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(1/1190) Frontal cognitive impairments and saccadic deficits in low-dose MPTP-treated monkeys.

There is considerable overlap between the cognitive deficits observed in humans with frontal lobe damage and those described in patients with Parkinson's disease. Similar frontal impairments have been found in the 1-methyl-4-phenyl-1,2,3, 6-tetrahydropyridine (MPTP) primate model of Parkinsonism. Here we provide quantitative documentation of the cognitive, oculomotor, and skeletomotor dysfunctions of monkeys trained on a frontal task and treated with low-doses (LD) of MPTP. Two rhesus monkeys were trained to perform a spatial delayed-response task with frequent alternations between two behavioral modes (GO and NO-GO). After control recordings, the monkeys were treated with one placebo and successive LD MPTP courses. Monkey C developed motor Parkinsonian signs after a fourth course of medium-dose (MD) MPTP and later was treated with combined dopaminergic therapy (CDoT). There were no gross motor changes after the LD MPTP courses, and the average movement time (MT) did not increase. However, reaction time (RT) increased significantly. Both RT and MT were further increased in the symptomatic state, under CDoT. Self-initiated saccades became hypometric after LD MPTP treatments and their frequency decreased. Visually triggered saccades were affected to a lesser extent by the LD MPTP treatments. All saccadic parameters declined further in the symptomatic state and improved partially during CDoT. The number of GO mode (no-response, location, and early release) errors increased after MPTP treatment. The monkeys made more perseverative errors while switching from the GO to the NO-GO mode. Saccadic eye movement patterns suggest that frontal deficits were involved in most observed errors. CDoT had a differential effect on the behavioral errors. It decreased omission errors but did not improve location errors or perseverative errors. Tyrosine hydroxylase immunohistochemistry showed moderate ( approximately 70-80%) reduction in the number of dopaminergic neurons in the substantia nigra pars compacta after MPTP treatment. These results show that cognitive and motor disorders can be dissociated in the LD MPTP model and that cognitive and oculomotor impairments develop before the onset of skeletal motor symptoms. The behavioral and saccadic deficits probably result from the marked reduction of dopaminergic neurons in the midbrain. We suggest that these behavioral changes result from modified neuronal activity in the frontal cortex.  (+info)

(2/1190) Object location learning and non-spatial working memory of patients with Parkinson's disease may be preserved in "real life" situations.

The presence of a spatial memory deficit in Parkinson's disease (PD) is still a matter of discussion. Nineteen PD patients and 16 controls were given two spatial tests and a non-spatial task. First, the subject was led into a room containing 4 objects and had 10 s to memorize their location. After being led outside, the subject had to place icons representing the objects on a map of the room. Differences between the real and estimated locations were evaluated. Afterwards, the subject had to choose a map showing the correct arrangement of objects from 4 alternatives. Locations of some objects were changed before the second test. The subject had 10 s to detect these changes. One point was given for each change or its absence detected. In the non-spatial working memory task, 8 cards of different shapes were used. The subject had to select a different card each time while the cards were shuffled between choices. Errors consisted of selecting previously chosen cards. The means of the above measures for both groups were compared. Absence of any significant differences suggests that PD patients perform well in "real life" memory tests in contrast to similar computerized tests.  (+info)

(3/1190) A theory of geometric constraints on neural activity for natural three-dimensional movement.

Although the orientation of an arm in space or the static view of an object may be represented by a population of neurons in complex ways, how these variables change with movement often follows simple linear rules, reflecting the underlying geometric constraints in the physical world. A theoretical analysis is presented for how such constraints affect the average firing rates of sensory and motor neurons during natural movements with low degrees of freedom, such as a limb movement and rigid object motion. When applied to nonrigid reaching arm movements, the linear theory accounts for cosine directional tuning with linear speed modulation, predicts a curl-free spatial distribution of preferred directions, and also explains why the instantaneous motion of the hand can be recovered from the neural population activity. For three-dimensional motion of a rigid object, the theory predicts that, to a first approximation, the response of a sensory neuron should have a preferred translational direction and a preferred rotation axis in space, both with cosine tuning functions modulated multiplicatively by speed and angular speed, respectively. Some known tuning properties of motion-sensitive neurons follow as special cases. Acceleration tuning and nonlinear speed modulation are considered in an extension of the linear theory. This general approach provides a principled method to derive mechanism-insensitive neuronal properties by exploiting the inherently low dimensionality of natural movements.  (+info)

(4/1190) Complex behavioral strategy and reversal learning in the water maze without NMDA receptor-dependent long-term potentiation.

Successful performance of the water maze task requires that rats learn complex behavioral strategies for swimming in a pool of water, searching for and interacting with a hidden platform before its spatial location can be learned. To evaluate whether NMDA receptor-dependent long-term potentiation (NMDA-LTP) is required for learning the required behavioral strategies, rats with NMDA-LTP blocked by systemic pharmacological treatment were trained in the behavioral strategies using simplified and stepwise training methods. Despite the blockade of NMDA-LTP in the dentate gyrus and hippocampal area CA1, rats learned the required behavioral strategies and used them to learn both initial and reversed platform locations. This is the first evaluation of the role of NMDA-LTP specifically in behavioral strategy learning. Although hippocampal NMDA-LTP might contribute to the water maze task, this form of LTP is not essential for learning complex behavioral strategies or multiple hidden platform locations.  (+info)

(5/1190) The role of orientation flights on homing performance in honeybees.

Honeybees have long served as a model organism for investigating insect navigation. Bees, like many other nesting animals, primarily use learned visual features of the environment to guide their movement between the nest and foraging sites. Although much is known about the spatial information encoded in memory by experienced bees, the development of large-scale spatial memory in naive bees is not clearly understood. Past studies suggest that learning occurs during orientation flights taken before the start of foraging. We investigated what honeybees learn during their initial experience in a new landscape by examining the homing of bees displaced after a single orientation flight lasting only 5-10 min. Homing ability was assessed using vanishing bearings and homing speed. At release sites with a view of the landmarks immediately surrounding the hive, 'first-flight' bees, tested after their very first orientation flight, had faster homing rates than 'reorienting foragers', which had previous experience in a different site prior to their orientation flight in the test landscape. First-flight bees also had faster homing rates from these sites than did 'resident' bees with full experience of the terrain. At distant sites, resident bees returned to the hive more rapidly than reorienting or first-flight bees; however, in some cases, the reorienting bees were as successful as the resident bees. Vanishing bearings indicated that all three types of bees were oriented homewards when in the vicinity of landmarks near the hive. When bees were released out of sight of these landmarks, hence forcing them to rely on a route memory, the 'first-flight' bees were confused, the 'reorienting' bees chose the homeward direction except at the most distant site and the 'resident' bees were consistently oriented homewards.  (+info)

(6/1190) Path integration absent in scent-tracking fimbria-fornix rats: evidence for hippocampal involvement in "sense of direction" and "sense of distance" using self-movement cues.

Allothetic and idiothetic navigation strategies use very different cue constellations and computational processes. Allothetic navigation requires the use of the relationships between relatively stable external (visual, olfactory, auditory) cues, whereas idiothetic navigation requires the integration of cues generated by self-movement and/or efferent copy of movement commands. The flexibility with which animals can switch between these strategies and the neural structures that support these strategies are not well understood. By capitalizing on the proclivity of foraging rats to carry large food pellets back to a refuge for eating, the present study examined the contribution of the hippocampus to the use of allothetic versus idiothetic navigation strategies. Control rats and fimbria-fornix-ablated rats were trained to follow linear, polygonal, and octagonal scent trails that led to a piece of food. The ability of the rats to return to the refuge with the food via the shortest route using allothetic cues (visual cues and/or the odor trail available) or using ideothetic cues (the odor trail removed and the rats blindfolded or tested in infrared light) was examined. Control rats "closed the polygon" by returning directly home in all cue conditions. Fimbria-fornix rats successfully used allothetic cues (closed the polygon using visual cues or tracked back on the string) but were insensitive to the direction and distance of the refuge and were lost when restricted to idiothetic cues. The results support the hypothesis that the hippocampal formation is necessary for navigation requiring the integration of idiothetic cues.  (+info)

(7/1190) Landmark discrimination learning in the dog.

Allocentric spatial memory was studied in dogs of varying ages and sources using a landmark discrimination task. The primary goal of this study was to develop a protocol to test landmark discrimination learning in the dog. Using a modified version of a landmark test developed for use in monkeys, we successfully trained dogs to make a spatial discrimination on the basis of the position of a visual landmark relative to two identical discriminanda. Task performance decreased, however, as the distance between the landmark and the "discriminandum" was increased. A subgroup of these dogs was also tested on a delayed nonmatching to position spatial memory task (DNMP), which relies on egocentric spatial cues. These findings suggest that dogs can acquire both allocentric and egocentric spatial tasks. These data provide a useful tool for evaluating the ability of canines to use allocentric cues in spatial learning.  (+info)

(8/1190) Head direction cells in rats with hippocampal or overlying neocortical lesions: evidence for impaired angular path integration.

Rodents use two distinct navigation strategies that are based on environmental cues (landmark navigation) or internal cues (path integration). Head direction (HD) cells are neurons that discharge when the animal points its head in a particular direction and are responsive to the same cues that support path integration and landmark navigation. Experiment 1 examined whether HD cells in rats with lesions to the hippocampus plus the overlying neocortex or to just the overlying neocortex could maintain a stable preferred firing direction when the rats locomoted from a familiar to a novel environment, a process thought to require path integration. HD cells from both lesion groups were unable to maintain a similar preferred direction between environments, with cells from hippocampal rats showing larger shifts than cells from rats sustaining only cortical damage. When the rats first explored the novel environment, the preferred directions of the cells drifted for up to 4 min before establishing a consistent firing orientation. The preferred direction was usually maintained during subsequent visits to the novel environment but not across longer time periods (days to weeks). Experiment 2 demonstrated that a novel landmark cue was able to establish control over HD cell preferred directions in rats from both lesion groups, showing that the impairment observed in experiment 1 cannot be attributed to an impairment in establishing cue control. Experiment 3 showed that the preferred direction drifted when HD cells in lesioned animals were recorded in the dark. It was also shown that the anticipatory property of anterodorsal thalamic nucleus HD cells was still present in lesioned animals; thus, this property cannot be attributed to an intact hippocampus. These findings suggest that the hippocampus and the overlying neocortex are involved in path integration mechanisms, which enable an animal to maintain an accurate representation of its directional heading when exploring a novel environment.  (+info)