The neurobiological basis of spontaneous alternation

doi:10.1016/S0149-7634(01)00041-0

Neuroscience & Biobehavioral Reviews

Volume 26, Issue 1, January 2002, Pages 91-104

https://doi.org/10.1016/S0149-7634(01)00041-0 Get rights and content

Abstract

When placed in a T-maze, rats or mice possess a strong tendency of alternating arm choices on successive trials. The exploration of novel environmental stimuli is dependent on the integrity of limbic and non-limbic pathways, including the basal forebrain, the hippocampus, the thalamus, the prefrontal cortex, and the dorsal striatum, as well as the vestibular system and cerebellum. Neurochemical pathways using acetylcholine, gamma-amino-butyric acid, and dopamine in the septum and hippocampus have been implicated in the exploration of novel maze arms. In addition to the delineation of interactions between neurotransmitters, the spontaneous alternation test is sensitive to the consequences of normal and pathological aging.

Introduction

Spontaneous alternation is a measure of exploratory behavior, most often evaluated in rodents [43], [44], but also in other species [21], [61]. On the first trial, a mouse or rat is typically placed in the stem of a T- or Y-maze and is allowed to enter one of two maze arms. On the second trial, the animal has a choice of either repeating the same response or alternating. A plus-maze may also be used for spontaneous alternation testing [164], in which the animal is released from either the top or the bottom stem, permitting the choice of alternating either between arm choices or between left/right body turns. The same information is obtained by turning the maze at an angle of 180° [16]. A fourth type of maze used is the 8-arm radial maze, which increases the possibility of alternations from two to eight choices [24].

Rats and mice normally alternate at levels significantly above chance [43], [44], as do cats [61] and chickens [21], indicating their willingness to explore novel environmental stimuli. However, spontaneous alternation is dependent on optimal levels of anxiety, as the rates decrease in mice with higher levels of anxiety [12], [125]. Spontaneous alternation is also dependent on spatial memory capacity. By varying the length of the retention interval, this test estimates the strength of spatial working memory [80], [94].

Section snippets

Forced versus free choice trials and exposure times

Two paradigms have been used for testing spontaneous alternation: a forced-trial or a free-trial procedure (Fig. 1). In the forced-trial method, one of the maze arms is blocked during the first trial, whereas with the free-trial method, the animal may choose either arm. The alternation rate is generally higher with the forced-trial as opposed to the free-trial procedure, as animals are more willing to select the unfamiliar arm of a maze when previously forced to enter a maze arm [43], [44]. One

Hippocampus and temporal neocortex

It has been consistently demonstrated that, by comparison to sham-operated controls, spontaneous alternation rates in the T-maze free-trial procedure, decrease in rats with surgically-induced lesions of the hippocampus [84], [88], [121], [154], [166]. The impairment of spontaneous alternation scores by neurochemical lesions of the hippocampus indicates that this lesion effect is probably caused by the loss in neuronal bodies [18]. On the other hand, no deficit was reported when the forced-trial

Acetylcholine

The role of acetylcholine on spontaneous alternation has been examined with drugs that decrease synaptic transmission, such as scopolamine and atropine, cholinergic receptor antagonists of the muscarinic type, as well as drugs that increase synaptic transmission, such as carbachol, a cholinergic receptor agonist, and physostigmine, an inhibitor of the catabolizing enzyme, acetylcholinesterase. Spontaneous alternation rates of rats injected peripherally with scopolamine have often been shown to

Aging

Cross-sectional studies of rat populations have shown decrease in spontaneous alternation rates as a function of aging. For example, the spontaneous alternation rates of 22-month-old rats were found to be lower than that of 2-month-old rats [201]. This impairment was exacerbated at longer retention intervals, indicating an increased vulnerability to spatial memory deficits [206]. However, no deficit in spontaneous alternation was seen in other rats [11], [17], probably as a result of genetic

Transgenic mouse models of Alzheimer's disease

Spontaneous alternation has been tested in several murine models of Alzheimer's disease, the most prevalent cause of dementia in the elderly. Because patients with Alzheimer's disease display a lack of initiative in addition to anterograde amnesia, it is of interest to examine how closely the mouse model resembles human symptomatology. Mice overexpressing the neuron-specific 695 isoform of either the murine β-amyloid precursor protein (βAPP) gene or the human βAPP gene with a 3′-myc tag had

Conclusions

Spontaneous alternation is sensitive to a wide variety of brain lesions and to the administration of numerous neuromodulators. The accumulated knowledge on this topic will eventually permit an in-depth description of the chemical neuroanatomy underlying this behavior. Table 2 illustrates a summary of those neuromodulators implicated in the limbic system, including the hippocampus, septum, amygdala, and nucleus accumbens. Further experiments, in particular with the intracerebral administration

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ReviewThe neurobiological basis of spontaneous alternation

Abstract

Introduction

Section snippets

Forced versus free choice trials and exposure times

Hippocampus and temporal neocortex

Acetylcholine

Aging

Transgenic mouse models of Alzheimer's disease

Conclusions

Behav Brain Res

Brain Res Bull

Behav Brain Res

Pharmacol Biochem Behav

Behav Brain Res

Brain Res

Behav Brain Res

Behav Neural Biol

Behav Brain Res

Pharmacol Biochem Behav

Behav Brain Res

Pharmacol Biochem Behav

Brain Res

Pharmacol Biochem Behav

Behav Brain Res

Behav Brain Res

Pharmacol Biochem Behav

Pharmacol Biochem Behav

Behav Brain Res

Behav Biol

Neuropharmacology

Behav Brain Res

Brain Res

Physiol Behav

Eur J Pharmacol

Physiol Behav

Brain Res

Neurosci Lett

Brain Res

Eur J Pharmacol

Physiol Behav

Behav Brain Res

Neuron

Behav Brain Res

Pharmacol Biochem Behav

Exp Neurol

Brain Res

Behav Brain Res

Pharmacol Biochem Behav

Brain Res Rev

Brain Res

Physiol Behav

Brain Res

Behav Brain Res

Brain Res

Spontaneous alternation and d-amphetamine

Psychonomic Sci

Hippocampal formation

Memory deficits associated with senescence: a neurophysiological and behavioral study in the rat

J Comp Physiol Psychol

Comparison of the effects of frontal and caudate lesions on delayed response and alternation in monkeys

J Comp Physiol Psychol

Impairment of spontaneous alternation behavior in sequential test procedures following mamillary body lesions in mice: evidence for time-dependent interference-related memory deficits

Behav Neurosci

Review
The neurobiological basis of spontaneous alternation