title: Hippocampal-dependent memory in the plus-maze discriminative avoidance task: The role of spatial cues and CA1 activity.
abstract: 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 (0.05 μg, 0.1 μg, and 0.2 μg) 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.
authors.affiliation: Memory Studies Laboratory, Department of Physiology, Universidade Federal do Rio Grande do Norte, Natal, RN, Brazil.
authors.forename: Anderson H F F
authors.initials: AH
authors.lastname: Leão
authors.affiliation: Laboratory of Behavioral Neuroscience, Department of Pharmacology, Universidade Federal de São Paulo, São Paulo, SP, Brazil.
authors.forename: André M
authors.initials: AM
authors.lastname: Medeiros
authors.affiliation: Memory Studies Laboratory, Department of Physiology, Universidade Federal do Rio Grande do Norte, Natal, RN, Brazil.
authors.forename: Gênedy K S
authors.initials: GK
authors.lastname: Apolinário
authors.affiliation: Memory Studies Laboratory, Department of Physiology, Universidade Federal do Rio Grande do Norte, Natal, RN, Brazil.
authors.forename: Alícia
authors.initials: A
authors.lastname: Cabral
authors.affiliation: Laboratory of Neuroscience and Bioprospecting of Natural Products, Department of Biosciences, Universidade Federal de São Paulo, Santos, SP, Brazil.
authors.forename: Alessandra M
authors.initials: AM
authors.lastname: Ribeiro
authors.affiliation: Memory and Cognition Studies Laboratory, Department of Psychology, Universidade Federal da Paraíba, João Pessoa, PB, Brazil.
authors.forename: Flávio F
authors.initials: FF
authors.lastname: Barbosa
authors.affiliation: Memory Studies Laboratory, Department of Physiology, Universidade Federal do Rio Grande do Norte, Natal, RN, Brazil; Laboratory of Behavioral Neuroscience, Department of Pharmacology, Universidade Federal de São Paulo, São Paulo, SP, Brazil. Electronic address: reginahsilva@gmail.com.
authors.forename: Regina H
authors.initials: RH
authors.lastname: Silva
mesh_terms: D000161:Acoustic Stimulation / Q000009:adverse effects; D000704:Analysis of Variance; D000818:Animals; D001362:Avoidance Learning / Q000187:drug effects / Q000502:physiology*; D056547:CA1 Region, Hippocampal / Q000187:drug effects / Q000502:physiology*; D003463:Cues; D004192:Discrimination, Psychological / Q000187:drug effects / Q000502:physiology*; D004305:Dose-Response Relationship, Drug; D058785:GABA-A Receptor Agonists / Q000378:metabolism / Q000494:pharmacology; D008297:Male; D018782:Maze Learning / Q000187:drug effects / Q000502:physiology*; D008568:Memory / Q000187:drug effects / Q000502:physiology*; D009118:Muscimol / Q000378:metabolism / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar
chemical_list: D058785:GABA-A Receptor Agonists; D009118:Muscimol
keywords: Anxiety; Aversive memory; Hippocampus; Muscimol; Plus-maze discriminative avoidance task