The role of the dorsal hippocampus in two versions of the touchscreen automated paired associates learning (PAL) task for mice

Abstract

RationaleThe CANTAB object-location paired-associate learning (PAL) test can detect cognitive deficits in schizophrenia and Alzheimer’s disease. A rodent version of touch screen PAL (dPAL) has been developed, but the underlying neural mechanisms are not fully understood. Although there is evidence that inactivation of the hippocampus following training leads to impairments in rats, this has not been tested in mice. Furthermore, it is not known whether acquisition, as opposed to performance, of the rodent version depends on the hippocampus. This is critical as many mouse models may have hippocampal dysfunction prior to the onset of task training.ObjectivesThe objectives of this study are to examine the effects of dorsal hippocampal (dHp) dysfunction on both performance and acquisition of mouse dPAL and to determine if hippocampal task sensitivity could be increased using a newly developed context-disambiguated PAL (cdPAL) paradigm.MethodsIn experiment 1, C57Bl/6 mice received post-acquisition dHp infusions of the GABA agonist muscimol. In experiment 2, C57Bl/6 mice received excitotoxic dHp lesions prior to dPAL/cdPAL acquisition.ResultsPost-acquisition muscimol dose-dependently impaired dPAL and cdPAL performance. Pre-acquisition dHp lesions had only mild effects on both PAL tasks. Behavioural challenges including addition of objects and degradation of the visual stimuli with noise did not reveal any further impairments.ConclusionsdPAL and cdPAL performance is hippocampus-dependent in the mouse, but both tasks can be learned in the absence of a functional dHp.

Fear Memory

“…Fear conditioning in particular relies on CS-US interactions in the DG and in the LA (295,328,350,448,574). After all, this fits better with the findings on humans with large bilateral temporal lobe lesions (493,589), specifically those with lesions restricted to the hippocampus (308,549,664,686), who have consistently been shown to have a general incapacity to retain new declarative memories of any kind, but to remember well memories acquired weeks or months before the lesion, and, importantly, do not show appreciable deficits in scene construction (of a picture they see) while consistently losing memory items relevant to that scene (308).…”

“…Current evidence does not support the view held over a long time that the hippocampus plays an almost exclusive role in contextual (240) or spatial learning (308,435), and the BLA has been shown to be involved in the consolidation of nonaversive memories as well (54, 56, 404). The hippocampus does play a key role in contextual and spatial learning, but it also is important or crucial for other types of learning.…”

Optimization of the touchscreen paired-associate learning (PAL) task for mice and its dorsal hippocampal dependency

“…dPAL has already been shown to be hippocampus dependent in rats and mice (Talpos et al 2009;Kim et al 2015). We found that the new protocol with overlearning did not affect the hippocampal dependency of this task.…”

“…In addition, this task was used to test the effect of antagonism of various Nmethyl-d-aspartate receptor subtypes in rats (Kumar et al 2015). The PAL task has also been used in mice in various studies (Bartko et al 2011b;Delotterie et al 2015;Kim et al 2015). To test if hippocampal neurogenesis is important for performing a spatial task, the PAL task was performed in mice with ablated neurogenesis (Clelland et al 2009).…”

“…Finally, we tested whether the PAL tasks with the new protocols are hippocampus dependent. The dPAL task has previously been shown to rely on hippocampal function in rats and mice (Talpos et al 2009;Kim et al 2015). By performing pharmacological experiments, we tested whether dPAL and sPAL with overlearning still require the function of the dorsal hippocampus (dHP), and the new 2-object sPAL task is also hippocampus dependent.…”