Relationship between asymmetries in striatal dopamine release and the direction of amphetamine-induced rotation during. The first week following a unilateral 6-OHDA lesion of the substantia nigra

In animals with a large unilateral 6-hydroxydopamine (6-OHDA) lesion of the nigrostriatal dopamine (DA) system the traditional “rotational behavior model” states that amphetamine will induce circling behavior towards the denervated striatum (ipsiversive), that is, away from the side where there is greater amphetamine-stimulated DA release and greater DA receptor stimulation. It is puzzling, therefore, why amphetamine induces contraversive rotation in rats tested 4 days after a unilateral 6-OHDA lesion, despite a 90-95% loss of the dopaminergic input to the striatum by this time. Rats reverse their direction of amphetamine-induced rotation by 8 days post-lesion and turn in the ipsiversive direction thereafter. To try and resolve this paradox, bilateral striatal microdialysis was used to estimate the effects of amphetamine on DA neurotransmission on Day 4 and Day 8 following a large unilateral 6-OHDA lesion of the substantia nigra. On Day 4 post-lesion, amphetamine produced a moderate (around 50% of control) increase in the extracellular concentration of DA in the denervated striatum. This amphetamine-releasable pool of DA was exhausted by a single amphetamine challenge, because a second injection of amphetamine given 3 h after the first did not produce a comparable increase in DA. It is suggested that on Day 4 post-lesion the amount of DA released by amphetamine in the denervated striatum is sufficient to produce greater DA receptor stimulation on that side, because of DA receptor supersensitivity, and this leads to contraversive rotation. On Day 8 post-lesion, amphetamine induced DA release in the intact striatum but had no effect on extracellular DA in the denervated striatum (DA was nondetectable). On Day 8, therefore, DA receptor stimulation would be greatest in the intact striatum, leading to ipsiversive rotation. In conclusion, it is suggested that the seemingly paradoxical reversal in the direction of amphetamine-induced rotation that occurs over the first week following a unilateral 6-OHDA lesion is consistent with the traditional rotational model, and is due to time-dependent changes in the ability of amphetamine to release DA in the denervated striatum. © 1994 Wiley-Liss, Inc.     

Dopamine-rich grafts ameliorate whole body motor asymmetry and sensory neglect but not independent limb use in rats with 6-hydroxydopamine lesions

The capacity of dopamine (DA)-rich embryonic grafts to influence performance in a skilled motor task has been assessed. In two separate experiments, unilateral 6-hydroxydopamine lesions of forebrain DA systems induced a neglect of the contralateral limb and an almost total preference for use of the ipsilateral limb when reaching through the bars of a cage for food pellets. If the food paw was restrained, either by a bracelet or by injection of a local anaesthetic, the lesioned rats would continue to make many reaching attempts with the contralateral paw, but on the great majority of these attempts they were unsuccessful in grasping or retrieving food. DA-rich grafts, reinnervating the denervated caudate-putamen, provided no detectable benefit to the lesioned rats, neither in reducing the ipsilateral bias in their side preference, nor in increasing their success when constrained to reaching with the contralateral limb. This failure to benefit from the grafts is not due to the grafts themselves not being viable, since the same rats showed substantial compensation of whole body motor asymmetries in spontaneous and drug-induced rotation, and a reduction of asymmetry in a battery of neurological tests of sensorimotor function. The results are discussed in terms of the degree of anatomical integration of the grafts into the host neural circuitry, and the neural organization necessary for the performance of different classes of behavior.     

Middle cerebral artery (MCA) stroke produces dysfunction in adjacent motor cortex as detected by intracortical microstimulation in rats

Middle cerebral artery (MCA) stroke in the rat produces impairments in skilled movements. The lesion damages lateral neocortex but spares primary motor cortex (M1), raising the question of the origin of skilled movement deficits. Here, the behavioral deficits of MCA stroke were identified and then M1 was examined neurophysiologically and neuroanatomically. Rats were trained on a food skilled reaching task then the lateral frontal cortex was damaged by unilateral MCA electrocoagulation contralateral to the reaching forelimb. Reach testing and training on two tasks was conducted over 30 post-surgical days. Later, M1 and the corticospinal tract were investigated using intracortical microstimulation (ICMS), anterograde and retrograde axon tracing. A skilled reaching impairment was observed post-surgery, which partly recovered with time and training. ICMS revealed a diminished forelimb movement representation in MCA rats, but a face representation comparable in size to sham rats. Anterograde and retrograde tract tracing suggest that M1 efferents were intact. Although M1 appears to be in the main anatomically spared after MCA stroke its function as assessed electrophysiologically and behaviorally is disrupted.     

Similarities vs. differences in place learning and circadian activity in rats after fimbria-fornix section or ibotenate removal of hippocampal cells

Damage to either the fimbria-fornix or to the hippocampus can produce a deficit in spatial behavior and change in locomotor activity but the extent to which the two kinds of damage are comparable is not known. Here we contrasted the effects of cathodal sections of the fimbria-fornix with ibotenic acid lesions of the cells of the hippocampus (Ammon's horn and the dentate gyrus) on place learning in a swimming pool and on circadian activity. Rats in both ablation groups were impaired relative to control rats in learning a single place response but they did acquire the response as measured by swim latencies, errors, and by enhanced searching on probe trials. They were also more active than the control group on the test of activity. Nevertheless, the fimbria-fornix group was initially more impaired on learning and was more active than the hippocampal group. Analysis of the strategies used in learning indicated that the lesion groups were very similar to each other but different from the control group especially in that at asymptotic performance, rats in both lesion groups made rather tight loops as they swam toward the platform. This strategy likely contributed to the greater proportion of time they spent swimming in the correct quadrant on the subsequent probe trial. These findings confirm that rats with fimbria-fornix or hippocampal damage display impairments in place learning and are hyperactive but also show that there are lesion differences. The results are discussed with respect to the relative effectiveness of the lesions and the possibility that fibers in the fimbria-fornix may mediate some functions that are not attributable to the hippocampus. © 1995 Wiley-Liss, Inc.     

Activation,travel distance,and environmental change influence food carrying in rats with hippocampal,medial thalamic and septal lesions: Implications for studies on hoarding and theories of hippocampal function

Rats transport food from exposed areas to covered areas where they eat it or leave it. Although there is evidence that limbic structures play a role in food transport, their role is controversial. Here it was found that although many rats with large hippocampal, septal/diagonal band of Broca or dorsomedial thalamic lesions did not carry food but ate it where they found it, a few presentations of an auditory stimulus could restore food carrying. Once restored, most features of food carrying in hippocampal rats were normal in relation to food presentation schedules, deprivation levels, ambient illumination, circadian cycles, food size, and eating times. Nevertheless, food carrying impairments reemerged when the testing environment was changed. Hippocampal rats were also excessively responsive to increases in travel distance and stopped carrying food at distances over which control rats would still carry large food pellets. Auditory stimulation did not restore food carrying over long travel distances. The findings that sensory stimulation, environmental change, and travel distance influence food carrying probabilities in rats with limbic system lesions is discussed in relation to research on limbic control of food hoarding and theories of limbic system function.     

Development of tonic immobility in the rabbit: relation to body temperature

Tonic immobility was studied in rabbit pups varying in age from 1 to 30 days. During the 1st 2 postnatal weeks the rabbits were active in an open field, had difficulty walking and executing a righting response, lost body temperature rapidly, and had no, or only short durations of, tonic immobility. After this age they were less active, hopped and righted well, maintained core temperature, and showed increased durations of tonic immobility. Within the 1st 2 postnatal weeks cooling and warming potentiated; thereafter, cooling disrupted and only warming potentiated tonic immobility. The results suggest that rate of heat loss can act as a stimulus to block tonic immobility and increase activity in neonatal rabbits. With development, cooling produces shivering which can disrupt tonic immobility, whereas warming may raise movement initiation thresholds which can potentiate tonic immobility.     

We should de-emphasize the importance of the role we give amines in the LH syndrome

Once amines were implicated in the lateral hypothalamic syndrome, it became accepted that the dominant cause of many of its symptoms was an alteration in amines. We suggest that corticofugal fiber damage may produce some of the behavioral symptoms usually attributed to amine alterations.     

Earlier is not always better: behavioral dysfunction and abnormal cerebral morphogenesis following neonatal cortical lesions in the rat

Rats with lesions of the medial frontal, ventral frontal or posterior parietal cortex in adulthood were compared behaviorally and neuroanatomically in adulthood with rats with similar removals at 7 days of age. The neonatal lesions altered cortical morphogenesis, especially in the ventral frontal and parietal groups, in which there was a marked thinning of remaining cortex distal to the lesion site. Behavior was assessed on an extensive battery of sensorimotor and maze-learning tests. Although there was sparing of function on some tests, the overall result was very little sparing on sensorimotor tests and only partial sparing on tests of maze learning in the frontal groups. The parietal neonates showed sparing on only one sensorimotor task and, in addition, showed unexpected deficits on sensorimotor and maze-learning tasks that were not observed in the adult operates. The results suggest that there may be more localization of function in the infant cortex than is generally believed and that early cortical damage may produce different behavioral effects than similar damage in adulthood.