Hippocampal-dependent memory in the plus-maze discriminative avoidance task: The role of spatial cues and CA1 activity

•Distal and proximal cues are required to retrieve the discriminative avoidance task.•Proximal cues are more salient than distal cues to spatial discrimination.•Anxiolytic and amnestic effects of muscimol on CA1 are independent.•Muscimol dose-dependently impaired the performance in the avoidance tas...

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Published in:	Behavioural brain research Vol. 304; pp. 24 - 33
Main Authors:	Leão, Anderson H.F.F., Medeiros, André M., Apolinário, Gênedy K.S., Cabral, Alícia, Ribeiro, Alessandra M., Barbosa, Flávio F., Silva, Regina H.
Format:	Journal Article
Language:	English
Published:	Netherlands Elsevier B.V 01-05-2016
Subjects:	Acoustic Stimulation - adverse effects Analysis of Variance Animals Anxiety Aversive memory Avoidance Learning - drug effects Avoidance Learning - physiology CA1 Region, Hippocampal - drug effects CA1 Region, Hippocampal - physiology Cues Discrimination (Psychology) - drug effects Discrimination (Psychology) - physiology Dose-Response Relationship, Drug GABA-A Receptor Agonists - metabolism GABA-A Receptor Agonists - pharmacology Hippocampus Male Maze Learning - drug effects Maze Learning - physiology Memory - drug effects Memory - physiology Muscimol Muscimol - metabolism Muscimol - pharmacology Plus-maze discriminative avoidance task Rats Rats, Wistar EPM DG TOA TAV Muscimol PMDAT CA1 CA3 AV BLA GABA Anxiety Plus-maze discriminative avoidance task Hippocampus Aversive memory
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Summary:	•Distal and proximal cues are required to retrieve the discriminative avoidance task.•Proximal cues are more salient than distal cues to spatial discrimination.•Anxiolytic and amnestic effects of muscimol on CA1 are independent.•Muscimol dose-dependently impaired the performance in the avoidance task.•Limited CA1 activity is required to learn the discriminative avoidance task. The plus-maze discriminative avoidance task (PMDAT) has been used to investigate interactions between aversive memory and an anxiety-like response in rodents. Suitable performance in this task depends on the activity of the basolateral amygdala, similar to other aversive-based memory tasks. However, the role of spatial cues and hippocampal-dependent learning in the performance of PMDAT remains unknown. Here, we investigated the role of proximal and distal cues in the retrieval of this task. Animals tested under misplaced proximal cues had diminished performance, and animals tested under both misplaced proximal cues and absent distal cues could not discriminate the aversive arm. We also assessed the role of the dorsal hippocampus (CA1) in this aversive memory task. Temporary bilateral inactivation of dorsal CA1 was conducted with muscimol (0.05μg, 0.1μg, and 0.2μg) prior to the training session. While the acquisition of the task was not altered, muscimol impaired the performance in the test session and reduced the anxiety-like response in the training session. We also performed a spreading analysis of a fluorophore-conjugated muscimol to confirm selective inhibition of CA1. In conclusion, both distal and proximal cues are required to retrieve the task, with the latter being more relevant to spatial orientation. Dorsal CA1 activity is also required for aversive memory formation in this task, and interfered with the anxiety-like response as well. Importantly, both effects were detected by different parameters in the same paradigm, endorsing the previous findings of independent assessment of aversive memory and anxiety-like behavior in the PMDAT. Taken together, these findings suggest that the PMDAT probably requires an integration of multiple systems for memory formation, resembling an episodic-like memory rather than a pure conditioning behavior. Furthermore, the concomitant and independent assessment of emotionality and memory in rodents is relevant to elucidate how these memory systems interact during aversive memory formation. Thus, the PMDAT can be useful for studying hippocampal-dependent memory when it involves emotional content.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23
ISSN:	0166-4328 1872-7549
DOI:	10.1016/j.bbr.2016.02.012