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PMID: 11880520 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

Selective behavioral and neurochemical effects of cholinergic lesions produced by intrabasalis infusions of 192 IgG-saporin on attentional performance in a five-choice serial reaction time task.

The Journal of neuroscience : the official journal of the Society for Neuroscience ·Vol. 22 ·No. 5 ·2002-03-01 ·Pages 1905-13

McGaughy J, Dalley JW, Morrison CH, Everitt BJ, Robbins TW

Abstract

The effects of the cholinergic immunotoxin 192 IgG-saporin (SAP) (0.0, 0.15, or 0.45 microg/microl; 0.5 microl/hemisphere) infused into the area of the nucleus basalis magnocellularis (NBM) of rats were tested in a five-choice serial reaction time task (5CSRTT) designed to assess visual attention. The effects of this manipulation on acetylcholine efflux in the medial frontal cortex were determined using in vivo microdialysis during the 5CSRTT. Rats with extensive lesions of the NBM (SAP HIGH) showed an array of behavioral deficits in the 5CSRTT hypothesized to represent deficits in central executive function that were associated with severe deficits in accuracy. Lengthening the stimulus duration ameliorated these deficits. Rats with restricted lesions of the NBM (SAP LOW) showed impairments over time on task when tested under standard conditions that were exacerbated by increases in the event rate. The number of choline acetyltransferase-immunoreactive cells in the area of the NBM but not the vertical limb of the diagonal band correlated significantly with accuracy in the task. SAP HIGH rats had significantly lower levels of cortical acetylcholine (ACh) efflux relative to SHAM both before and during the 5CSRTT. SAP LOW rats showed significantly higher levels of cortical ACh efflux before but not during the 5CSRTT. Cortical ACh efflux increased in all rats with the onset of the attentional task. These data provide the first direct evidence for a relationship between selective damage in the basal forebrain with decreased cortical ACh efflux and impaired attentional function.

MeSH Terms
Acetylcholine/metabolism Animals Antibodies, Monoclonal/administration & dosage Attention/drug effects,physiology Basal Nucleus of Meynert/drug effects,physiology Behavior, Animal/drug effects,physiology Cell Count Choice Behavior/drug effects,physiology Choline O-Acetyltransferase/biosynthesis Drug Administration Routes Frontal Lobe/metabolism Immunotoxins/administration & dosage Male Microdialysis N-Glycosyl Hydrolases Neurons/cytology,metabolism Rats Rats, Inbred Strains Reaction Time/drug effects Ribosome Inactivating Proteins, Type 1 Saporins
Chemicals
192 IgG-saporin Antibodies, Monoclonal Immunotoxins Ribosome Inactivating Proteins, Type 1 Choline O-Acetyltransferase N-Glycosyl Hydrolases Saporins Acetylcholine
Authors & Affiliations
5 authors, click to expand affiliations / ORCID
McGaughy J
Department of Experimental Psychology, University of Cambridge, Cambridge CB2 3EB, United Kingdom. [email protected]
Dalley J W
Morrison C H
Everitt B J
Robbins T W
References (41)
41 references, click to expand
  1. The role of basal forebrain neurons in tonic and phasic activation of the cerebral cortex.
    Prog Neurobiol. 1999 Jun;58(3):249-77 PMID: 10341363
  2. Effect sizes and p values: what should be reported and what should be replicated?
    Psychophysiology. 1996 Mar;33(2):175-83 PMID: 8851245
  3. Potentiation of barbiturate-induced alterations in presynaptic noradrenergic function in rat frontal cortex by imidazol(in)e alpha2-adrenoceptor agonists.
    Br J Pharmacol. 1998 Oct;125(3):441-6 PMID: 9806325
  4. Effects of lesions to ascending noradrenergic neurones on performance of a 5-choice serial reaction task in rats; implications for theories of dorsal noradrenergic bundle function based on selective attention and arousal.
    Behav Brain Res. 1983 Sep;9(3):361-80 PMID: 6639741
  5. 192 IgG-saporin: I. Specific lethality for cholinergic neurons in the basal forebrain of the rat.
    J Neuropathol Exp Neurol. 1994 Jan;53(1):95-102 PMID: 8301325
  6. Cholinergic innervation of cortex by the basal forebrain: cytochemistry and cortical connections of the septal area, diagonal band nuclei, nucleus basalis (substantia innominata), and hypothalamus in the rhesus monkey.
    J Comp Neurol. 1983 Feb 20;214(2):170-97 PMID: 6841683
  7. Trans-synaptic stimulation of cortical acetylcholine release after partial 192 IgG-saporin-induced loss of cortical cholinergic afferents.
    J Neurosci. 1996 Oct 15;16(20):6592-600 PMID: 8815935
  8. Locus coeruleus neurons in monkey are selectively activated by attended cues in a vigilance task.
    J Neurosci. 1994 Jul;14(7):4467-80 PMID: 8027789
  9. The effects of selective cholinergic basal forebrain lesions and aging upon expectancy in the rat.
    Neurobiol Learn Mem. 1997 May;67(3):214-27 PMID: 9159760
  10. Increases in cortical acetylcholine release during sustained attention performance in rats.
    Brain Res Cogn Brain Res. 2000 Jun;9(3):313-25 PMID: 10808142
  11. Cholinergic modulation of responses to single tones produces tone-specific receptive field alterations in cat auditory cortex.
    Synapse. 1990;6(2):133-45 PMID: 2237776
  12. Lack of effects of lesions of the dorsal noradrenergic bundle on behavioral vigilance.
    Behav Neurosci. 1997 Jun;111(3):646-52 PMID: 9189279
  13. Basal forebrain lesions in monkeys disrupt attention but not learning and memory.
    J Neurosci. 1994 Jan;14(1):167-86 PMID: 8283232
  14. The cerebral cortex of the rat and visual attentional function: dissociable effects of mediofrontal, cingulate, anterior dorsolateral, and parietal cortex lesions on a five-choice serial reaction time task.
    Cereb Cortex. 1996 May-Jun;6(3):470-81 PMID: 8670672
  15. Cognitive functions of the basal forebrain cholinergic system in monkeys: memory or attention?
    Behav Brain Res. 1996 Feb;75(1-2):13-25 PMID: 8800650
  16. Increased acetylcholine release in the rat medial prefrontal cortex during performance of a visual attentional task.
    Eur J Neurosci. 2000 Aug;12(8):3051-8 PMID: 10971646
  17. Dissociable effects of AMPA-induced lesions of the vertical limb diagonal band of Broca on performance of the 5-choice serial reaction time task and on acquisition of a conditional visual discrimination.
    Behav Brain Res. 1996 Dec;82(1):31-44 PMID: 9021068
  18. Distinct changes in cortical acetylcholine and noradrenaline efflux during contingent and noncontingent performance of a visual attentional task.
    J Neurosci. 2001 Jul 1;21(13):4908-14 PMID: 11425918
  19. Central cholinergic pathways in the rat: an overview based on an alternative nomenclature (Ch1-Ch6).
    Neuroscience. 1983 Dec;10(4):1185-201 PMID: 6320048
  20. Reversal of visual attentional dysfunction following lesions of the cholinergic basal forebrain by physostigmine and nicotine but not by the 5-HT3 receptor antagonist, ondansetron.
    Psychopharmacology (Berl). 1995 Mar;118(1):82-92 PMID: 7597126
  21. Specific effects of idazoxan in a distraction task: evidence that endogenous norepinephrine plays a role in selective attention in rats.
    Behav Neurosci. 1995 Oct;109(5):903-11 PMID: 8554714
  22. AMPA-induced excitotoxic lesions of the basal forebrain: a significant role for the cortical cholinergic system in attentional function.
    J Neurosci. 1994 Apr;14(4):2313-26 PMID: 7512637
  23. Behavioural, histochemical and biochemical consequences of selective immunolesions in discrete regions of the basal forebrain cholinergic system.
    Neuroscience. 1994 Nov;63(1):95-122 PMID: 7898665
  24. Cortical acetylcholine and processing capacity: effects of cortical cholinergic deafferentation on crossmodal divided attention in rats.
    Brain Res Cogn Brain Res. 1997 Oct;6(2):147-58 PMID: 9450608
  25. Sustained visual attention performance-associated prefrontal neuronal activity: evidence for cholinergic modulation.
    J Neurosci. 2000 Jun 15;20(12):4745-57 PMID: 10844044
  26. Selective immunotoxic lesions of basal forebrain cholinergic cells: effects on learning and memory in rats.
    Behav Neurosci. 1995 Aug;109(4):714-22 PMID: 7576215
  27. Deficit in selective and divided attention associated with cholinergic basal forebrain immunotoxic lesion produced by 192-saporin; motoric/sensory deficit associated with Purkinje cell immunotoxic lesion produced by OX7-saporin.
    Neurobiol Learn Mem. 1999 May;71(3):325-52 PMID: 10196110
  28. Basal forebrain cholinergic lesions disrupt increments but not decrements in conditioned stimulus processing.
    J Neurosci. 1995 Nov;15(11):7315-22 PMID: 7472485
  29. Threshold relationship between lesion extent of the cholinergic basal forebrain in the rat and working memory impairment in the radial maze.
    Brain Res. 1999 Nov 20;847(2):284-98 PMID: 10575099
  30. Comparative effects of ibotenic acid- and quisqualic acid-induced lesions of the substantia innominata on attentional function in the rat: further implications for the role of the cholinergic neurons of the nucleus basalis in cognitive processes.
    Behav Brain Res. 1989 Dec 1;35(3):221-40 PMID: 2688683
  31. Behavioural, histological and immunocytochemical consequences following 192 IgG-saporin immunolesions of the basal forebrain cholinergic system.
    Brain Res Bull. 2001 Jan 1;54(1):29-48 PMID: 11226712
  32. Central cholinergic systems and cognition.
    Annu Rev Psychol. 1997;48:649-84 PMID: 9046571
  33. Behavioral vigilance following infusions of 192 IgG-saporin into the basal forebrain: selectivity of the behavioral impairment and relation to cortical AChE-positive fiber density.
    Behav Neurosci. 1996 Apr;110(2):247-65 PMID: 8731052
  34. Locus coeruleus and regulation of behavioral flexibility and attention.
    Prog Brain Res. 2000;126:165-82 PMID: 11105646
  35. Skill development in vigilance: effects of event rate and age.
    Psychol Aging. 1991 Jun;6(2):155-69 PMID: 1863385
  36. Nucleus basalis stimulation facilitates thalamocortical synaptic transmission in the rat auditory cortex.
    Synapse. 1993 Jun;14(2):132-43 PMID: 8392756
  37. Tonic and phasic influence of basal forebrain unit activity on the cortical EEG.
    Behav Brain Res. 2000 Nov;115(2):159-70 PMID: 11000418
  38. Neural correlates of attention and arousal: insights from electrophysiology, functional neuroimaging and psychopharmacology.
    Prog Neurobiol. 1998 Jul;55(4):343-61 PMID: 9654384
  39. Behavioral vigilance in rats: task validation and effects of age, amphetamine, and benzodiazepine receptor ligands.
    Psychopharmacology (Berl). 1995 Feb;117(3):340-57 PMID: 7770610
  40. Bilateral lesions of the subthalamic nucleus induce multiple deficits in an attentional task in rats.
    Eur J Neurosci. 1997 Oct;9(10):2086-99 PMID: 9421169
  41. Effects of ibotenic acid-induced loss of neurons in the medial prefrontal cortex of rats on behavioral vigilance: evidence for executive dysfunction.
    J Psychopharmacol. 1997;11(2):169-78 PMID: 9208380
Article Info
Journal
The Journal of neuroscience : the official journal of the Society for Neuroscience
Abbr.
J Neurosci
ISSN
1529-2401
Email
[email protected]
Published
2002-03-01
Pages
1905-13
Language
English
Region
United States
NLM ID
8102140
PMCID
PMC6758873
Subset
IM
Grants
Wellcome Trust · United Kingdom
External Links
PubMed source PMC Full Text View journal details
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