelid/nictitating membrane response have revealed both stimulus-evoked responses and responses that form an amplitude/temporal model of the learned behavioral response. Ablation of the ipsilateral, lateral cerebellum completely and permanently abolished the behavioral conditioned response in well-trained animals but had no effect at all on the unconditioned reflex response. In marked contrast, conditioned responses were easily trained in the eye contralateral to the cerebellar lesion. We suggest that at least part of the essential neuronal plasticity that codes the learned response may be localized to the cerebellum.

Animals↗
PubMedDate not supplied

Classical conditioning in 3-, 30-, and 45-month-old rabbits: behavioral learning and hippocampal unit activity.

Evidence has accumulated to suggest that the hippocampus is impaired by aging processes. Hippocampal multiple unit activity was examined in 3-, 30-, and 45-month-old rabbits during classical conditioning in the trace paradigm. Animals were trained daily with 126 paired trials of tone and airpuff. The 3-month-olds learned to a criterion of 8/9 CR's in a mean of 3.2 days, while the 30-month-olds took a mean of 9.4 days, and the 45-month-olds took a mean of 11.75 days. Neural unit activity in the hippocampus modeled the behavioral eyelid response but took much longer to develop in the older animals. Results suggest that rabbits as young as 2 1/2 years old show behavioral and correlated neural response deficits.

Aging↗
PubMedDate not supplied

The effects of reversible inactivation of the red nucleus on learning-related and auditory-evoked unit activity in the pontine nuclei of classically conditioned rabbits.

The pontine nuclei carry auditory conditioned stimulus information to the cerebellum during classical conditioning of the nictitating membrane response in rabbits. In well-trained animals learning-related as well as stimulus-evoked unit activity can be recorded throughout the pontine nuclei but particularly in the lateral and dorsolateral pons. Recent work in our laboratory has provided evidence that the learning-related unit activity in the pons is dependent on the interpositus nucleus and that the pons is not a site of essential plasticity for the learned response. In the present study we considered the question of whether learning-related unit activity might be projected from the interpositus nucleus to the pons through the red nucleus, a primary output target of the interpositus and a structure known to be essential for expression of the learned response. Multiple unit recordings were taken from lateral and dorsolateral pontine locations in well-trained rabbits before and during cooling of the red nucleus. Analysis of pooled data for all recording locations within the lateral and dorsolateral pons indicated that reversible inactivation of red nucleus abolished both stimulus-evoked and learning-related unit activity. However, we also found discrete recording locations where stimulus-evoked and learning-related unit activity were attenuated but not abolished by red nucleus cooling.

Animals↗
PubMedDate not supplied

The learning-related activity that develops in the pontine nuclei during classical eye-blink conditioning is dependent on the interpositus nucleus.

A growing body of research now implicates the cerebellum in the formation and storage of the critical neural plasticity that subserves the classically conditioned eye-blink response. Previous anatomical, physiological, and behavioral research suggests that auditory-conditioned stimulus information is routed to the cerebellum by the pontine nuclei. However, it has also been observed from multiple unit recordings that some populations of pontine cells, in addition to showing auditory-evoked responses, also show changes in activity that is learning-related. It is unknown whether this learning-related activity is generated by the pontine cells or whether it is generated by some other structure and projected to the pontine nuclei. Because the cerebellum has been implicated in the formation of the essential plasticity that subserves this learned behavior, we examined how multiple unit recordings of learning-related activity within the pontine nuclei are affected by reversible inactivation of the interpositus nucleus of the cerebellum. The results indicated clearly that when the interpositus nucleus was inactivated, the learning-related activity in the pontine nuclei was abolished completely and the auditory stimulus-evoked activity was unaffected. In contract, when the facial nucleus was inactivated, both the auditory stimulus and the learning-related activity were still present. These results indicate that the learning-related activity exhibited by some populations of pontine nuclei cells is dependent on the interpositus nucleus and may represent feedback from the cerebellum.

Animals↗