Elsevier

Neurobiology of Aging

Volume 11, Issue 5, September–October 1990, Pages 515-521
Neurobiology of Aging

A comparison of the working memory performances of young and aged mice combined with parallel measures of testing and drug-induced activations of septo-hippocampal and nbm-cortical cholinergic neurones

https://doi.org/10.1016/0197-4580(90)90112-DGet rights and content

Abstract

The spatial working memory performances of young (2 months) and aged (24–26 months) mice of the C57BL/6 strain were compared using a delayed nonmatching to place (DNMTP) protocol in an automated 8-arm radial maze. The aged mice were observed to exhibit a selective and interference-related memory deficit. Parallel neurochemical analysis of the activity of septo-hippocampal and nbm-cortical cholinergic neurones in vivo was conducted using measures of sodium-dependent high-affinity choline uptake. Results showed that whereas the level of cholinergic activity in both brain regions varied less than 10% between young and aged mice in quiet conditions (basal) the activation usually observed at 30-sec posttest (+20–25%) in young mice was greatly attenuated in the frontal cortex and almost totally absent in the hippocampus of aged mice. In view of these results a complementary experiment was carried out in order to test the intrinsic ability of septo-hippocampal cholinergic neurones to activate using acute injection of scopolamine (1 mg/kg IP 20 min) to both young and aged mice in quiet conditions. The drug injection resulted in a very large (+70%) increase in hippocampal high-affinity choline uptake and with amplitudes which did not vary significantly between young and aged subjects. These observations attest to a relatively well-preserved state of central cholinergic neurones and an intact capacity to activate normally when challenged pharmacologically in aged mice. The results strongly suggest that the loss of cholinergic activation and associated memory deficit in aged mice might rather be related to a hypofunction of phasically active transsynaptic processes which normally mediate the activation of these cholinergic pathways during memory testing.

References (41)

  • D. Galey et al.

    In vivo modulation of septo-hippocampal cholinergic activity in mice: relationships with spatial reference and working memory performance

    Behav. Brain Res.

    (1989)
  • J. Hardy et al.

    Transmitter deficits in Alzheimer's disease

    Neurochem. Int.

    (1985)
  • C.W. Harley

    A role for norepinephrine in arousal, emotion and learning?: limbic modulation by norepinephrine and the Kety hypothesis

    Prog. Neuropsychopharmacol. Biol. Psychiatry

    (1987)
  • P. Kubanis et al.

    Age-related behavioral and neurobiological changes: a review with emphasis on memory

    Behav. Neural Biol.

    (1981)
  • B. Marcyniuk et al.

    The topography of nerve cell loss from the locus coeruleus in elderly persons

    Neurobiol. Aging

    (1989)
  • A. Marighetto et al.

    Septal α-nor-adrenergic antagonism in vivo blocks the testing induced activation of septo-hippocampal cholinergic neurones and produces a concomitant deficit in working memory performance of mice

    Pharmacol. Biochem. Behav.

    (1989)
  • A.W. Procter et al.

    Topographical distribution of neurochemical changes in Alzheimer's disease

    J. Neurol. Sci.

    (1988)
  • G. Smith

    Animal models of Alzheimer's disease: experimental cholinergic denervation

    Brain Res. Rev.

    (1988)
  • A. Toumane et al.

    Differential hippocampal and cortical cholinergic activation during the acquisition, retention, reversal and extinction of a spatial discrimination in an 8-arm radial maze by mice

    Behav. Brain Res.

    (1988)
  • G. Wenk et al.

    Behavior alters the uptake of 3H-choline into acetylcholinergic neurons of the nucleus basalis magnocellularis and medial septal area

    Behav. Brain Res.

    (1984)
  • Cited by (33)

    • An update on the cognitive impact of clinically-used hormone therapies in the female rat: Models, mazes, and mechanisms

      2013, Brain Research
      Citation Excerpt :

      In animals, age-related spatial deficits become more pronounced as memory demand increases as well. This has been shown for age-associated interference-related deficits (Lebrun et al., 1990) and for memory capacity deficits (Aggleton et al., 1989; Bimonte-Nelson et al., 2003, 2004b; Bimonte et al., 2003). In general, working memory is distinguished from reference memory, which is necessary to remember information that remains constant over time (task-specific information, for discussion see Olton et al., 1979).

    • Assessment of spatial memory in mice

      2010, Life Sciences
      Citation Excerpt :

      The other advantage is that this test induces only a moderate level of stress (Hodges 1996). The radial maze has also been used to study age-related cognitive decline in various mouse models (Bernstein et al. 1985; Krazem et al. 2003; Lebrun et al. 1990; Lohmann and Riepe 2007; Marighetto et al. 2000; Nogues et al. 1996; Takahashi et al. 2009; Touyarot et al. 2002; Touzani et al. 2003). It has been suggested that mice use several types of information for task performance and as they mature they turn more often to distal cues for orientation (Chapillon et al. 1995).

    • Cholinergic system, rearing environment and trajectory learning during aging in mice

      2007, Physiology and Behavior
      Citation Excerpt :

      Spatial learning and memory alterations occur in aged humans [1–3] as well as in aged laboratory rodents [4–9]. Such dysfunctions have been correlated with functional or/and morphological changes in cholinergic structures in the central nervous system, such as the hippocampus [10], the dentate gyrus [11–13], the septal area [14], the septo-hippocampal system [15,16] and the basal forebain [10,17]. Moreover, there is evidence that deficits of spatial memory during aging are reduced, at least in part, by restoration of the cholinergic system functioning [18].

    • Models of anxiety: Responses of rats to novelty in an open space and an enclosed space

      2006, Behavioural Brain Research
      Citation Excerpt :

      Many laboratories around the world have been using the radial maze and the T-maze for assessing working memory [58,12,29,160,143,129,128,187] without raising comparable concerns as seen with the current models of anxiety. Our laboratory and others have used the radial maze for several years on flat open-arms with or without small ledges, and the results from lesions and drug studies were comparable to those using enclosed radial maze arms [52,54,53,99,97]. The strains of rats or mice and type of treatment have not been a major issue and were easily discernable.

    View all citing articles on Scopus
    View full text