Elsevier

Brain Research Protocols

Volume 1, Issue 4, October 1997, Pages 331-338
Brain Research Protocols

Protocol
A rotating holeboard procedure for testing drug effects on spatial learning and memory in mice

https://doi.org/10.1016/S1385-299X(97)00007-XGet rights and content

Abstract

A procedure is described herein for evaluating drug effects on acquisition and retention of a spatial learning task in mice. The rotating holeboard apparatus is a rectangular open field containing four open holes arranged in either a four-corner or a row configuration. A mouse is trained to poke its head into a hole and retrieve a food reward from a `baited' hole which contains a reward on every trial. A massed trials protocol is used where mice are required to learn a reference (trial-independent) memory task in a single session. A retention test is administered 24 h after acquisition. Prominent distal cues are present in the testing room and reliance on proximal visual, olfactory, or tactile cues for locating the baited hole is precluded by rotating the maze on each trial.

Section snippets

Type of research

The rotating holeboard procedure has been used in our experiments to assess the effects of the non-competitive N-methyl-d-aspartate (NMDA) receptor antagonist, MK-801, on spatial reference memory acquisition and retention in mice. However, in theory it may be used to investigate the influence of a wide variety of experimental manipulations on spatial learning and memory in mice including:

  • Aging and development.

  • Behavioral teratologic effects.

  • Brain lesions.

  • Pharmacologic/neurotoxicologic effects,

Time required

The time required to complete an experiment depends on the design used. A pre- versus posttreatment design has been used in our experiments with mice to investigate both acute and chronic effects of drug treatment. The time needed to complete an experiment on acute drug effects using a basic pre- versus posttreatment design that includes two groups of mice (n=10) is described below.

Two weeks is typically devoted to habituating the mice to handling, the apparatus and the general experimental

Materials

  • Subjects. Male Harlan ICR mice that are between 2 and 3 months of age at the beginning of the study have been used in all our experiments. It seems likely that other ages and strains could be used with this procedure although this may necessitate changes in parameters such as time spent handling and habituating. Mice are maintained under standard housing conditions.

  • Apparatus. The rotating holeboard is a 47×47 cm square, enclosed by clear plastic sides, which has 16 holes, 2.54 cm in diameter,

Handling of subjects

Mice are handled and habituated daily for 3 min per day for 10 days in order to acquaint them with the experimenter, apparatus and general procedure.

Habituation

A. For the first 5 days of habituation, a mouse is handled by the experimenter for at least 1 min and then placed into the apparatus with all four holes covered and with pieces of Froot Loop scattered around the floor of the apparatus. A mouse is allowed to explore the apparatus and eat if it chooses during a 3 min period.

B. Food restriction

Results

We have used our rotating holeboard procedure to evaluate both the acute effects of a low dose (0.05 mg/kg) of MK-801 [1]as well as the chronic effects of a high dose (10 mg/kg) of MK-801 [11]. In both instances, the MK-801 treatment induced an impairment in acquisition performance when learning new information was required, although retention performance appeared to be unaffected by the drug. Obviously, different drugs and experimental manipulations may produce different effects. A more

Discussion

Our rotating holeboard procedure has proven to be a valuable tool for evaluating the acute and long-term effects of MK-801 on spatial learning and memory in the mouse. The procedure has been shown to be sensitive for documenting impairment in acquisition of new information following a very low dose of MK-801 which did not produce alterations in activity or sensorimotor disturbances [1]. Brosnan-Watters et al. [1]also reported that this dose of MK-801 did not affect retention of the task or

Quick procedure

A. Mice are handled and habituated for at least 2–3 weeks.

B. A mouse is removed from its home cage and placed in a holding cage for approx. 5 min before testing begins.

C. The mouse is placed in the start tube in the apparatus, the start tube is removed, and the experimenter starts a timer.

D. The mouse is allowed up to 3 min to find and consume the food reward (Froot Loop) in the one baited hole. A correct trial is scored when the mouse only pokes into the baited hole on a given trial. An

Essential literature references

Original papers: References [1]and [11].

Acknowledgements

This work was partially supported by NIH Grants AG 11355 and DA 05072. The authors thank Anthony Nardi for his assistance in some of the experiments cited in this report.

References (12)

  • G. Brosnan-Watters, D.F. Wozniak, A. Nardi, J.W. Olney, Acute behavioral effects of MK-801 in the mouse, Pharmacol....
  • S.E. File, A.G. Wardill, Validity of head-dipping as a measure of exploration in a modified hole-board,...
  • L. Froelich, A. Ding, S. Hoyer, Holeboard maze-learning deficits and brain monoaminergic neurotransmitter...
  • J.H. Hannigan Jr., R.L. Isaacson, The effects of Org 2766 on the performance of sham, neocortical, and...
  • R.L. McLamb, L.R. Williams, K.P. Nanry, W.A. Wilson, H. Tilson, MK-801 impedes the acquisition of a spatial memory task...
  • D.L. Murray, H.C. Fibiger, Pilocarpine and physostigmine attenuate spatial memory impairments produced by lesions of...
There are more references available in the full text version of this article.

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    This is done to minimalize differences in task complexity and task difficulty between the original task and the reversal task (Callaway et al., 2004; van der Staay, 1999). Brosnan-Watters and Wozniak (1997) and Brosnan-Watters et al. (1999) developed a rotating holeboard procedure, where the holeboard apparatus is rotated 90° after each trial. The location of baited holes, however, remains unchanged with respect to distal cues.

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    Hole board-learning paradigms were then used for rats by some researchers (Oades and Isaacson 1978; van der Staay et al. 1990a,b). It was later adapted to assess learning behavior in mice by retrieving a food pellet located in one hole out of four in a hole board task setup (Brosnan-Watters and Wozniak 1997; Brosnan-Watters et al. 1996). However, this task is not complex enough to assess reference and working memory.

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Present address: University of Northern Colorado, Psychology Department, Greeley, CO 80639, USA.

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