Medial prefrontal and neostriatal lesions disrupt performance in an operant delayed alternation task in rats

An operant version of the classical delayed alternation task is presented and applied to evaluate the effects of bilateral prefrontal and striatal lesions in rats. Retractable levers in a conventional operant chamber control discrete trial opportunities for making sequential choice responses to the two sides, and the rats are required to maintain repeated nose poke responses to a central panel during the delay interval, which is randomly varied. The operant task provides measures of the speed and accuracy of response alternation and side bias; analysis at different delay intervals provides an index of the memory demands of accurate performance; and analysis of accuracy depending on the response on preceding trials provides measures of proactive interference and perseveration. Following pretraining in the task contingencies, both striatal and prefrontal lesions induced profound deficits in task accuracy, with no change in side bias and only small changes in movement times. The deficit in the prefrontal lesion group recovered more rapidly, neither group showed any change in sensitivity to proactive interference, while the rats with striatal lesions alone exhibited an increased tendency to perseverate incorrect responses on either side. We conclude that the operant delayed alternation task should assist analysis of fronto-striatal function in rats as well as be useful for the analysis of strategies for fronto-striatal repair.

[1]  An attempt to overcome the problem of motor mediation by rats in the delayed non matching‐to‐position task , 1998 .

[2]  H. Uylings,et al.  The role of the medial prefrontal cortex of rats in short-term memory functioning: further support for involvement of cholinergic, rather than dopaminergic mechanisms , 1995, Brain Research.

[3]  M. Pontecorvo,et al.  N-methyl-D-aspartate antagonists and working memory performance: comparison with the effects of scopolamine, propranolol, diazepam, and phenylisopropyladenosine. , 1991, Behavioral neuroscience.

[4]  H. Fibiger,et al.  Locomotor activity, exploration and spatial alternation learning in rats with striatal injections of kainic acid , 1980, Physiology & Behavior.

[5]  V. Johnston,et al.  The nature of the medial wall deficit in the rat. , 1974, Neuropsychologia.

[6]  T. Robbins,et al.  Striatal lesions produce distinctive impairments in reaction time performance in two different operant chambers , 1998, Brain Research Bulletin.

[7]  G. E. Alexander,et al.  Functional architecture of basal ganglia circuits: neural substrates of parallel processing , 1990, Trends in Neurosciences.

[8]  I. Divac Frontal lobe system and spatial reversal in the rat. , 1971, Neuropsychologia.

[9]  G. E. Alexander,et al.  Parallel organization of functionally segregated circuits linking basal ganglia and cortex. , 1986, Annual review of neuroscience.

[10]  J. Muir,et al.  A behavioural analysis of the delayed non-matching to position task: the effects of scopolamine, lesions of the fornix and of the prelimbic region on mediating behaviours by rats , 1997, Psychopharmacology.

[11]  Temporal factors influence recovery of function after embryonic brain tissue transplants in adult rats with frontal cortex lesions. , 1988, Behavioral neuroscience.

[12]  I. Divac,et al.  Retention of spatial delayed alternation in rats with lesions in the frontal lobes. Implications for a comparative neuropsychology of the prefrontal system. , 1973, Brain, behavior and evolution.

[13]  J. D. Brabander,et al.  Comparison of the effects of neonatal and adult medial prefrontal cortex lesions on food hoarding and spatial delayed alternation , 1991, Behavioural Brain Research.

[14]  G. Dawson,et al.  The effects of novel cholinesterase inhibitors and selective muscarinic receptor agonists in tests of reference and working memory , 1993, Behavioural Brain Research.

[15]  J. M. Warren,et al.  THE FRONTAL GRANULAR CORTEX AND BEHAVIOR , 1964 .

[16]  A. Sahgal Behavioural neuroscience : a practical approach , 1993 .

[17]  M. Mishkin,et al.  Comparison of the effects of frontal and caudate lesions on delayed response and alternation in monkeys. , 1960, Journal of comparative and physiological psychology.

[18]  M. Pontecorvo,et al.  Further developments in the measurement of working memory in rodents. , 1996, Brain research. Cognitive brain research.

[19]  I. Divac,et al.  Dissociative effects of selective lesions in the caudate nucleus of cats and rats. , 1975, Acta neurobiologiae experimentalis.

[20]  C. Jacobsen,et al.  Studies of cerebral function in primates. IV. The effects of frontal lobe lesions on the delayed alternation habit in monkeys. , 1937 .

[21]  S. Dunnett,et al.  Bilateral striatal lesions impair retention of an operant test of short-term memory , 1996, Brain Research Bulletin.

[22]  H. Uylings,et al.  Effects of neonatal mediodorsal thalamic lesions on structure and function of the rat prefrontal cortex. , 1994, Brain research. Developmental brain research.

[23]  H. E. Rosvold,et al.  Behavioral effects of selective ablation of the caudate nucleus. , 1967, Journal of comparative and physiological psychology.

[24]  I. Divac Effects of prefrontal and caudate lesions on delayed response in cats. , 1968, Acta biologiae experimentalis.

[25]  T. Steckler,et al.  Effects of procedural parameters on response accuracy: lessons from delayed (non-)matching procedures in animals. , 1996, Brain research. Cognitive brain research.

[26]  A. Björklund,et al.  Graft-induced behavioral recovery in an animal model of Huntington disease. , 1986, Proceedings of the National Academy of Sciences of the United States of America.

[27]  J. Slangen,et al.  Effects of infusion of cholinergic drugs into the prefrontal cortex area on delayed matching to position performance in the rat , 1996, Brain Research.

[28]  S B Dunnett,et al.  Proactive interference effects on short-term memory in rats: I. Basic parameters and drug effects. , 1990, Behavioral neuroscience.

[29]  I. Divac,et al.  “Cognitive” Functions of the Neostriatum , 1979 .

[30]  C. Cotman,et al.  Transplants of purified astrocytes promote behavioral recovery after frontal cortex ablation , 1986, Experimental Neurology.

[31]  Rosvold He,et al.  The effect on delayed-alternation test performance of stimulating or destroying electrically structures within the frontal lobes of the monkey's brain. , 1956 .

[32]  C. Jacobsen,et al.  Studies of cerebral function in primates. I. The functions of the frontal association areas in monkeys. , 1936 .

[33]  N. V. Poll,et al.  Delayed spatial response alternation: Effects of delay-interval duration and lesions of the medial prefrontal cortex on response accuracy of male and female Wistar rats , 1985, Behavioural Brain Research.

[34]  T. Robbins,et al.  Striatal Graft‐Associated Recovery of a Lesion‐Induced Performance Deficit in the Rat Requires Learning to Use The Transplant , 1992, The European journal of neuroscience.

[35]  R. Numan,et al.  Effects of medial septal lesions on operant delayed alternation in rats , 1990, Brain Research.

[36]  S B Dunnett,et al.  Role of prefrontal cortex and striatal output systems in short-term memory deficits associated with ageing, basal forebrain lesions, and cholinergic-rich grafts. , 1990, Canadian journal of psychology.

[37]  Rosvold He The frontal lobe system: cortical-subcortical interrelationships. , 1972 .

[38]  F. Vanhaaren,et al.  Acquisition of conditional associations and operant delayed spatial response alternation: effects of lesions in the medial prefrontal cortex. , 1988 .

[39]  K. Pribram,et al.  Analysis of the effects of frontal lesions in monkey. I. Variations of delayed alternation. , 1955, Journal of comparative and physiological psychology.

[40]  H. E. Rosvold,et al.  Localization of function within the dorsolateral prefrontal cortex of the rhesus monkey. , 1970, Experimental neurology.

[41]  H. Fibiger,et al.  Avoidance, operant and locomotor behavior in rats with neostriatal injections of kainic acid , 1979, Pharmacology Biochemistry and Behavior.

[42]  A. Sahgal,et al.  Effects of nicotine, oxotremorine and 9-amino 1,2,3,4- tetrahydroacridine (tacrine) on matching and non matching to position in rats: no evidence for mnemonic enhancement , 1990, Journal of psychopharmacology.

[43]  S. Dunnett,et al.  Cholinergic blockade in prefrontal cortex and hippocampus disrupts short-term memory in rats. , 1990, NeuroReport.

[44]  J. Aggleton,et al.  Neurotoxic lesions of the perirhinal cortex do not mimic the behavioural effects of fornix transection in the rat , 1996, Behavioural Brain Research.

[45]  I. Divac,et al.  Neostriatal lesions impaired rats' delayed alternation performance in a T-maze but not in a two-key operant chamber. , 1987, Acta neurobiologiae experimentalis.

[46]  N Butters,et al.  Behavioral deficits in monkeys after selective lesions within the middle third of sulcus principalis. , 1971, Journal of comparative and physiological psychology.

[47]  S. Dunnett,et al.  Functional consequences of embryonic neocortex transplanted to rats with prefrontal cortex lesions. , 1987, Behavioral neuroscience.

[48]  A. Hunter,et al.  Photothrombotic lesions of the frontal cortex impair the performance of the delayed non-matching to position task by rats , 1992, Behavioural Brain Research.

[49]  C. B. Ferster,et al.  Schedules of reinforcement , 1957 .

[50]  J. Rawlins,et al.  The septo-hippocampal system and cognitive mapping , 1982, Behavioural Brain Research.

[51]  S. Dunnett,et al.  Unilateral striatal lesions impair response execution on a lateralised choice reaction time task , 1997, Behavioural Brain Research.

[52]  R. Numan Medial septal lesions impair performance on a preoperatively acquired delayed alternation task , 1991, Brain Research Bulletin.

[53]  Dwaine F Emerich,et al.  Rats with partial striatal dopamine depletions exhibit robust and long-lasting behavioral deficits in a simple fixed-ratio bar-pressing task , 1997, Behavioural Brain Research.

[54]  S. Iversen,et al.  Neurotoxic lesions of ventrolateral but not anteromedial neostriatum in rats impair differential reinforcement of low rates (DRL) performance , 1982, Behavioural Brain Research.

[55]  I. Divac,et al.  Behavioral and anatomical consequences of small intrastriatal injections of kainic acid in the rat , 1978, Brain Research.

[56]  M. Mishkin,et al.  Effects of subcortical lesions in monkeys on visual-discrimination and single-alternation performance. , 1958, Journal of comparative and physiological psychology.

[57]  I. Divac,et al.  Selective ablations within the prefrontal cortex of the rat and performance of delayed alternation , 1978 .

[58]  S. Dunnett,et al.  The effects of bilateral striatal lesions on the acquisition of an operant test of short term memory. , 1995, Neuroreport.

[59]  M MISHKIN,et al.  Effects of small frontal lesions on delayed alternation in monkeys. , 1957, Journal of neurophysiology.

[60]  R. Prado-Alcalá,et al.  Cholinergic blockade of the caudate nucleus and spatial alternation performance in rats: overtraining induced protection against behavioral deficits. , 1978, Life sciences.