Biomedical subjects

A Sahgal

Publications and source records attributed to A Sahgal.

At least 19 recordsLinked to original sources

PubMed1995

Psychopharmacological studies in rats responding at touch-sensitive devices.

A multiple choice serial reaction time task was used to investigate visual attention in rats. The intelligence panel consisted of a transparent touch-sensitive device, placed directly in front of a video monitor. Amphetamine (0.2-1.6 mg/kg IP) increased errors of omission and decreased latency to respond, but had no effect on accuracy. The 5-HT agonist quipazine (0.6-2.4 mg/kg IP) increased errors of omission, but did not affect other parameters. ICV administration of hemicholinium-3 (1-4 micrograms) had no effect upon performance. Thus, psychopharmacological manipulations can reliably alter performance in the touch window box, suggesting potential new avenues for rat cognitive testing.

Amphetamine↗

PubMed1995

The role of serotonergic-cholinergic interactions in the mediation of cognitive behaviour.

Cholinergic systems have been linked to cognitive processes such as attention, learning and mnemonic function. However, other neurotransmitter systems, such as the serotonergic one, which may have only minor effects on cognitive function on their own, interact with cholinergic function and their combined effects may have marked behavioural actions. Some studies have dealt with serotonergic-cholinergic interactions, but it is unclear whether both systems affect cognition directly or whether interactions at a behavioural level result from additional alterations in non-cognitive factors. This distinction is difficult, since it is possible that the diverse cholinergic and serotonergic systems serve different roles in the mediation of cognitive processes, both at the neuroanatomical and neurochemical level. Nevertheless, it is possible that cholinergic systems primarily alter accuracy in cognitive tasks, whereas serotonergic neurotransmission modulates behaviour by altering bias (motivation, motor processes). Whether serotonin alters accuracy or bias, however, may also depend on the cognitive process under investigation: it is suggested that attention, stimulus processing and/or arousal can be influenced by both cholinergic and serotonergic systems independently from each other. Cholinergic and serotonergic projections to cortex and thalamus may be of importance in the mediation of these cognitive processes. Serotonergic-cholinergic interactions could also be of importance in the mediation of learning processes and trial-by-trial working memory. The data available do not allow an unambiguous conclusion about the role of these interactive processes in the mediation of long-term reference memory. These processes may rely on serotonergic-cholinergic interactions at the hippocampal level. It is concluded that serotonergic-cholinergic interactions play an important role in the mediation of behavioural, including cognitive, performance, but that further studies are necessary in order to elucidate the exact nature of these interactions.

Acetylcholine↗

PubMed1995

Cholinergic lesions by 192 IgG-saporin and short-term recognition memory: role of the septohippocampal projection.

Two experiments examined the effects of cholinergic basal forebrain lesions by intraventricular and intrahippocampal infusions of the immunotoxin 192 IgG-saporin on recognition memory in an operant delayed-non-matching-to-position task in rats. Intraventricular infusions produced extensive reductions in cortical and hippocampal choline acetyltransferase activity in the first experiment. Behaviourally, a mixed delay-dependent/independent accuracy deficit and increased biased responding was observed post-lesioning. Thus, both mnemonic as well as non-mnemonic processes were affected by the lesion. This performance deficit was indistinguishable from the impairment induced by acute intraventricular injections of the choline uptake inhibitor hemicholinium-3, which suggests that cholinergic damage induced by 192 IgG-saporin disrupted performance. In the second experiment more discrete intrahippocampal 192 IgG-saporin lesions were made, which reduced hippocampal choline acetyltransferase activity about 57%, although this reduction was not as extensive as following intraventricular injections. Although intrahippocampal lesions also impaired non-matching accuracy, this effect failed to reach significance during most stages of the experiment. Scopolamine just failed to significantly impair (P = 0.053) performance in hippocampal lesioned rats more than in controls. The nicotinic antagonist mecamylamine did not affect the lesion-induced changes in performance. These results suggest that the cholinergic basal forebrain, including the septohippocampal system, is important for the mediation of recognition memory, and muscarinic receptor-mediated mechanisms may be of greater importance than alterations of nicotinic receptor-mediated processes in the septohippocampal system.

Acetylcholinesterase↗

PubMed1995

Do differences in visuospatial ability between senile dementias of the Alzheimer and Lewy body types reflect differences solely in mnemonic function?

Visuospatial memory was investigated in two groups of patients suffering from senile dementias of the Alzheimer (SDAT) or Lewy body (SDLT) types; a, third, age-matched, healthy control group was also included. The two patient groups were mildly demented and could not be distinguished from each other by traditional tests of cognitive function. A different pattern of performance emerged in the two groups on a computerised test of spatial working memory, which is a self-ordered pointing task requiring the subject to search for hidden tokens. An analysis of the pattern of errors revealed that the SDLT group made more of both possible types of error ("Within Search" and "Between Search") than the SDAT group. Neither patient groups' performance differed from each other when assessed on a computerised Corsi spatial span task. A measure of planning ability was obtained by examining search strategies. Although an index previously developed to measure the subject's use of a particular strategy in the spatial working memory task failed to detect any differences between the three groups, a novel index was calculated which focuses on performance within a search, and this revealed deficits in both demented groups. Since the two patient groups differed from each other in the spatial working memory, but not the Corsi spatial span, task, it is suggested that the differences between the two demented groups are not due to a specific mnemonic impairment, but reflect dysfunctions in non-mnemonic processes mediated by fronto-subcortical circuits, which are more severely damaged in SDLT.

Aged↗

PubMed1995

A comparison of the effects of medial prefrontal, cingulate cortex, and cingulum bundle lesions on tests of spatial memory: evidence of a double dissociation between frontal and cingulum bundle contributions.

Rats were trained on an automated delayed nonmatching-to-position (DNMP) task. They then received cytotoxic lesions in either the medial prefrontal cortex (n = 13) or the cingulate and retrosplenial cortices (n = 8), or radiofrequency lesions in either the fornix (n = 6) or the cingulum bundle (n = 8). Twelve animals served as surgical controls. Only the fornical and medial prefrontal lesions disrupted DNMP performance, both groups showing a loss of accuracy and an increase in bias. The rats were then trained on a lever discrimination and reversal task, the medial prefrontal and fornical groups showing evidence of an increase in bias when compared with the cingulate cortex group. Finally, the rats were trained on a forced alternation task in a T-maze. Marked deficits were observed in the fornix and cingulum bundle groups, but the medial prefrontal and cingulate groups were unimpaired. The double dissociation between the effects of the prefrontal and cingulum bundle lesions highlights the very different nature of the two spatial tasks (DNMP and T-maze alternation), even though both involved a nonmatching rule. These findings may reflect the involvement of divergent outputs from the fornix-anterior thalamic pathway. One possibility is that anterior thalamic projections to the medial prefrontal cortex are concerned with processing egocentric information, while anterior thalamic projections to temporal regions via the cingulum bundle are concerned with allocentric information. The results also indicate that the effects of conventional lesions in the cingulate cortex and medial prefrontal cortex may be compromised by additional damage to the cingulum bundle.

Animals↗

PubMed1994

Lack of effect of lesions in the anterior cingulate cortex and retrosplenial cortex on certain tests of spatial memory in the rat.

The effects of cytotoxic lesions in either the anterior cingulate cortex or the retrosplenial cortex were compared with those of fornix lesions on three tests of spatial memory. Two of the tasks, delayed nonmatching-to-position and spatial reversal learning, were tested in an automated apparatus. The third task, forced alternation, was tested in a T-maze. Neither anterior cingulate nor retrosplenial cortex damage produced any significant impairment on the three tasks. In contrast, rats with fornix lesions (hippocampal system damage) were markedly impaired on all three tasks. The results, which were considered in the light of proposals for a hippocampal--anterior thalamic--cingulate system that is important for spatial memory, suggest that neither of the cingulate regions involved in this study form a critical subcomponent of this proposed system. It is therefore assumed that the cingulate cortices are only critical for certain classes of spatial problem. It is also suggested that in some previous studies the effects of inadvertent damage to the cingulum bundle may have contributed to the apparent effects of cingulate lesions.

Animals↗

PubMed1994

Lesions of the pedunculopontine tegmental nucleus do not alter delayed non-matching to position accuracy.

The cholinergic pedunculopontine tegmental nucleus, located in the brainstem, and part of the reticular formation, has traditionally been linked to motor function, sleep and arousal, but has recently been implicated in cognition. To investigate this possibility, rats with radiofrequency lesions were tested on a delayed non-matching to position task, a test for spatial recognition memory abilities. Data were analysed according to the methods of signal detection theory. Lesions of the pedunculopontine nucleus did not produce marked deficits in accuracy, although there was some evidence to suggest that motivational processes could have been affected.

Acetylcholine↗

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

TouchWindows and operant behaviour in rats.

We describe a new method which has the potential to assess a wide range of behavioural, especially cognitive, processes in rats. This involves the presentation of microcomputer-generated visual stimuli on a standard video monitor, with the rat responding on a transparent pressure-sensitive device (TouchWindow) placed directly in front of it. The method allows a large variety of visual stimuli to be used, with responses possible over the entire area of the window. In this report, we describe the basic design of the equipment and the training protocol and present behavioural data from a light-tracking (visual attention) task.

Animals↗

PubMed1992

Removal of the hippocampus and transection of the fornix produce comparable deficits on delayed non-matching to position by rats.

Rats with radiofrequency lesions of the fimbria/fornix or with extensive aspiration lesions of the hippocampal region (the hippocampus proper, dentate gyrus, and subicular complex) were tested on their performance of a delayed non-matching to position task which had been learnt before surgery. On a given trial, one of two sample levers was presented in a random manner. Following a response on this lever and a subsequent delay, both levers were presented and reward was now contingent on a response on the lever that was not used as the sample. Both lesions produced equivalent performance deficits on this test of spatial working memory, the pattern of these deficits being consistent with a mnemonic impairment. The lack of difference between these two groups on a variety of performance measures indicates that hippocampal connections passing through the fornix are not only necessary for this test, but that non-fornical hippocampal connections appear unable on their own to maintain accurate responding.

Animals↗

PubMed1992

Matching-to-sample deficits in patients with senile dementias of the Alzheimer and Lewy body types.

Using a computerized matching-to-sample task, nonverbal visual recognition memory was studied in two groups of patients suffering from senile dementia of the Alzheimer type or the recently described senile dementia of the Lewy body type. The patients' cognitive abilities had been shown to be similar according to a number of standard psychometric tests. The two groups did not differ with respect to simultaneous matching-to-sample performance, although both were impaired relative to control. The group with senile dementia of the Lewy body type was severely impaired, relative to the group with senile dementia of the Alzheimer type, when delays (delayed matching to sample) were introduced. The findings suggest that short-term mnemonic processes, mediated by temporal lobe structures, could be more severely affected in senile dementia of the Lewy body type.

Aged↗

PubMed1992

Examination of parameters influencing [3H]MK-801 binding in postmortem human cortex.

[3H]MK-801 binding was used as an index of the glutamate receptor N-methyl-D-aspartate-subtype channel to examine the influence of gender, age, mode of death (agonal status), interval between death and autopsy (postmortem delay), and time in storage at -70 degrees C in well washed homogenate preparations from postmortem human frontal cortex. Basal binding and the modulatory effects of glutamate, glycine, spermidine, and zinc were examined with respect to these variables. Basal binding was sensitive to agonal status, being higher in sudden death cases. The effect of added glutamate and glycine was sensitive to age, with a trend toward lower binding with increasing age. The effect of added spermidine alone was sensitive to storage time at -70 degrees C, the binding being higher with longer storage time. The effect of added zinc was also sensitive to postmortem delay, with zinc causing a greater reduction in binding with shorter postmortem delays. Thus, with the exception of gender, all variables examined influenced [3H]MK-801 binding, highlighting the attention that should be given to these factors in postmortem studies in normal and diseased human subjects.

Aged↗

PubMed1991

Both fornix and anterior thalamic, but not mammillary, lesions disrupt delayed non-matching-to-position memory in rats.

Rats with radiofrequency lesions of the fimbria/fornix, or neurotoxic lesions of the mammillary bodies or the anterior thalamic nuclei were tested on their ability to perform a delayed non-matching-to-position task that had been learnt before surgery. In this task rats had to respond to a sample lever in an operant chamber and, after a variable delay (during which they were required to respond at the magazine tray), press the other lever when both were presented. Extensive mammillary body lesions had no effect on performance. In contrast, lesions in either the anterior thalamic nuclei or the fimbria/fornix produced marked deficits, the pattern of these deficits being consistent with a mnemonic impairment. It is argued that the anterior thalamic nuclei represent an important hippocampal output for spatial problems, but that the mammillary bodies are only necessary for certain types of mnemonic task.

Animals↗

PubMed1991

Cortical serotonin-S2 receptor binding in Lewy body dementia, Alzheimer's and Parkinson's diseases.

The binding of the selective 5-HT2 antagonist [3H]ketanserin has been investigated in the temporal cortex of patients with Alzheimer's disease (SDAT), Parkinson's disease (PD), senile dementia of Lewy body type (SDLT) and neuropathologically normal subjects (control). 5-HT2 binding was reduced in SDAT, PD with dementia and SDLT. SDAT showed a 5-HT2 receptor deficit across most of the cortical layers. A significant decrease in 5-HT2 binding in the deep cortical layers was found in those SDLT cases without hallucinations. SDLT cases with hallucinations only showed a deficit in one upper layer. There was a significant difference in cortical layers III and V between SDLT without hallucinations and SDLT with hallucinations. The results confirm an abnormality of serotonin binding in various forms of dementia and suggest that preservation of 5-HT2 receptor in the temporal cortex may differentiate hallucinating from non-hallucinating cases of SDLT.

Aged↗

PubMed1990

Opposing effects of vasopressin on matching versus non-matching to position: further evidence for response, not memory, modulation.

Rats were trained on either of two related variants of an operant memory task. In the matching to position (MTP) task, one of two retractable response levers appeared, at random, as the sample. A response caused the lever to retract and this was followed by a delay (0-32 s) interval, during which the subjects had to approach and respond at the magazine tray. Both levers were then presented and the rat had to respond, for food reward, to the one which had appeared as the sample. A second group of rats learned non-matching to position (NMTP). This task was very similar to MTP, with one crucial difference: here, the subject had to respond to the lever which had not appeared as the sample. Both groups of rats learned their respective tasks rapidly, performance depending on the delay interval as expected. They were then injected, peripherally, with different doses of arginine-vasopressin (AVP: 0-25 micrograms/kg), a peptide which others have argued improves mnemonic performance. There was evidence to suggest that MTP performance was improved by AVP; on the other hand, NMTP performance appeared to be disrupted. It is suggested that AVP induces a bias towards responding on one side of the two lever test chamber. In other words, it affects motor or motivational, not mnemonic mechanisms.

Animals↗

PubMed1990

Memory following cholinergic (NBM) and noradrenergic (DNAB) lesions made singly or in combination: potentiation of disruption by scopolamine.

Groups of rats were trained on either delayed matching or nonmatching to position tasks, then divided into four subgroups and given the following bilateral lesions: (a) SHAM [vehicle injection into the nucleus basalis magnocellularis (NBM) and dorsal noradrenergic bundle (DNAB)], (b) DNAB (6-hydroxydopamine lesion of the DNAB, vehicle into the NBM), (c) NBM (quisqualic acid lesion of the NBM, vehicle into the DNAB) and (d) DUAL (neurotoxin lesions of both DNAB and NBM). Following postoperative recovery, the DUAL lesion subjects were slightly impaired, but by the seventh day of testing all groups were performing at similar levels. This strongly suggests that quisqualate lesions of the NBM are not sufficient to produce severe and lasting mnemonic disorders resembling those seen in Alzheimer's disease (AD). These data also indicate that the noradrenergic system may not be of critical importance with respect to cognition. It was reasoned that an additional anticholinergic treatment might exacerbate an underlying deficiency. All groups were injected, peripherally, with the cholinergic antagonist scopolamine (0-0.5 mg/kg). This drug dose-dependently disrupted performance in all groups. Moreover, the highest dose had a marked effect in the DUAL group, impairing performance even when no mnemonic burden was present (at zero delay). The results suggest that cholinergic NBM and noradrenergic DNAB lesions produce only transient mnemonic deficiencies. A combination of the two can be disruptive, but longer term task (or reference) memory is the primary process affected, and only under certain conditions. The implication of these findings to research concerning animal models relating to Alzheimer's disease is discussed.

Animals↗

PubMed1989

[D-TRP11]-neurotensin, unlike alpha-flupenthixol, may not block amphetamine-induced hyperactivity in rats.

Recent reports have suggested that neurotensin (NT) and some of its analogues resemble neuroleptics, for example alpha-flupenthixol (FLU), in their ability to suppress locomotor activity. The results obtained support this conclusion, but only if total photocell counts (the "traditional" index) are considered. An improved method of measuring activity--where subjects have to interrupt photocell beams in sequence before a ("conditional") count is registered--suggested, in direct contrast to the total counts index, that the stable analogue of neurotensin [D-Trp11]-neurotensin (DTNT) increased activity slightly (Sahgal and Keith, 1986). The present report is on the effects of DTNT (0-8 microgram/rat, i.c.v.) and FLU (0-1 mg/kg, i.p.) on hyperactivity induced by D-amphetamine (1.5 mg/kg, i.p.). The usual total counts index of activity suggested that FLU and DTNT blocked the increase. On the other hand, conditional count data suggested that only FLU was effective. Both measures indicated that FLU and amphetamine, administered separately, suppressed and enhanced activity, respectively. In contrast, DTNT at these doses had no significant effect on the conditional counts but markedly suppressed total counts. Subsequent observation of DTNT-treated rats placed in small open fields, suggested that the peptide induced marked circling (ambulatory) behaviour, at the cost of other behavioural categories, especially rearing and grooming. It is argued that (a) DTNT may not resemble neuroleptics in its effects on motor behaviour and (b) conditional activity counts, and also measures relating to brief interruptions of photocell beams, can provide useful additional information concerning motor activity.

Amphetamine↗

PubMed1988

Vasopressin and amphetamine, but not desglycinamide vasopressin, impair positively reinforced visual attention performance in rats.

Rats were trained to respond to the lever above which a light stimulus was briefly (0.5 s) presented at unpredictable times. Once the task had been learned to criterion, subjects were injected, intra-peritoneally, with arginine8-vasopressin, desglycinamide arginine8-vasopressin (AVP or DGAVP: 0, 5, 10 or 20 micrograms/kg) or D-amphetamine (AMP: 0, 0.75, 1.5 or 3 mg/kg) prior to test. Attention performance was assessed using several different indices, including percent corrects, sensitivity and responsivity measures derived from signal detection theory, the recently described probability of (response) repetition and switching, and latency to respond. AVP had a disruptive effect on percent corrects at the highest dose and increased response latencies, but DGAVP, which lacks pressor activity, had no behavioral effects. AMP markedly impaired most aspects of performance, and was the only substance to alter response strategies by inducing bias and repetitive responding. It is concluded that (1) contrary to some recent reports, visual attention is disrupted, not improved, by peripherally injected AVP, (2) these effects reflect pressor potency, (3) the disruption induced by AMP reflects response alterations, while the peptide probably affects more cognitive mechanisms, and (4) certain recently described indices are more sensitive than others in detecting response bias.

Animals↗