Memory and postsynaptic cholinergic receptors in aging mice

Kubanis, Patricia; Zornetzer, Steven F.; Freund, Gerhard

doi:10.1016/0091-3057(82)90086-7

Cited by 48 publications

(9 citation statements)

References 21 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Enrichment also rectifies genetically induced cognitive deficits, such as those associated with hippocampal deletion of NMDA receptor 1 (Rampon et al, 2000). Even innate cognitive decline associated with aging is forestalled by exposure to enriched housing (Kubanis et al, 1982;Soffie et al, 1999;Frick and Fernandez, 2003). Our findings demonstrate that the benefits of environmental enrichment also extend to a mouse model for Alzheimer's disease, in which exposure to environmental stimulation can abate the behavioral consequences of APPswe and/or A␤ overproduction.…”

Section: Discussionmentioning

confidence: 53%

Environmental Enrichment Mitigates Cognitive Deficits in a Mouse Model of Alzheimer's Disease

Jankowsky¹,

Melnikova²,

Fadale³

et al. 2005

J. Neurosci.

454

293

View full text Add to dashboard Cite

Epidemiological studies suggest that individuals with greater education or more cognitively demanding occupations have diminished risk of developing dementia. We wanted to test whether this effect could be recapitulated in rodents using environmental enrichment, a paradigm well documented to attenuate behavioral deficits induced by various pathological insults. Here, we demonstrate that learning and memory deficits observed in a transgenic mouse model of Alzheimer's disease can be ameliorated by enrichment. Female transgenic mice overexpressing amyloid precursor protein and/or presenilin-1 and nontransgenic controls were placed into enriched or standard cages at 2 months of age and tested for cognitive behavior after 6 months of differential housing. Enrichment significantly improved performance of all genotypes in the radial water maze and in the classic and repeated-reversal versions of the Morris water maze. However, enrichment did not benefit all genotypes equally. Mice overproducing amyloid-␤ (A␤), particularly those with amyloid deposits, showed weaker memory for the platform location in the classic Morris water maze and learned new platform positions in the repeated-reversals task less quickly than their nontransgenic cagemates. Nonetheless, enrichment normalized the performance of A␤-overproducing mice to the level of standard-housed nontransgenic mice. Moreover, this functional preservation occurred despite increased neuritic plaque burden in the hippocampus of double-transgenic animals and elevated steady-state A␤ levels, because both endogenous and transgene-derived A␤ are increased in enriched animals. These results demonstrate that the generation of A␤ in vivo and its impact on the function of the nervous system can be strongly modulated by environmental factors.

show abstract

Section: Discussionmentioning

confidence: 53%

Environmental Enrichment Mitigates Cognitive Deficits in a Mouse Model of Alzheimer's Disease

Jankowsky¹,

Melnikova²,

Fadale³

et al. 2005

J. Neurosci.

454

293

View full text Add to dashboard Cite

show abstract

“…Such an arrangement would permit greater learning specificity, flexibility, and increased convergence and interaction with other pathways and neurotransmitters. Such a postsynaptic mechanism of learning may be more generally applicable to higher organisms, including mammals, where central rather than peripheral correlates to learning have long been known (31,32) and where AcCho has been indirectly implicated in learning (2,4,(33)(34)(35).…”

Section: Discussionmentioning

confidence: 99%

Cholinergic suppression: a postsynaptic mechanism of long-term associative learning.

Morielli¹,

Matera²,

Kovac³

et al. 1986

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

Food avoidance learning in the mollusc Pleurobranchaea entails reduction in the responsiveness of key brain interneurons in the feeding neural circuitry, the paracerebral feeding command interneurons (PCNs), to the neurotransmitter acetylcholine (AcCho). Food stimuli applied to the oral veil of an untrained animal depolarize the PCNs and induce the feeding motor program (FMP). Atropine (a muscarinic cholinergic antagonist) reversibly blocks the foodinduced depolarization of the PCNs, implicating AcCho as the neurotransmitter mediating food detection. AcCho applied directly to PCN somata depolarizes them, indicating that the PCN soma membrane contains AcCho receptors and induces the FMP in the isolated central nervous system preparation. The AcCho response of the PCNs is mediated by muscariniclike receptors, since comparable depolarization is induced by muscarinic agonists (acetyl-fi-methylcholine, oxotremorine, pilocarpine), but not nicotine, and blocked by muscarinic antagonists (atropine, trifluoperazine). The nicotinic antagonist hexamethonium, however, blocked the AcCho response in four of six cases. When specimens are trained to suppress feeding behavior using a conventional food-avoidance learning paradigm (conditionally paired food and shock), AcCho applied to PCNs in the same concentration as in untrained animals causes little or no depolarization and does not initiate the FMP. Increasing the concentration of AcCho 10-100 times, however, induces weak PCN depolarization in trained specimens, indicating that learning diminishes but does not fully abolish AcCho responsiveness of the PCNs. This study proposes a cellular mechanism of long-term associative learningnamely, postsynaptic modulation of neurotransmitter responsiveness in central neurons that could apply also to mammalian species.The neurotransmitter acetylcholine (AcCho) has long been implicated indirectly in the mediation oflearning and memory in invertebrates and vertebrates alike, including humans. In invertebrates, for example, drugs that affect AcCho-mediated transmission alter visual learning in Drosophila (1). In vertebrates, intravenous administration of muscarinic antagonists, such as scopolamine and atropine, interferes with acquisition of conventional avoidance learning tasks in rats (2, 3). In humans, normal and pathological age-related deficits in learning and memory are associated with deficits in AcCho metabolism (4).Although cholinergic systems have thus been implicated indirectly in learning, their role has not been established or analyzed directly. Here we utilize a molluscan "model" system to investigate the involvement of AcCho in learning, at the level of single, identified brain neurons. We show that the feeding motor program (FMP) of the mollusc Pleurobranchaea is elicited by cholinergic activation of a population of feeding command interneurons in the brain, that the corresponding cholinergic response exhibits several characteristics of the vertebrate muscarinic response, and that this muscarinic-like response is str...

show abstract

“…The step-down apparatus derived from that described by Kubanis et al [1982] and consisted of a box constructed with plexiglass (23.5 cm long X 21 cm wide X 26 cm high). An aluminum platform (8 X 11 cm) was attached to one of the end walls approximately 7 cm above the floor of the apparatus.…”

Section: Materials and Methods Animalsmentioning

confidence: 99%

Chronic treatment with an acetylcholine synthesis precursor, alpha‐glycerylphosphorylcholine, alters brain parameters linked to cholinergic transmission and passive avoidance behavior

Govoni

López

Battaini

et al. 1992

Drug Development Research

View full text Add to dashboard Cite

The present study extends previous observations on the acute treatment with alpha-glycerylphosphorylcholine (GPC), a putative acetylcholine (ACh) precursor, and investigates the effect of chronic treatment with this drug on scopolamine-induced amnesia and on ACh release in the rat. The drug acutely administered antagonizes the amnesic effect of scopolamine (0.75 mg/kg s.c.) in passive avoidance experiments. The effect peaked at 600 mg/kg i.g. and lasted up to 30 hr. Potassium-stimulated release of ACh from slices of hippocampus and cerebral cortex was measured after various doses of GPC. The dose curve study indicated that GPC was able to increase ACh release in the hippocampus already at the dose of 75 mg/kg i.g. The maximum effect was obtained with 300 mg/kg i.g. (147% of the control values). The increase of the ACh release reached a maximum 3 hr following the administration, then declined toward control values. In the cortex, the effect was much less pronounced and shorter than in the hippocampus. The repeated (1 00 and 300 mg/kg i.g.; 22 days) GPC administration effectively antagonized scopolamine-induced amnesia, indicating that there was no tolerance to this effect of GPC. While both doses were behaviorally active only 300 mg/kg was able to increase ACh release from hippocampus ( + 271 %) and cortex ( + 57%). The data support the hypothesis that GPC improves behavioral performance in passive avoidance through an action on cholinergic transmission. On the other hand, it should be stressed that the action on ACh release is observed in a narrow time window in contrast to the long lasting effect on behavior. It is tempting to speculate that the effect on ACh may be related to cortical activation and important but not sufficient to explain the antagonism of scopolamine-induced amnesia. Along this line other mechanisms, possibly triggered by the action on ACh, may contribute to mediate the behavioral effect of GPC. o 1992 Wiley-Liss, Inc.

show abstract

Memory and postsynaptic cholinergic receptors in aging mice

Cited by 48 publications

References 21 publications

Environmental Enrichment Mitigates Cognitive Deficits in a Mouse Model of Alzheimer's Disease

Environmental Enrichment Mitigates Cognitive Deficits in a Mouse Model of Alzheimer's Disease

Cholinergic suppression: a postsynaptic mechanism of long-term associative learning.

Chronic treatment with an acetylcholine synthesis precursor, alpha‐glycerylphosphorylcholine, alters brain parameters linked to cholinergic transmission and passive avoidance behavior

Contact Info

Product

Resources

About