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P Winn

Publications and source records attributed to P Winn.

At least 19 recordsLinked to original sources
PubMed1998

Excitotoxic lesions of the subthalamic nucleus ameliorate asymmetry induced by striatal dopamine depletion in the rat.

We investigated the effect of unilateral dorsal striatal dopamine depletion (by intrastriatal infusion of 6-OHDA), ibotenic acid lesions of the subthalamic nucleus (STN) and combined dopamine depletion and STN lesions on sensorimotor asymmetry using a test of somatosensory asymmetry [T. Schallert et al., Pharmacol. Biochem. Behav. 16 (1982) 455-462]. The unilateral striatal dopamine depletion resulted in a somatosensory asymmetry. This asymmetry was ameliorated in the rats with combined dopamine depletion and STN lesion. indicating the potential beneficial nature of STN inactivation in rats with striatal dopamine depletion.

Animals↗
PubMed1998

Long-lived picture priming in normal elderly persons and demented patients.

Normal elderly control participants showed short-term (10-min delay) and long-term (12 months delay) priming on the Gollin Figures Test. Nearly all patients with Alzheimer's disease or vascular dementia showed short-term priming, but the magnitude of their priming was less than that of controls. Significant long-term priming was not observed for the dementia groups. Differences between controls and dementia patients on the short-term priming test may depend upon structural-perceptual processes that are intact in dementia patients and controls and explicit memory functions available only to controls. The same model could account for differences between normal elderly and dementia patients on the long-term priming test, but several other explanations are also plausible.

Aged↗
PubMed1997

Neurotoxicity, blood-brain barrier breakdown, demyelination and remyelination associated with NMDA-induced lesions of the rat lateral hypothalamus.

Excitotoxins have been widely used to make lesions in the brains of experimental animals because they have the ability to destroy neurones while sparing fibres of passage. Because loss of fibres of passage can confound the interpretation of lesion effects, this property is of considerable value. Recently, however, there have been reports indicating that excitotoxins acting at different sites within the rat CNS not only destroy neurones but also strip myelin from fibres and compromise the integrity of the blood-brain barrier. However, some reports also indicate that the myelin content of the lesioned area recovers. Excitotoxic lesions of the lateral hypothalamus have been shown to produce local demyelination. The present studies sought to investigate this effect further by (1) defining the time course of demyelination and possible remyelination after excitotoxic lesions of the lateral hypothalamus made with N-methyl-D-aspartate (NMDA); (2) establishing the relationships between neuronal loss, de- and remyelination after various doses of NMDA; and (3) examining the integrity of the blood-brain barrier using an immunohistochemical probe. Our data show that after injection of NMDA into the lateral hypothalamus there was neuronal loss, blood-brain barrier disruption (followed by recovery over approximately 12 days), triggering of reactive gliosis, invasion of the lesioned area by cells from outwith the CNS, demyelination over an area coexistent with but not exceeding the area of neuronal loss, and remyelination. Remyelination occurred over a period of 3 months following the production of the lesion and was associated initially with blood vessels. It occurred across the whole of the lesioned area, not by encroachment from the borders. All doses of NMDA that produced neuronal death also produced demyelination. These data confirm that excitotoxic lesions of the lateral hypothalamus demyelinate fibres, but show for the first time that remyelination occurs here. They are consistent with reports concerning excitotoxin actions at other CNS sites and indicate that de- and remyelination after excitotoxic lesions is a ubiquitous process. Consideration should be given to this when using excitotoxins to make fibre-sparing lesions.

Animals↗
PubMed1997

Expression of game-related and generic knowledge by dementia patients who retain skill at playing dominoes.

Patients with dementia who remain skilled at musical performance or playing bridge fail explicit memory tests for information related to their skills, suggesting that implicit memory mediates their preserved skills. To reexamine this issue, 23 dementia patients and 15 elderly controls of comparable domino-playing skill were compared on tests of naming, verbal fluency, and domino knowledge. On an explicit test of domino knowledge, the patients scored well below the elderly controls, performing no better than students who were unfamiliar with the game. But when game-like situations were created with real dominoes, both the skilled controls and the patients with dementia chose optimal moves and verbally explained their choices equally well. On naming and fluency tests, the skilled patients showed no advantage over patients of comparable dementia severity who had no retained skill. In dementia, some complex knowledge seems intact but is accessible only in particular contexts.

Aged↗
PubMed1997

On the relationships between the striatum and the pedunculopontine tegmental nucleus.

In this essay we consider the role of the pedunculopontine tegmental nucleus as a striatal output station. We review the relevant anatomical, electrophysiological, behavioral, and pathological studies and conclude that the pedunculopontine tegmental nucleus occupies an important position in striatal outflow, receiving motor output from the dorsal striatum and information from the ventral striatum relating to limbic processes of motivation and reinforcement. The hypothesis we present is that the pedunculopontine tegmental nucleus is at the very least an integral component of the limbic-motor interface, although in discussing this concept we also assess the likelihood that the limbic-motor interface is in fact a distributed system-that is, that limbic-motor interfacing is not all done by a single structure in the central nervous system but that different aspects of it are served by different systems. We present the hypothesis that the pedunculopontine tegmental nucleus is one critical site through which limbic information concerned with motivation, reinforcement, and the construction of novel associations can gain access to a stream of motor outflow coming from the caudate-putamen and directed toward pontomedullary systems without reference back to the cerebral cortex. This hypothesis is important because it highlights striatal outflow, which is not processed through the cortical re-entry systems, and also emphasizes the importance of pontine systems in cognitive processing.

Caudate Nucleus↗
PubMed1996

Modulation of dopamine efflux in the nucleus accumbens after cholinergic stimulation of the ventral tegmental area in intact, pedunculopontine tegmental nucleus-lesioned, and laterodorsal tegmental nucleus-lesioned rats.

Microinjections of the cholinergic receptor agonist nicotine and the cholinesterase inhibitor neostigmine were made into the ventral tegmental area (VTA) of urethane-anesthetized rats, and dopamine (DA) efflux in the nucleus accumbens was measured using in vivo chronoamperometry. Dose-dependent increases in the chronoamperometric signals corresponding to increased DA efflux were observed in the nucleus accumbens of normal intact rats after cholinergic stimulation of the VTA. The source of the cholinergic input to the VTA was investigated by making excitotoxic lesions in either the laterodorsal tegmental nucleus (LDTg) or the pedunculopontine tegmental nucleus (PPTg). Compared with sham-operated control animals, which showed the same response as intact, nonlesioned rats, ibotenate lesions of the LDTg attenuated the stimulatory effects of intra-VTA neostigmine on DA efflux in the nucleus accumbens. In contrast, rats with ibotenate lesions of the PPTg showed normal nucleus accumbens DA eflux after intra-VTA injections of neostigmine. Such lesions in the PPTg attenuate DA efflux in the caudate-putamen stimulated by injections of neostigmine into the substantia nigra pars compacta (SNc). The present data show that cholinergic neurons in the LDTg, but not the PPTg, regulate the activity of DA-containing neurons in the VTA, which complements previous data showing that cholinergic neurons in the PPTg regulate DA-containing neurons in the SNc.

Animals↗
PubMed1996

Schedule-induced polydipsia and the nucleus accumbens: electrochemical measurements of dopamine efflux and effects of excitotoxic lesions in the core.

The efflux of dopamine (DA) in the nucleus accumbens (NAcc) core during the acquisition of schedule-induced polydipsia (drinking in response to intermittent food presentation) was measured using rapid scan voltammetry. DA efflux increased throughout the SIP sessions, always reaching a peak after the session had terminated. There was, however, no relationship between the acquisition of the drinking response to intermittent food presentation and DA efflux. When water was absent from the test chamber, DA efflux still increased and reached a peak after food delivery was terminated, dissociating drinking and increased DA efflux. Taken in conjunction with previously presented data, these results suggest that the presence of DA in the NAcc core might be necessary for the development of SIP but that its efflux does not bear a systematic relationship to the acquisition of adjunctive behaviour. In a second experiment the effects of NMDA-induced lesions of the NAcc core on the acquisition and performance of SIP were examined. Lesioned rats did not differ to controls in terms of water intake, mean drinking bout length, latency to panel press for food or to begin drinking. The number of drinking bouts/min was reduced in lesioned rats, but did not reach statistical significance; the number of panel presses/min was significantly reduced in lesioned rats. These data demonstrate that the NAcc core is not necessary for the development of SIP but that elements of performance are affected. This suggests that the development of SIP can be fractionated and that different neural elements control different aspects of its expression. These data are used to support the hypothesis that the NAcc core is involved in focusing behaviour and regulating switching between response options.

Animals↗
PubMed1996

Memory for the changing cost of a reward is mediated by the sublenticular extended amygdala.

The aim of this study was to examine the role of the sublenticular extended amygdala (SEA) in processes of reward and reinforcement. Previous studies have examined the effects of ibotenate lesions in this area on motivation for cocaine reward. In this study, animals were trained to work for sucrose pellets, rather than a drug, on a progressive-ratio schedule of reinforcement. Bilateral intracerebral infusions of ibotenic acid (lesion group) or vehicle (control group) were made into the SEA, following the same procedures as used in previous studies. After recovery from surgery, animals were tested for six sessions on the progressive ratio schedule. The lesion did not result in motivational impairments of the kind that have previously been reported: rather than decreases in breaking point (a measure of motivational strength), the lesion resulted in greater variability of breaking points, with a tendency for lesioned animals to work harder for reward than controls. The SEA-lesioned rats did not show the increase in postreinforcement pause that usually accompanies the increase in perceived work as the number of bar presses for a reward increases. Histological analyses showed that the ibotenate lesions had successfully destroyed the SEA and that damage was also present in adjacent structures. The results are interpreted in terms of a mnemonic, rather than a motivational, deficit.

Amygdala↗
PubMed1996

Is the cuneiform nucleus a critical component of the mesencephalic locomotor region? An examination of the effects of excitotoxic lesions of the cuneiform nucleus on spontaneous and nucleus accumbens induced locomotion.

The cuneiform nucleus and the pedunculopontine tegmental nucleus have both been suggested as possible sites for the mesencephalic locomotor region (MLR), an area from which controlled stepping on a treadmill can be elicited following electrical or chemical stimulation in a decerebrate animal. It has been shown that excitotoxic lesions of the pedunculopontine tegmental nucleus impair neither spontaneous locomotion nor locomotion induced by stimulation of the nucleus accumbens. Excitotoxic lesions of the cuneiform nucleus have not previously been investigated. Rats received either bilateral ibotenate or sham lesions of the cuneiform nucleus combined with bilateral implantation of guide cannulae aimed at the nucleus accumbens. On recovery from surgery spontaneous locomotion was tested, followed by accumbens-stimulated locomotion. For nucleus accumbens stimulation, each rat received bilateral microinjection of each of three doses of d-amphetamine (10.0, 20.0 and 30.0 micrograms) and a vehicle only injection. Locomotor activity was recorded following the injection. In comparison to the sham-lesioned group, the ibotenate-lesioned group showed no differences in either spontaneous or amphetamine-induced locomotor activity. These results suggest that, like the pedunculopontine tegmental nucleus, the cuneiform nucleus is not involved in the direct mediation of spontaneous or accumbens-induced locomotion, and thus is very unlikely to be the anatomical substrate of the MLR. The role of the cuneiform nucleus in other types of behavioural control is discussed.

Amphetamine↗
PubMed1995

Excitotoxic lesions of the pedunculopontine tegmental nucleus disinhibit orofacial behaviours stimulated by microinjections of d-amphetamine into rat ventrolateral caudate-putamen.

Data are presented which support the hypothesis that the pedunculopontine tegmental nucleus serves as an output station for the striatum and, in particular, has a role in the expression of behaviour stimulated from the ventrolateral caudate-putamen, a rodent homologue of the primate putamen. Rats received either bilateral ibotenate or sham lesions in the pedunculopontine tegmental nucleus and bilateral cannulation of the ventrolateral caudate-putamen. Oral motor activities were observed following microinjection of 5.0, 10.0 and 20.0 micrograms d-amphetamine (and vehicle-only control) into the ventrolateral caudate-putamen. As expected, orofacial behaviours such as biting and licking were observed in sham-lesioned rats following this treatment, but pedunculopontine tegmental nucleus-lesioned rats exhibited an increase in the incidence of these oral motor behaviours at all doses of amphetamine compared with the controls. This increase was the product of changes in the duration and number of times in which they engaged in oral motor behaviours, but not the latency to initiate them. There was no change in the normal oral motor activities associated with grooming. Histological analysis showed that ibotenate lesions destroyed both cholinergic and non-cholinergic neurones in the pedunculopontine tegmental nucleus. These data indicate that loss of the pedunculopontine tegmental nucleus disinhibits oral motor behaviours stimulated from the ventrolateral caudate-putamen by d-amphetamine and are discussed in terms of their implications for understanding the relationships between striatal outflow and structures in the pons.

Amphetamine↗
PubMed1995

The pedunculopontine tegmental nucleus: where the striatum meets the reticular formation.

The pedunculopontine tegmental nucleus (PPTg) contains a population of cholinergic neurons (the Ch5 group) and non-cholinergic neurons. There appears to be functional interdigitation between these two groups, which both have extensive projections. The principal ascending connections are with thalamic nuclei and structures associated with the striatum, including the substantial nigra pars compacta. The descending connections are with a variety of nuclei in the pons, medulla and spinal cord, concerned with autonomic and motor functions. In the past, emphasis has been laid on the role of the PPTg in locomotion and behavioural state control. In this review, we emphasise the role of the PPTg in processing outputs from the striatum. The non-cholinergic neurons receive outflow from both dorsal and vental striatum, and lesions of the PPTg disrupt behaviour associated with each of these. Our review indicates that the PPTg is less concerned with the induction of locomotion and more concerned with relating reinforcement (information about which comes from the ventral striatum) with motor output from the dorsal striatum. The conclusions we draw are: (1) the PPTg is an outflow system for the striatum, but also forms a 'subsidiary circuit', returning information to striatal circuitry; in this, the PPTg has an anatomical organisation that resembles that of the substantia nigra. (2) As well as a role in the mediation of REM sleep, cholinergic PPTg neurons have an important role in the waking state, providing feedback into the thalamus and striatum. (3) The precise function of the computations performed on striatal outflow by the PPTg is uncertain. We discuss whether this function is complementary (parallel to other routes of striatal outflow), integrative (modifying other forms of striatal outflow) or both.

Animals↗
PubMed1994

Preserved cognitive skills in dementia of the Alzheimer type.

OBJECTIVE: To describe preserved cognitive skills in patients with dementia. DESIGN: Case series. SETTING: Community clinic. PATIENTS: Five patients who met National Institute of Neurological and Communicative Disorders and Stroke-Alzheimer's Disease and Related Disorders Association criteria for probable Alzheimer's disease and were claimed to retain a cognitive skill. INTERVENTIONS: None. MAIN OUTCOME MEASURES: Standard neuropsychological tests and individualized measures of patient's skilled behaviors. For patients who remained skilled at games, performance was compared with that of normal controls in direct competition. For the patient-trombonist, raters compared premorbid and postmorbid recordings of his play. RESULTS: One patient continued to play the trombone in a Dixieland band, although he could not name well-known numbers that he played. Another continued to solve adult jigsaw puzzles. A third patient retained skill at canasta, the fourth at dominoes. The fifth patient remained a skillful contract bridge player, although he could not name the suits or articulate simple bidding rules. Four patients had impaired performance on standard anterograde and remote memory and naming tests but performed normally on pursuit rotor and letter fluency tests. Mini-Mental State Examination scores for these patients ranged from 10 to 22. One patient refused neuropsychological testing but displayed his skill. CONCLUSIONS: Together with previous studies of preserved piano playing or painting skills, our findings indicate that a broad range of complex cognitive abilities may be preserved in patients with dementia of the Alzheimer type who cannot perform simpler actions.

Aged↗
PubMed1994

The pedunculopontine tegmental nucleus: a role in cognitive processes?

The cholinergic pedunculopontine tegmental nucleus, located in the brainstem and part of the reticular formation, has been traditionally linked to motor function, arousal and sleep. Its anatomical connections, however, raise the possibility that the pedunculopontine tegmental nucleus is also involved in other aspects of behaviour such as motivation, attention and mnemonic processes. This is of obvious importance, since the pedunculopontine tegmental nucleus undergoes degeneration in human neurodegenerative disorders also characterized by attentional and/or mnemonic deficits. Moreover, recent behavioural animal work suggests that cognitive processes may be represented in the pedunculopontine tegmental nucleus. The difficulty that faces research in this area, however is the possible influence of cognition by other processes, such as arousal state, motivation and motor function. Nevertheless, by reviewing the literature, the pedunculopontine tegmental nucleus seems to be involved in attentional and possibly also in learning processes. These processes could be mediated by influencing cortical function via the thalamus, basal forebrain and basal ganglia. The involvement of the pedunculopontine tegmental nucleus in mechanisms of memory, however, seems to be rather unlikely.

Animals↗
PubMed1994

Outflow from the nucleus accumbens to the pedunculopontine tegmental nucleus: a dissociation between locomotor activity and the acquisition of responding for conditioned reinforcement stimulated by d-amphetamine.

Output of neuronal information from the nucleus accumbens to the ventral pallidum is known to be a critical pathway in the expression of locomotion and incentive-related behaviour. Some signals from this structure are relayed forward through the dorsomedial nucleus of the thalamus to the medial prefrontal cortex, but the other major pathway from this site is a descending innervation to the pedunculopontine tegmental nucleus. Information carried by these descending neurons has been linked with both the output of locomotor activity and incentive-related information. Previous studies carried out in this laboratory have shown no changes in locomotor activity--either spontaneous or in response to systemic administration of d-amphetamine or apomorphine--in rats with excitotoxic lesions of the pedunculopontine tegmental nucleus. The present experiments compare the effects of ibotenate lesions of this nucleus in tests of locomotor activity or the acquisition of responding with conditioned reinforcement, following injections of d-amphetamine directly into the nucleus accumbens. In general agreement with previous results, ibotenate lesions of the pedunculopontine tegmental nucleus did not alter locomotion stimulated directly from the nucleus accumbens. However, comparable lesions in a group of trained rats produced an array of deficits in the conditioned reinforcement paradigm. Most notably, these rats directed their attention almost entirely towards pressing the levers (practically ignoring the food-hopper panel), but did not appear to be able to discriminate between them, while controls focused almost all their efforts on pressing the reinforcing lever (virtually ignoring the non-reinforcing lever) and the food-hopper panel. These results indicate that pedunculopontine tegmental nucleus lesions disrupt an element of reward-related responding, but do not affect the production of locomotor activity. This highlights the unlikely existence of specific "locomotion-inducing" centres in the mesencephalon and implicates the pedunculopontine tegmental nucleus in the formation of stimulus-reward associations. These data are discussed with respect to a role for the pedunculopontine tegmental nucleus in response selection.

Animals↗