Classical conditioning with auditory discrimination of the eye blink in decerebrate cats.

Cats were subjected to complete lower brainstem transection, and were then tested for learning ability according to a classical conditioning paradigm. An auditory stimulus was systematically paired with a brief shock to the eyelid. Within a few weeks after the operation, the decerebrate cats could learn the conditioned response with a tone frequency discrimination and then a discrimination reversal. Our results support the notion that the brainstem reticular formation can support a conditioned response which isbehaviorally similar to that obtained in the intact animal.

Metabolic maturation of the brain: a study of local cerebral glucose utilization in the developing cat.

Previously, using positron emission tomography (PET), we showed that local cerebral metabolic rates for glucose (lCMRglc) in children undergo dynamic maturational trends before reaching adult values. In order to develop an animal model that can be used to explore the biological significance of the different segments of the lCMRglc maturational curve, we measured lCMRglc in kittens at various stages of postnatal development and in adult cats using quantitative [14C]2-deoxyglucose autoradiography. In the kitten, very low lCMRglc levels (0.14 to 0.53 mumol min-1 g-1) were seen during the first 15 days of life, with phylogenetically older brain regions being generally more metabolically mature than newer structures. After 15 days of age, many brain regions (particularly telencephalic structures) underwent sharp increases of lCMRglc to reach, or exceed, adult rates by 60 days. This developmental period (15 to 60 days) corresponds to the time of rapid synaptic proliferation known to occur in the cat. At 90 and 120 days, a slight decline in lCMRglc was observed, but this was followed by a second, larger peak occurring at about 180 days, when sexual maturation occurs in the cat. Only after 180 days did lCMRglc decrease to reach final adult values (0.21 to 2.04 mumol min-1 g-1). In general, there was good correlation between the metabolic maturation of various neuroanatomical regions and the emergence of behaviors mediated by the specific region. At least in the kitten visual cortex, which has been extensively studied with respect to developmental plasticity, the "critical period" corresponded to that portion of the lCMRglc maturational curve surrounding the 60-day metabolic peak. These normal maturational lCMRglc data will serve as baseline values with which to compare anatomical and metabolic plasticity changes induced by age-related lesions in the cat.

Maturation of cerebral oxidative metabolism in the cat: a cytochrome oxidase histochemistry study.

The maturation of brain oxidative capacity was studied in kittens, using cytochrome oxidase histochemistry, at different ages throughout development. Optical densitometry values of reacted tissue were obtained for 50 different structures of the brain. In general, most structures reached adult levels of oxidative capacity by 30 days of age with some motor areas (e.g., cerebellum, red nucleus) exhibiting adult values as early as 7 days of age. Thereafter, some structures (e.g., basal ganglia, thalamus) exhibited levels of cytochrome oxidase activity that exceeded adult values for varying periods of time. These findings indicate regional heterogeneity in the maturation of cerebral oxidative capacity. Furthermore, these maturational patterns appear to correlate well with previous observations from anatomical, physiological and neurobehavioral studies.

Cerebral metabolism following neonatal or adult hemineodecortication in cats: I. Effects on glucose metabolism using [14C]2-deoxy-D-glucose autoradiography.

In the cat, cerebral hemispherectomy sustained neonatally results in a remarkable degree of recovery and/or sparing of function as compared with the effects of a similar lesion but sustained in adulthood. We have proposed that this effect is due to a combination of reduced neuronal loss within partially denervated structures and a lesion-induced reorganization of corticofugal projections arising from the remaining intact hemisphere in the neonatally lesioned animal. The current study was designed to assess the physiological consequences of these anatomical changes utilizing [14C]2-deoxy-D-glucose autoradiography. A total of 17 adult cats were studied. Seven animals served as intact controls, five received a left cerebral hemineodecortication as neonates (NH; mean age 11.4 days), and five sustained the same lesion in adulthood (AH). Histological analysis indicated that the lesion was very similar between the two age groups and essentially represented a unilateral hemineodecortication. Local CMRglc (LCMRglc; mumol 100 g-1 min-1) values were calculated for 50 structures bilaterally and indicated that in the remaining intact contralateral (right) cerebral cortex (including all areas measured), AH cats exhibited a significantly (p < 0.05) lower level of LCMRglc (ranging from 20 to 72 mumol 100 g-1 min-1) than NH (ranging from 49 to 81 mumol 100 g-1 min-1). In comparison, the rates of NH cats within the cerebral cortex were very similar to those seen in intact animals (ranging from 48 to 119 mumol 100 g-1 min-1). Ipsilateral to the lesion in AH cats, the structures spared by the resection, including the basal ganglia and thalamus, exhibited LCMRglc rates of between 23 and 69 mumol 100 g-1 min-1, which were significantly lower (p < 0.05) than in NH cats (range 47-72 mumol 100 g-1 min-1). Considering all structures, both age-at-lesion groups exhibited a lower level of metabolism compared with similar measurements for intact control animals (LCMRglc range 45-75 mumol 100 g-1 min-1). However, this depression of glucose metabolism was more pronounced in the AH cats (p < 0.05). These results indicate that following neonatal hemineodecortication, LCMRglc is maintained at a higher level in many regions of the brain than in animals that sustain the same resection in adulthood. This higher level of glucose metabolism in NH animals suggests that the lesion-induced anatomical reorganization of structures not directly injured by the lesion plays a functional role that is probably responsible for the greater degree of recovery and/or sparing of function in these early lesioned cats.

Developmental neuroplasticity in a model of cerebral hemispherectomy and stroke.

Cerebral hemispherectomy, a last resort treatment for childhood epilepsy, is a standard procedure which dramatically illustrates the resilience of the brain to extensive damage. If this operation, also mimicking long-term, extensive unilateral capsular stroke, is performed in postnatal cats of up to 60 days of age, there is a remarkable recovery/sparing of neurological functions that is not seen when the lesion occurs during late fetal life or in adulthood. A long-term effect at all ages is loss of neurons in bilateral brain areas remote from the resection site. This is pronounced in adult cats and shows intriguing, paradoxical features in fetal animals, but is substantially attenuated in neonatal cats. Similarly, large-scale reinnervation of subcortical sites (sprouting) by neurons of the remaining, intact hemisphere is prominent in young cats, but not in fetal or adult animals. These and other restorative processes (described herein) in young postnatal animals are matched by relatively higher rates of local cerebral glucose utilization, supporting the notion that they underlie the improved behavioral outcome. Thus, during a critical, defined stage of maturation, presumably common to higher mammals including humans, the brain entirely remodels itself in response to extensive but focal injury. Perhaps the molecular environment allowing for rescue of neurons and enhanced reinnervation at a specific developmental stage could be recreated in subjects with brain lesions at less favorable ages, thereby helping to restore circuitry and spare neurons. However, replacement via transplantation of neurons eliminated by the damage appears to be crucial in attempts to further preserve cells located remotely but yet destined to die or decrease in size. This article presents abundant evidence to show that there is a surprisingly comprehensive long-term morphological remodeling of the entire brain after extensive unilateral damage and that this occurs preferentially during a discrete period of early life. Additional evidence strongly suggests that the remodeling underlies the outstanding behavioral and functional recovery/sparing following early cerebral hemispherectomy. We argue that this period of reduced brain vulnerability to injury also exists in other higher mammals, including man, and suggest ways to enhance restorative processes after stroke/hemispherectomy occurring at other ages.

Sleep-waking states develop independently in the isolated forebrain and brain stem following early postnatal midbrain transection in cats.

We report the effects of permanently separating the immature forebrain from the brain stem upon sleeping and waking development. Kittens ranging from postnatal 9 to 27 days of age sustained a mesencephalic transection and were maintained for up to 135 days. Prior to postnatal day 40, the electroencephalogram of the isolated forebrain and behavioral sleep-wakefulness of the decerebrate animal showed the immature patterns of normal young kittens. Thereafter, the isolated forebrain showed alternating sleep-wakefulness electrocortical rhythms similar to the corresponding normal patterns of intact, mature cats. Olfactory stimuli generally changed forebrain sleeping into waking activity, and in cats with the section behind the third nerve nuclei, normal correlates of eye movements-pupillary activity with electrocortical rhythms were present. Behind the transection, decerebrate animals showed wakefulness, and after 20 days of age displayed typical behavioral episodes of rapid eye movements sleep and, during these periods, the pontine recordings showed ponto-geniculo-occipital waves, which are markers for this sleep stage, together with muscle atonia and rapid lateral eye movements. Typically, but with remarkable exceptions suggesting humoral interactions, the sleep-waking patterns of the isolated forebrain were dissociated from those of the decerebrate animal. These results were very similar to our previous findings in midbrain-transected adult cats. However, subtle differences suggested greater functional plasticity in the developing versus the adult isolated forebrain. We conclude that behavioral and electroencephalographic patterns of non-rapid eye movement sleep and of rapid eye movement sleep states mature independently in the forebrain and the brain stem, respectively, after these structures are separated early postnatally. In terms of waking, the findings strengthen our concept that in higher mammals the rostral brain can independently support wakefulness/arousal and, hypothetically, perhaps even awareness. Therefore, these basic sleeping-waking functions are intrinsic properties of the forebrain/brain stem and as such can develop autochthonously. These data help our understanding of some normal/borderline sleep-waking dissociations as well as peculiar states of consciousness in long term patients with brain stem lesions.

The effect of neocortical lesions on the number of cells in neonatal or adult feline caudate nucleus: comparison to fetal lesions.

After a unilateral resection of the frontal cortex in fetal cats the volume of the caudate nucleus increases while the packing density of neuronal and glial cells does not change. In the present report we address the questions of whether a similar lesion sustained neonatally or a more extensive neodecortication sustained neonatally or in adulthood may have the same unusual effect. Stereological methods were used to determine bilaterally the volume of the caudate nucleus as well as to estimate the total number and packing density of neurons and glial cells in the caudate nucleus ipsilateral to the lesion. Comparisons between each of three experimental groups and intact animals were made at a time when all animals were young adults. In cats with a unilateral frontal cortical lesion performed between postnatal days 8 and 14, none of the measured parameters changed significantly compared to intact controls. In cats with removal of the entire left neocortex in adulthood, the ipsilateral caudate nucleus volume decreased by 18.1% and by 21.5% relative to intact and to neonatal hemidecorticated cats respectively (P < 0.05), with no change in the contralateral caudate. In the ipsilateral caudate the total number of neurons decreased by 21.8% (P < 0.05) compared to controls while the number of glial cells did not change significantly. In the same caudate the packing density of neurons did not change significantly (except for a 17.1% decrease, P < 0.05, relative to frontal-lesioned cats) while that of glial cells increased by 19.9% and by 24.7% compared to intact and neonatal neodecorticated cats respectively (P < 0.05). In adult cats in which a similar hemineodecortication was performed between postnatal days 8 and 13, the only significant changes were a 25.8% (P < 0.05) and a 30.6% (P < 0.05) decrease in neuron packing density compared to intact and frontal-lesioned cats, respectively. In summary, a restricted unilateral neocortical resection in neonatal cats did not induce any morphological changes in the caudate nucleus that we could detect with the methods employed. In contrast, an extensive neodecortication sustained in adulthood produced ipsilateral caudate shrinkage with substantial neuron loss and increase in packing density of glial cells, while a similar lesion but sustained neonatally only altered substantially the packing density of glial cells (decreased). Therefore, we concluded that (i) the caudate nucleus hypertrophy which we reported after a unilateral discrete cortical removal during the prenatal period is a unique phenomenon which is peculiar to the cat brain during the last third of gestation; (ii) the caudate nucleus changes seen in the cats with hemineodecortication in adulthood are degenerative in nature and closely resemble those which we reported for other subcortical nuclei following a similar lesion; and (iii) the animals with neonatal hemidecortication are relatively spared from these degenerative effects. Overall, these results indicate that, as for other structures, the morphological changes of the caudate nucleus following neocortical damage depend on the maturational state of the brain at the time of the injury and on the size of the lesion, and support the notion that the consequences of cerebral cortex lesions upon subcortical brain nuclei are of a different nature when sustained in prenatal as compared to postnatal cats.

Sparing of visual field perception in neonatal but not adult cerebral hemispherectomized cats. Relationship with oxidative metabolism of the superior colliculus.

Following cerebral hemispherectomy and using a lick-suppression test, adult-lesioned cats showed a complete contralateral hemianopsia, while neonatal-lesioned animals reliably responded to stimuli presented out to 45 degrees in the visual field contralateral to the lesion. In adult-lesioned cats oxidative metabolism of the superior colliculus ipsilateral to the hemispherectomy was markedly depressed as compared to the contralateral colliculus. In contrast, in the neonatal-lesioned cats this metabolic imbalance was mild. We propose that this ipsilateral depression of oxidative metabolism reflects the loss of excitatory corticotectal input which has been postulated as being partly responsible for the hemianopsia following a unilateral visual cortex ablation. Here we demonstrate, in addition, that this phenomenon is affected by developmental factors and suggest that differential age-at-lesion anatomical effects may also be involved.

Recovery of function after neonatal or adult hemispherectomy in cats. II. Limb bias and development, paw usage, locomotion and rehabilitative effects of exercise.

To investigate the relationship of age-related processes in the recovery of complex motor functions of the limbs, a variety of neurobehavioral assessments were applied to cats with either neonatal (n = 9) or adult (n = 11) removal of the entire left hemitelencephalon (hemispherectomy). Neonatal-lesioned kittens showed no paw preference in reaching for a manipulandum between 5 and 8 weeks of age; thereafter they developed a preference (5.6%) for the unimpaired left limb which persisted throughout adulthood. Adult-lesioned cats showed a significantly greater left bias (13.9%) than neonatal-lesioned cats and they exhibited more abnormal movements and postures when reaching with the impaired limb. Exercising the impaired limb, was effective in reversing the paw preference bias in all lesioned cats. To master a food retrieval task with the impaired limb, adult-lesioned cats required more trials than the neonatal-lesioned group, extensive food deprivation and at least 1 month of postsurgical recovery. However, after mastering this task all cats could continue to perform it indefinitely in their home cages. In a paw print analysis of locomotion, only adult-lesioned cats showed abnormalities including splayed paws, decreased stride length, and adduction of the right hind limb. The results support the 'Kennard Principle' of enhanced recovery following neonatal vs late brain lesions for the present complex motor patterns and are interpreted in the context of neural plasticity and anatomical reorganization during development.

Depth perception in cats after cerebral hemispherectomy: comparisons between neonatal- and adult-lesioned animals.

Depth perception was studied in adult cats following removal of the left cerebral hemisphere as a neonate or as an adult. Both monocular and binocular thresholds were determined using a visual cliff. Although both age-at-lesion groups showed depth perception deficits, the neonatal-lesioned animals performed much worse under binocular conditions on the visual cliff than either adult-lesioned or intact animals. This was primarily due to the lack of a binocular advantage in the neonatal-lesioned cats since their monocular thresholds were similar to that of adult-lesioned animals. Both lesioned groups showed higher monocular thresholds compared to intact animals but this effect reached significance only for the right eye. In addition, the neonatal-lesioned cats showed ocular misalignment which may have contributed to their lack of binocular depth perception. Regardless of these deficits neonatal-lesioned cats were more like intact controls regarding the types of errors made on the visual cliff. Neonatal-lesioned animals and intact controls made random errors, whereas adult-lesioned animals made most of their errors when the shallow shelf was presented on the animals' right side. This may indicate that the adult-lesioned animals have greater motor and/or visual field biases than do neonatal-lesioned cats.

Recovery of function after neonatal or adult hemispherectomy in cats: I. Time course, movement, posture and sensorimotor tests.

Cats with removal of the left hemitelencephalon (hemispherectomy) as neonates (n = 12) or in adulthood (n = 14), were compared using a battery of 16 neurological and behavioral tests given when they were young adults (kittens) or at least 5 months after the lesion (adults). The neonatal-lesioned subjects grew normally and performed markedly and significantly better than adult-lesioned cats in 13 tests covering the wide range of movement, posture and sensory functions which were assessed. None of the animals recovered tactile placing of the right forelimb or a normal vision in the right visual field. However, the overall recovery was outstanding for all cats such that the neonatal-lesioned were hard to differentiate from intact controls in their spontaneous, daily activities. Because the lesions were similar in the two age-at-lesion groups, and since numerous functions were followed for prolonged, comparable postlesion time, we conclude that, after hemispherectomy in the cat, there definitely is greater functional recovery if the lesion is sustained early in life. We propose that the enhanced recovery of function in neonatal-lesioned cats is largely due to the extensive anatomical reorganization which we have demonstrated in ongoing studies, and which contrasts with a lesser remodeling in adult-lesioned cats.

Recovery of functions after neonatal or adult hemispherectomy in cats. III. Complex functions: open field exploration, social interactions, maze and holeboard performances.

Complex behavioral patterns were studied in cats with removal of the entire left cerebral hemisphere either as neonates (n = 10) or adults (n = 11), and in intact control cats (n = 24). Adult-lesioned cats showed decreased open field activity in locomotion, rearing and sniffing. Lesioned kittens showed similar deficits at 100 days of age, but by 150 days of age they resembled normal littermates in all 3 measures. In the presence of another cat, adult-hemispherectomized cats violated species-typical body-buffer space, approaching and attacking other cats. By comparison, normal cats never attacked and seldom approached in the open field. Neonatal-lesioned adults showed only occasional approach and a tendency to sit or stiff-walk in the presence of other cats; attacks were rare. Adult-lesioned cats responded poorly to reversal training for preferred arm of a T-maze, whereas neonatal-lesioned adults were significantly more trainable. Similarly, adult-lesioned cats exhibited a search deficit in a baited holeboard, while neonatal-lesioned adults searched normally. Overall, these results demonstrate that in this animal model, enhanced recovery following early vs adult lesions can also be found in relatively complex, spontaneous behavioral responses not previously studied in this regard.

Neurological and behavioral effects of a unilateral frontal cortical lesions in fetal kittens. I. Brain morphology, movement, posture, and sensorimotor tests.

Nine fetal kittens sustained removal of the left frontal cortex during the last third of gestation (E 43-55) and were compared to animals sustaining a similar lesion postnatally (P 8-14) as well as to littermate controls. Starting after 6 months of age the animals received a comprehensive battery of movement, posture and sensorimotor tests. The prenatal-lesioned cats performed worse in practically all 15 tests applied (significantly in 13 of them) compared to the neonatal-lesioned cats. Impairments included contralateral paresis of the limbs and face, defective limb placing reactions (with almost absence of the contact components) and a slight extensor hypertonus; tactile hypoesthesia in the contralateral face and hind paw; a bias not to use the contralateral forepaw in a food retrieval task, and an ipsilateral body turning bias. The neonatal-lesioned animals only showed minor defects in the contact components of the limb placing reactions and a tendency to a body turning bias. Morphologically, the brains of the prenatal-lesioned cats, but not of neonatal-lesioned or intact control cats, showed bilateral disruption of the cortical sulcal and gyral patterns, shrinkage of the ipsilateral hemisphere, and reduction in volume of the ipsilateral thalamus and cortex. We concluded, contrary to expectations, that the consequences of a prenatal brain lesion in the cat are worse than when a similar lesion is sustained neonatally.

Neurological and behavioral effects of a unilateral frontal cortical lesion in fetal kittens. II. Visual system tests, and proposing an "optimal developmental period" for lesion effects.

Nine fetal kittens sustained removal of the left frontal cortex during the last third of gestation (E 43-55) and were compared to animals sustaining a similar lesion postnatally (P 8-14) as well as to intact littermates. Beginning after 6 months of age, the animals' visual field and depth perception were assessed. In addition, pupil size as well as eye alignment were measured. On two visual field tests the fetal-lesioned cats showed test dependent decrements for some angles of vision. In terms of depth perception, only the prenatal-lesioned animals showed a higher binocular threshold; they also showed ocular misalignment which may have contributed to their depth perception impairment. Moreover, these animals had a larger ipsilateral pupil. The neonatal-lesioned animals were like normal cats for all tests and measurements. We conclude that, as for the tests reported in the preceding paper, the outcome for visual related behaviors of a prenatal frontal cortical lesion in the cat is also worse than that of a similar lesion sustained neonatally. Dysgenetic anatomical changes of the visual system induced indirectly by the frontal lesion are proposed as a possible explanation for these age-at-lesion differences. Based on the present work as well as on the literature, we propose the existence of an "optimal developmental period" for the best behavioral and anatomical outcome of perinatal brain lesions. We argue that this concept fits contemporary data and can better explain the different age-at-lesion effects of brain injury across animals species than the "Kennard Principle" (or "infant-lesion effect").

Novel crossed corticothalamic projections after neonatal cerebral hemispherectomy. A quantitative autoradiography study in cats.

This is a quantitative study of remodeling of the corticothalamic projections in cats with a left cerebral hemispherectomy performed neonatally or in adulthood. Kittens were lesioned at a mean postnatal age of 10 days and compared, as adults, to adult-lesioned cats of prolonged survival time. All cats received injections of [3H]leucine-proline in the right pericruciate cortex and were sacrificed 5 days later. Injection site and terminal field areas were reconstructed from autoradiography-processed tissue. For the 3 animal groups the label filled a similar extent of cortical areas 4 gamma and 3a. Computerized procedures were used to count labeled particles from multiple bilateral sites of ventral thalamic nuclei (VTN), intralaminar nuclei and midline/paramedial regions at 2 thalamic coronal planes. In control cats the only labeling in the hemithalamus contralateral to the injection was in the intralaminar nuclei and medial-most region of VTN but the counts were low. In contrast, the contralateral hemithalamus of neonatal-lesioned cats showed: a significant increase in terminal field density relative to control cats throughout the VTN, at both coronal planes, and with a distribution of labeling different to the intact side (suggesting heterotypic growth); an increase in counts of labeled particles in intralaminar nuclei which was significant for one sampling site; and an increase in counts for midline/paramedial regions which was significant for all sites at the caudal plane. Adult hemispherectomized cats were similar to intacts except for a tendency to increased VTN counts. These novel terminals were interpreted as collateral sprouting of corticofugal fibers from the intact motor cortex which crossed the midline to reinnervate the decorticate hemithalamus. Findings are discussed in the context of our reported behavioral and anatomical results.

Maturation of pyrogen-elicited fever in the kitten.

The febrile response to the endotoxin Salmonella typhosa was studied in developing kittens. We found that kittens younger than 30 days of age generated only a small rise in temperature in response to a standardized endotoxin challenge that consistently causes fever in adult cats. Some degree of febrile response was present at birth, but the dose of pyrogen necessary to elicit a fever was 10-15 times greater than that required in the adult. There was a gradual increase in both the magnitude and duration of fever as a function of age with the largest change occurring after 30 days of age. There was a direct relationship between the ability of the kitten to maintain its body temperature (Tbo) at the room ambient (Ta) and the magnitude of the elicited fever. However, increasing the Ta to thermoneutral (Ta = 30-32 degrees C) did not enhance the thermal response indicating that the failure to elicit the fever is not due to passive effects of Ta. These data suggest that the febrile response to an endotoxin develops over the first 6-7 weeks of the kitten's life and are discussed in relation to other physical variables of development.

There is less thalamic degeneration in neonatal-lesioned than in adult-lesioned cats after cerebral hemispherectomy.

In order to study age-related processes of degeneration and recovery, the left hemitelencephalon was surgically removed in 5 adult cats and 5 neonatal kittens which were compared to 5 intact controls. After long survival, brains were sectioned in the coronal plane and thionine-stained. Drawings of gross and microscopic thalamic structures were made at 4 planes and computer-digitized to provide 7 measures: total thalamic area at planes A 7.5 and A 8.5; counts of neuroglia, small neurons (31-100 microns2) and large neurons (101-1000 microns2); area of neuroglia, small neurons and large neurons. All cellular measurements were in the ventrobasal complex at planes A 8.0 and A 10.0. Morphological changes were found bilaterally in all lesioned cats. Ipsilateral to the ablation in adult-lesioned cats, thalamic area, large neuron count and glia cells size were markedly and significantly decreased (P less than 0.01), while in neonatal-lesioned cats these changes were present but significantly reduced in magnitude compared to adult-lesioned animals. In addition, adult-lesioned cats showed a marked increase in glial cell numbers (P less than 0.01) and a decrease in small neuron size (P less than 0.01), while kitten-lesioned animals did not show changes in these measures. In the intact side of the brain, the thalamus of adult-lesioned cats was decreased in size (P less than 0.01), and glial cells were decreased in number and size (P less than 0.05), while in kitten-lesioned brains there were few changes. In both lesioned groups large neurons showed a significant increase in size (P less than 0.01). We conclude that neonatal hemispherectomy results in markedly less thalamic atrophy, retrograde neuronal degeneration and gliosis than the equivalent lesion in adults. The changes are discussed in the context of the increased neuroanatomical reorganization and functional recovery which were reported in neonatal- vs adult-lesioned animals.

Striatal lesions change the behavioral effects of morphine in cats.

Cats injected with a relatively low single dose of morphine sulfate (0.5-3.0 mg/kg i.p.) exhibit a long-lasting group of behaviors which we quantified via a time-sampling video technique. The dominant events are complex head movements accompanied by discrete paw, ear and body movements with the animal in a quiet posture, all of which appeared to be visually mediated. Cats with extensive lesions of the caudate nuclei do not show this profile; instead they show unspecific locomotor activity proportional to the size of the ablation and to the dose of morphine. These effects are blocked by naloxone in both intact and lesioned animals. The robustness of these results indicate that (i) the striatum is involved in the behavioral effects of morphine, and (ii) that the cat is a useful, sensitive model for the study of the behavioral effects of opiates.

Bilateral pericruciate cortical innervation of the red nucleus in cats with adult or neonatal cerebral hemispherectomy.

We studied remodeling of the remaining corticorubral projections in adult cats sustaining a left cerebral hemispherectomy in adulthood or neonatally using cortical injections of [3H]leucine-proline. Injection sites and terminal fields were reconstructed from autoradiography-processed tissue. In all cats, the label filled similar extents of ares 4 gamma and 3a of the right frontal cortex. We used sections at 8 coronal planes throughout the red nucleus (RN) for computer-assisted analysis of visually estimated density and topography of distribution of terminal label, and for calculation of RN cross-sectional area. Additionally, at 3 coronal planes we further quantified terminal label using computerized procedures (number of particles for surface area). In all lesioned cats we found terminal label in the RN contralateral to the injection site with a topographic distribution similar to that of the RN ipsilateral to the injection in normal or lesioned cats and in absence of any significant shrinkage of the nucleus. The difference between the 2 age-at-lesion groups was that in the cats with neonatal ablation the density of contralateral terminal label was about double that seen in adult-lesioned subjects. However, the amount of contralateral labeling in adult-lesioned cats was substantial and represented a significant increase over the minimal labeling seen in normal cats. There were no differences between groups in labeling or size of the RN ipsilateral to the injection site. For reasons discussed, we interpret the label on the side of the hemispherectomy as representative of reinnervation of the cortically deafferented RN by crossing collaterals of fibers arising in the remaining motor cortex and not as lesion-sustained persistent prenatal connections.

Effects of caudate nuclear or frontal cortical ablation in neonatal kittens or adult cats on the spontaneous firing of forebrain neurons.

In this paper we have determined the long-lasting consequences of caudate and frontal cortical lesions on spontaneous neuronal firing. Lesions were made both in neonatal and adult cats. All recordings were made in adults. Qualitatively, the effects of the caudate ablations were similar whether they had been carried out in kittens or in adult cats. Caudate lesions produced long-lasting (greater than or equal to 1 year) decreases in the spontaneous firing of cortical neurons. These changes were more pronounced when made in neonates than in adults. The distributions of mean interspike intervals were also altered by these caudate lesions in the pallidum and in the ventral lateral nucleus of the thalamus. Again these effects were more marked if the animals were lesioned as neonates than as adults. Frontal cortical lesions inflicted upon adult cats produced more widespread changes in spontaneous firing rates than similar lesions made in neonates. In both groups frontal lesions slowed spontaneous firing and changed the distributions of mean interspike intervals of caudate neurons. These effects were long-lasting (greater than or equal to 1 year in neonatally-ablated animals). Cortical lesions made in adult cats markedly altered thalamic and pallidal spontaneous activity. Similar lesions made in neonates produced relatively small changes in thalamic and pallidal activity.