Rosalind Mary Ridley- MA PhD ScD
- Head of Comparative Cognition Team (retired) at University of Cambridge
Rosalind Mary Ridley
- MA PhD ScD
- Head of Comparative Cognition Team (retired) at University of Cambridge
Retired
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218
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Introduction
Rosalind Mary Ridley did her PhD at the Institute of Psychiatry and then worked in the Division of Psychiatry at the Clinical Research Centre, Northwick Park Hospital from 1977 to 1994 and at the Department of Psychology, University of Cambridge until 2005. She did research in Neuroscience and her current interest is 'Post-Darwinian psychology in the nineteenth century'.
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October 1994 - October 2005
Publications
Publications (218)
In the University of Cambridge psycholgist Rosalind Ridley's 2016 book 'Peter Pan and the Mind of J. M. Barrie: An Exploration of Cognition and Consciousness' (Cambridge Scholars Publishing), we learn that there is more to the story than pirates and children who can fly. Barrie was very aware of the scientific developments of his day, and the origi...
What is Peter Pan all about? Many of us realize that there is a bit more to the stories than a simple fantasy about flying away to a wonderful place in which to play, and that there is something psychologically rather dark about the events in the stories. But J. M. Barrie’s work has not previously been considered from the perspective of either the...
The study of that group of diseases now collectively known as the prion diseases has always been a source of excitement and
argument between scientists. These obscure diseases usually have been of extremely rare occurrence and have had little impact
on the general public. When an epidemic occurs, however, as in the case of bovine spongiform encepha...
Two factors led to the emergence of the “cholinergic hypothesis of geriatric memory dysfunction” (1): evidence that cholinergic blockade in human volunteers leads to impaired acquisition of new information (2,3) and the demonstration of loss of cortical cholinergic activity and loss of cholinergic cell bodies in the basal forebrain
of patients dyin...
Overexpression of human alpha-synuclein (alpha-syn) using recombinant adeno-associated viral (rAAV) vectors provides a novel tool to study neurodegenerative processes seen in Parkinson's disease and other synucleinopathies. We used a pseudotyped rAAV2/5 vector to express human wild-type (wt) alpha-syn, A53T mutated alpha-syn, or the green fluoresce...
Moderate numbers of amyloid plaques with associated argyrophilic dystrophic neurites and cerebral amyloid angiopathy (CAA) but no neurofibrillary tangles (NFTs) were found in the brains of 3 middle-aged common marmosets (Callithrix jacchus) inoculated intracerebrally (i.e.) 6–7 years earlier with brain tissue from a patient with early onset Alzheim...
Cerebral beta-amyloidosis was found in 16/18 marmosets aged <10 yrs and 8/9 marmosets aged >10 yrs, injected intracerebrally with human or marmoset brain homogenate containing beta-amyloid 1-8 years previously. It was found in only 2/12 marmosets aged <10 yrs and 1/15 marmosets aged >10 yrs, injected with synthetic Abeta-peptides, CSF, or brain tis...
Crossed unilateral dopaminergic lesions of the nigrostriatal bundle and unilateral inferotemporal cortex ablations (DA x IT lesions) in marmoset monkeys produced impaired retention of object discriminations first learnt before, or after, the DA lesion but no impairment on new learning of the same type of task. Retention testing of a pre-operatively...
In this paper we undertake a combined analysis of several studies in which marmoset monkeys received immunotoxic lesions of the cortical cholinergic projections from the basal nucleus of Meynert (NBM) bilaterally and/or in combination with immunotoxic lesions of other parts of the cholinergic system or ablations of the target inferotemporal neocort...
Monkeys with crossed unilateral lesions of the dorsomedial thalamus and contralateral ablations of the inferotemporal cortex were mildly impaired on acquisition and retention of visual conditional tasks requiring the integration of information about objects and their positions in space. They were not impaired on other conditional and nonconditional...
The therapeutic potential of glial cell line-derived neurotrophic factor (GDNF) for Parkinson's disease is likely to depend on sustained delivery of the appropriate amount to the target areas. Recombinant adeno-associated viral vectors (rAAVs) expressing GDNF may be a suitable delivery system for this purpose. The aim of this study was to define a...
The therapeutic potential of glial cell line-derived neurotrophic factor (GDNF) for Parkinson's disease is likely to depend on sustained delivery of the appropriate amount to the target areas. Recombinant adeno-associated viral vectors (rAAVs) expressing GDNF may be a suitable delivery system for this purpose. The aim of this study was to define a...
To assess the pattern of infant carrying across time and family members, we counted which animals in 13 well-established family groups of captive-bred marmosets (Callithrix jacchus) carried neonates during the first 8 weeks of life. The neonates were carried almost continuously for the first 3 weeks and then spent progressively more time independen...
Monkeys with unilateral lesions of nigrostriatal dopamine projections were tested on a series of spatial tasks. One task, in which monkeys were required to use one or the other arm to retrieve food rewards from different positions, allowed separate assessment of the use of each arm in each hemi-space in order to distinguish hemi-spatial and hemi-mo...
Monkeys with crossed unilateral excitotoxic lesions of the anterior thalamus and unilateral inferotemporal cortex ablation were severely impaired at learning two tasks which required the integration of information about the appearance of objects and their positions in space. The lesioned monkeys were also impaired at learning a spatial task and a t...
Marmosets (Callithrix jacchus) in a captive breeding colony living in metal caging, with wooden shelves and perches, were assessed by video recording for the time spent on the floor of the cage when that floor was a wire grid above a sawdust-filled tray and when it had been changed to a sawdust-filled tray several days previously. Quantitative anal...
Glial cell line-derived neurotrophic factor (GDNF) has shown potential as a treatment for Parkinson's disease. Recombinant adeno-associated viral vectors expressing the GDNF protein (rAAV-GDNF) have been used in rodent models of Parkinson's disease to promote functional regeneration after 6-OHDA lesions of the nigrostriatal system. The goal of the...
Animal studies investigating the efficacy of neurotrophic factors as treatments for Parkinson's disease (PD) ideally require partial dopamine (DA) lesion models. The intrastriatal 6-hydroxydopamine (6-OHDA) lesion model may be suitable for this purpose. Although this model has been well characterized in rodents, it has not previously been used in m...
We have examined the effects of permanent middle cerebral artery occlusion (pMCAO) in marmoset monkeys over 5 months, using behavioural and magnetic resonance imaging (MRI) techniques. Three marmosets were trained on behavioural tests before pMCAO. Shortly after surgery, these marmosets were scanned with T2-weighted (T2W) and diffusion-weighted (DW...
NXY-059 has substantial protective effects when administered immediately after the onset of ischemia in a primate model of stroke. This study examined the efficacy of this drug when administered 4 hours after onset, a more clinically relevant time point.
Before surgery, marmosets were trained and tested on a number of neurological tests, which asse...
T. H. Huxley was "Darwin's bulldog," and took the offensive in championing the cause of evolution against skeptical scientists and outraged theologians. As such, he took part in one of the great "paradigm shifts" of biology, at the end of the nineteenth century. Huxley was a rigorous scientist and wrote important articles on scientific method, as w...
Three experimental neuroprotective agents (clomethiazole, AR-R15896AR and NXY-059) have recently been tested in a primate model of acute ischaemic stroke. As the experimental techniques used in all three studies were similar and the compounds were administered at clinically relevant doses, a comparative analysis of the functional benefits of these...
Monkeys with unilateral ablations of the inferotemporal (IT) cortex were not impaired on learning or retention of single-pair object discriminations or visuovisual conditional tasks. Addition of an excitotoxic hippocampal lesion to the hemisphere opposite to the IT ablation impaired retention and acquisition of single-pair object discriminations an...
The Stroke Therapy Academic Industry Roundtable noted the need for standardized, well-accepted primate models of stroke to help develop both neuroprotective and restorative therapies. One primate model has been developed using the marmoset, a small New World species of monkey, in which long-term functional deficits can be assessed. The surgery and...
Transient contralesional spatial neglect, in addition to motor impairment in the contralesional arm, is sometimes seen in patients following cerebral infarction in the right hemisphere and is seen following experimental occlusion of the right middle cerebral artery in primates. To test whether contralesional visuospatial neglect arises from a disru...
Clinical studies in humans and experiments in macaques suggest that damage to the anterior and the mediodorsal thalamus can induce a moderate amnesia, but a more dense impairment may result from substantial damage within the temporal lobes or their subcortical connections. Lesions of the anterior thalamus in macaques produce impairments which resem...
It has been proposed that isolation of the inferior temporal cortex and medial temporal lobe from their cholinergic afferents results in a severe anterograde amnesia. To test this hypothesis directly, seven rhesus monkeys received a unilateral immunotoxic lesion of the cholinergic cells of the basal forebrain with an ipsilesional section of the for...
Monkeys with excitotoxic lesions of the CA1/subiculum region in the right hemisphere and with immunotoxic lesions of the cholinergic cells of the diagonal band in the left hemisphere were impaired on a visual conditional task. In this task, correct choice of one of two objects depends on which of two background fields both objects are presented aga...
Inferotemporal ablations in the New World monkey, the common marmoset (Callithrix jacchus), produced a persistent impairment on visual discrimination learning and a florid, but transient, Klüver-Bucy syndrome. Monkeys with these ablations were impaired on acquisition of object discriminations to a high criterion and on concurrent discrimination lea...
Marmoset monkeys with excitotoxic lesions confined to cornu ammonis subfields 1-3, subiculum and pre-subiculum, but sparing the entorhinal cortex, were impaired on retention and learning of conditional object-choice discriminations. For each of these discriminations, the monkeys were required to choose one of two objects depending on which of two p...
In vitro studies have consistently demonstrated a link between cholinergic neurotransmission and amyloid precursor protein metabolism, although few studies have examined such a relationship in vivo and none have been conducted in primate species. The purpose of this study was to test the hypothesis that a reduction in cholinergic activity in neocor...
Marmoset monkeys (Callithrix jacchus) with bilateral transections of the anterior temporal stem, amygdala and fornix were unable to relearn a 2-choice object discrimination first learnt prior to surgery, and were very severely impaired at relearning a concurrent object discrimination task which they had learnt and relearnt prior to surgery, indicat...
NXY-059 is a novel nitrone with free radical-trapping properties that has a considerable neuroprotective effect in rats. We have now examined the efficacy of this drug at reducing long-term functional disability in a primate model of stroke.
Twelve monkeys were trained and tested on a variety of behavioral tasks used to dissociate and quantify moto...
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There is little published evidence for protection of white matter with neuroprotective drugs in animal models of stroke, yet white matter protection may be important in achieving clinical efficacy. We have examined the effects of NXY-059, a nitrone-based free radical trapping agent, on long-term functional disability in a primate model of stroke...
"Science is nothing but trained and organized common sense, differing from the latter only as a veteran may differ from a raw recruit."(a) Prion disease is a disease of the second half of the twentieth century, but the scientific method that has elucidated this fascinating group of diseases is much older. As an illustration of this, this chapter co...
The hippocampus is a suitable brain area for reconstruction using transplanted cells. The hippocampus is clinically important because it is implicated in memory functions and is particularly vulnerable to ischaemic damage associated with myocardial infarction, head injury, and birth trauma. Its cholinergic afferent system is vulnerable in neurodege...
The low affinity, use-dependent, N-methyl-D-aspartate (NMDA) antagonist, AR-R15896AR, is neuroprotective against transient focal cerebral ischemia in rats. We have examined the effect of AR-R15896AR, administered at a plasma level that is tolerated in acute stroke patients, on both functional and histopathologic measures in marmoset monkeys with pe...
Permanent occlusion of the M1 segment of the middle cerebral artery (pMCAO) in the marmoset, a New World species of monkey, produces unilateral functional deficits, including motor neglect with the contralesional arm and contralesional spatial hemineglect. In this study we examined whether clomethiazole, a drug which modulates the gamma-aminobutyri...
Central glutamate neurotransmission is modulated by an upregulatory cholinergic influence and an inhibitory serotonergic influence. In Alzheimer's disease, cognitive decline is associated with loss of both glutamatergic and cholinergic neurones (Francis et al., 1992, Progress in Neurobiology 39, 517-545). While therapeutic strategies for alleviatin...
Cerebral beta-amyloid occurs in elderly animals of some species and in Alzheimer's disease. Previously, we injected 3 young marmosets intracerebrally with brain tissue from a patient with Alzheimer's disease. Six years later, when the monkeys were middle aged, we found moderate numbers of intracerebral plaques and cerebrovascular deposits containin...
Monkeys, with unilateral immunotoxic lesions of the basal nucleus of Meynert that remove cholinergic innervation of the ipsilesional neocortex, and ablations of the contralateral inferotemporal neocortex, were impaired on retention of visual discriminations learnt before surgery and on acquisition of new discriminations. This demonstrates that the...
Common marmosets (Callithrix jacchus, n = 18) were trained to discriminate between rewarded and non-rewarded objects (simple discriminations, SDs) and to make conditional discriminations (CDs) when presented sequentially with two different pairs of identical objects signifying reward either in the right or left food well of the Wisconsin General Te...
Monkeys with immunotoxic lesions of both the basal nucleus of Meynert and the vertical limb of the diagonal band of Broca (NBM+VDB) lost cholinergic innervation throughout the cortex and hippocampus. They were impaired at learning discriminations between objects differing in either few, or many, attributes and at learning visuospatial conditional d...
The epidemic of bovine spongiform encephalopathy (BSE) has been the most expensive disaster ever to have befallen farming in the UK. It is believed to have led to a new form of spongiform encephalopathy in humans and as yet there is no way of knowing how many people will die of this disease. In order to curtail the BSE epidemic major decisions had...
It is widely believed that common marmosets (Callithrx jacchus) typically give birth to twins under natural conditions. In captivity, however, births of triplets or even larger litters are common, although parents rarely succeed in rearing more than two offspring. The traditional interpretation is that captive conditions, notably the ready availabi...
Immunotoxic lesions of the diagonal band of Broca (VDB) in monkeys disrupted cholinergic input to the hippocampus, producing impaired learning of visuospatial conditional discriminations but not simple visual discriminations. Immunotoxic lesions of the basal nucleus of Meynert (NBM) deprived the cortex of most of its cholinergic input, producing im...
Clomethiazole (CMZ) (Zendra) is neuroprotective in rodents following focal and global ischemia. However, its neuroprotective effects in other species, particularly on functional outcome, have not been reported. We have therefore examined the ability of CMZ to ameliorate the functional deficits produced by a focal cerebral ischemic lesion in the mar...
The effect of excitotoxic lesions of the hippocampus on acquisition and reversal of simple and conditional tasks was investigated using a Y-maze. Hippocampal-lesioned rats were severely impaired on acquisition and reversal of a conditional visuo-spatial task (where different pairs of visually distinctive choice arms indicated whether a left or righ...
Prion protein (PrP) immunohistochemical staining of the brains of common marmosets (Callithrix jacchus) with experimental transmissible spongiform encephalopathy is described. The monkeys (n = 17) had been injected, intracerebrally, 17-49 months previously with homogenates of brain tissue taken post mortem from a cow with BSE (n = 2 monkeys), a she...
This study investigated the effects of dizocilpine (MK‐801) on learning ability in a non‐human primate. Acquisition and reversal learning of visual discrimination tasks and acquisition of visuo‐spatial discrimination tasks were assessed in marmosets using the Wisconsin General Test Apparatus. Dizocilpine impaired acquisition of visuo‐spatial (condi...
The way in which breeding families of laboratory-born marmosets used the space provided by their cages, and a small protruding 'veranda', was assessed in order to determine the popularity of the veranda as a form of environmental enrichment, and the extent to which the marmosets confined themselves to only part of the cage. The veranda was found to...
Huntington's disease is an autosomal dominant, inherited disorder that results in progressive degeneration of the basal ganglia (especially the neostriatal caudate nucleus and putamen) and other forebrain structures and is associated with a clinical profile of movement, cognitive and psychiatric impairments for which there is at present no effectiv...
In humans, administration of the cholinergic antagonist scopolamine impairs the encoding of information into long-term memory and has effects on other cognitive processes. It has been supposed that it is inhibition of the rising cholinergic projections from the basal forebrain, specifically from the basal nucleus of Meynert (NBM) to the neocortex a...
The study examined the importance of embryonic donor age for the survival of nigral grafts in 6-OHDA-lesioned marmosets. The issue as to whether donor age is critical for the survival of nigral grafts in primates is controversial, because several early reports suggested that relatively old tissue could survive transplantation and produce functional...
Four groups of monkeys (Callithrix jacchus) were injected with saline or increasing amounts of the immunotoxin, ME20.4 IgG-saporin, directly into the basal nucleus of Meynert via a frontal trajectory which avoided damage to the overlying basal ganglia. ME20.4 IgG binds to the primate p75 low-affinity neurotrophin receptor; when the saporin deriviti...
The effect of the non-competitive N-methyl-D-aspartate (NMDA)-receptor antagonist, dizocilpine (MK-801) on the acquisition and reversal of conditional tasks was investigated using a Y-maze. Dizocilpine-treated rats were severely impaired on acquisition of a visuo-spatial task and were unable to learn the reversal of this task. 'Worse than chance' p...
The study examined the importance of embryonic donor age for the survival of nigral grafts in 6-OHDA–lesioned marmosets. The issue as to whether donor age is critical for the survival of nigral grafts in primates is controversial, because several early reports suggested that relatively old tissue could survive transplantation and produce functional...
Replicating biological information is usually stored only within nucleic acid. The existence of 'strains' of agent in prion disease (scrapie, BSE, CJD) has been taken to indicate an independent genome within the transmissible agent. Other replicable information exists, however, both in biology and elsewhere, including, for example, the 'meme' (the...
Monkeys with bilateral excitotoxic lesion of the CA1 field of the hippocampus were severely impaired at learning visuospatial conditional tasks. This was not a general spatial impairment, because the animals were not impaired on serial spatial reversal, which requires response flexibility in the spatial domain; they were not impaired at learning to...
Monkeys with dysfunction of the septo-hippocampal system induced by excitotoxic lesion of the CA1 region of the hippocampus, or the septal/diagonal band area (which sends cholinergic projections to the hippocampus via the fornix), or with fornix transection were impaired on conditional learning tasks (when X choose A not B, when Y choose B not A) w...
The distribution of neurones that could be stained immunohistochemically with antibody to the p75 neurotrophin protein was studied in the forebrain of the common marmoset. The p75-immunoreactive forebrain cells appear to correspond to choline acetyltransferase-immunoreactive (i.e., cholinergic) neurones. Two populations of cells could be distinguis...
Information about the outside world is carried into the hippocampus by glutamatergic pyramidal cell pathways from the posterior association cortex via the subiculum. Processed information is carried away from the hippocampus by a reciprocal glutamatergic pathway back into posterior association cortex. These pathways are thought to be crucial for th...
Fornix transection in the marmoset produces a specific pattern of cognitive deficits, notably a lack of ability to recall visuospatial tasks learnt preoperatively, and a deficit in acquiring new visuospatial tasks following transection. Previous work has shown that this learning impairment can be ameliorated by cholinergic agonists, suggesting that...
The apparent existence of multiple strains of the 'transmissible agent' associated with spongiform encephalopathy (prion disease) has been used to support the argument that these diseases are caused by an independent, replicating agent with its own genome. However, the length of the incubation period (time from injection of infected material to ons...
The purpose of the present study was to examine and quantify the functional consequence of a focal cerebral ischaemic lesion in a primate species, the marmoset. Following craniotomy and retraction of the frontal and temporal lobes, the middle cerebral artery was permanently occluded by means of electrocoagulation. Three and eight weeks after surger...
Fornix transection in the marmoset produces a specific pattern of cognitive deficits, notably a lack of ability to recall visuospatial tasks learnt preoperatively, and a deficit in acquiring new visuospatial tasks following transection. Previous work has shown that this learning impairment can be ameliorated by cholinergic agonists, suggesting that...
It seems unlikely that anyone could have foretold the interest, controversy, and concern that the occurrence of bovine spongiform encephalopathy (BSE) in cattle in Great Britain would cause when the author was commissioned to investigate its epidemiology in the spring of 1987. The epidemic has proved to be the largest food-borne epidemic of a trans...
EDITOR,—R W Lacey admonishes us for failing “to provide any of the evidence supporting the occurrence of vertical and horizontal transmission of the infectious agent for bovine spongiform encephalopathy under farm conditions.”1 The data from commercial farms regarding the occurrence of bovine spongiform encephalopathy in the offspring of cows that...
The recent report of 10 cases of a new variant of Creutzfeldt-Jakob disease (CJD) which could be related to bovine spongiform encephalopathy (BSE) has precipitated alarm throughout Europe. The beef trade in the UK has collapsed and the European beef market has been seriously damaged. What went wrong? Much of the difficulty of handling the BSE epide...
Data from a large series of experiments on marmosets with lesions of the septal/diagonal band area (DB), fornix or CA1 area of the hippocampus are analysed in terms of retention of information learned before surgery, acquisition of new information and retention of information acquired after surgery. It is shown that although all three lesions impai...
EDITOR,—We are pleased that, in the commentary on our article on the myth of maternal transmission of spongiform encephalopathy, R G Will agrees that maternal transmission does not occur in human or experimental forms of spongiform encephalopathy and that the only circumstance in which it requires serious consideration is natural scrapie.1
The gen...
Traditionally, confirmation of Transmissible Sponglform Encephalopathy (TSE) disease in humans or animals is by conventional light microscopy of stained tissue sections prepared from specific sites of formalin-fixed tissue after embedding in paraffin wax. This is the statutory method of confirmation of Bovine Spongiform Encephalphathy (BSE) in the...
The pathogenesis of scrapie and other transmissible spongiform encephalopathies (TSEs) appears to be based on the posttranslational conversion of the host’s protease-sensitive prion protein (PrP-sen or PrPc) to abnormal protease-resistant forms (PrP-res or PrPSc). In vitro studies using both scrapie-infected tissue culture cells and cell-free react...
