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Selective immunolesioning of the basal forebrain cholinergic system disrupts short-term memory in rats

Leanza, G LU ; Muir, J ; Nilsson, O G LU ; Wiley, R G ; Dunnett, S B and Bjorklund, A LU (1996) In European Journal of Neuroscience 8(7). p.1535-4154
Abstract

Selective depletion of nerve growth factor receptor-bearing neurons in the basal forebrain cholinergic system nuclei by the immunotoxin 192 IgG-saporin offers a new and highly useful tool for the study of the role of the forebrain cholinergic system in cognitive functions. In the present study, we have tested the effects of 192 IpG-saporin in an operant delayed matching-to-position task which has previously been used to discriminate between delay-dependent learning impairments and delay-independent disturbances of non-mnemonic processes. Rats were first trained to criterion performance and then received intraventricular injections of 5 microg of 192 IgG-saporin 4 weeks prior to a second testing session. Rats with 192 IgG-saporin lesions... (More)

Selective depletion of nerve growth factor receptor-bearing neurons in the basal forebrain cholinergic system nuclei by the immunotoxin 192 IgG-saporin offers a new and highly useful tool for the study of the role of the forebrain cholinergic system in cognitive functions. In the present study, we have tested the effects of 192 IpG-saporin in an operant delayed matching-to-position task which has previously been used to discriminate between delay-dependent learning impairments and delay-independent disturbances of non-mnemonic processes. Rats were first trained to criterion performance and then received intraventricular injections of 5 microg of 192 IgG-saporin 4 weeks prior to a second testing session. Rats with 192 IgG-saporin lesions displayed a significant delay-dependent decline in performance compared to normal controls, indicating a deficit in short-term memory. Administration of the muscarinic blocker scopolamine (0.5 mg/kg, i.p.) produced more pronounced impairment in the performance of the normal control rats across all delays, and induced further impairment also in animals with 192 IgG-saporin lesions. These effects were not observed following control injections of methyl scopolamine, suggesting that the impairment induced by scopolamine was due to the blockade of central muscarinic receptors. No improvement in performance was observed in either group following systemic treatment with the muscarinic cholinergic agonist arecoline (1.00 mg/kg). Biochemical and morphological analyses confirmed the selective and severe (>90-95%) depletion of cholinergic neurons throughout the septal-diagonal band area and the nucleus basalis region by the intraventricular 192 IgG-saporin treatment. Although the immunotoxin was observed to produce additional damage to the cerebellar Purkinje cells, no gross motor abnormalities were observed that could contribute to the effects on accuracy in the task used here. In conclusion, the results show that selective combined lesions of the basal forebrain cholinergic neurons in the septal-diagonal band area and nucleus basalis produce long-lasting impairments in short-term memory, thus providing further support for a role of this system in cognitive functions.

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keywords
Animals, Antibodies, Monoclonal/toxicity, Arecoline/pharmacology, Cholinergic Agents/toxicity, Conditioning, Operant/physiology, Female, Hippocampus/physiology, Immunotoxins/toxicity, Memory Disorders/physiopathology, Memory, Short-Term/physiology, N-Glycosyl Hydrolases, N-Methylscopolamine, Parasympatholytics/pharmacology, Prosencephalon/physiology, Rats, Rats, Sprague-Dawley, Reaction Time/drug effects, Ribosome Inactivating Proteins, Type 1, Saporins, Scopolamine/pharmacology, Scopolamine Derivatives/pharmacology, Septum Pellucidum/physiology
in
European Journal of Neuroscience
volume
8
issue
7
pages
1535 - 4154
publisher
Wiley-Blackwell
external identifiers
  • scopus:0029894379
  • pmid:8758961
ISSN
0953-816X
DOI
10.1111/j.1460-9568.1996.tb01616.x
language
English
LU publication?
yes
id
384af287-91d5-45a4-b3e3-109c70d6459a
date added to LUP
2019-06-25 09:52:09
date last changed
2020-02-12 10:09:03
@article{384af287-91d5-45a4-b3e3-109c70d6459a,
  abstract     = {<p>Selective depletion of nerve growth factor receptor-bearing neurons in the basal forebrain cholinergic system nuclei by the immunotoxin 192 IgG-saporin offers a new and highly useful tool for the study of the role of the forebrain cholinergic system in cognitive functions. In the present study, we have tested the effects of 192 IpG-saporin in an operant delayed matching-to-position task which has previously been used to discriminate between delay-dependent learning impairments and delay-independent disturbances of non-mnemonic processes. Rats were first trained to criterion performance and then received intraventricular injections of 5 microg of 192 IgG-saporin 4 weeks prior to a second testing session. Rats with 192 IgG-saporin lesions displayed a significant delay-dependent decline in performance compared to normal controls, indicating a deficit in short-term memory. Administration of the muscarinic blocker scopolamine (0.5 mg/kg, i.p.) produced more pronounced impairment in the performance of the normal control rats across all delays, and induced further impairment also in animals with 192 IgG-saporin lesions. These effects were not observed following control injections of methyl scopolamine, suggesting that the impairment induced by scopolamine was due to the blockade of central muscarinic receptors. No improvement in performance was observed in either group following systemic treatment with the muscarinic cholinergic agonist arecoline (1.00 mg/kg). Biochemical and morphological analyses confirmed the selective and severe (&gt;90-95%) depletion of cholinergic neurons throughout the septal-diagonal band area and the nucleus basalis region by the intraventricular 192 IgG-saporin treatment. Although the immunotoxin was observed to produce additional damage to the cerebellar Purkinje cells, no gross motor abnormalities were observed that could contribute to the effects on accuracy in the task used here. In conclusion, the results show that selective combined lesions of the basal forebrain cholinergic neurons in the septal-diagonal band area and nucleus basalis produce long-lasting impairments in short-term memory, thus providing further support for a role of this system in cognitive functions.</p>},
  author       = {Leanza, G and Muir, J and Nilsson, O G and Wiley, R G and Dunnett, S B and Bjorklund, A},
  issn         = {0953-816X},
  language     = {eng},
  number       = {7},
  pages        = {1535--4154},
  publisher    = {Wiley-Blackwell},
  series       = {European Journal of Neuroscience},
  title        = {Selective immunolesioning of the basal forebrain cholinergic system disrupts short-term memory in rats},
  url          = {http://dx.doi.org/10.1111/j.1460-9568.1996.tb01616.x},
  doi          = {10.1111/j.1460-9568.1996.tb01616.x},
  volume       = {8},
  year         = {1996},
}