Effects of Early Life Adversities upon Memory Processes and Cognition in Rodent Models Joelma Alves, ay Natividade de Sa´ Couto-Pereira, by Randriely Merscher Sobreira de Lima, bà Jorge Alberto Quillfeldt b,c and Carla Dalmaz a,b * a Programa de Po´ s-graduac¸a˜o em Cieˆncias Biolo´gicas: Bioquı´mica, Departamento de Bioquı´mica, Instituto de Cieˆncias Ba´sicas da Sau´ de, Universidade Federal do Rio Grande do Sul - UFRGS, Porto Alegre, RS, Brazil b Programa de Po´ s-graduac¸a˜o em Neurocieˆncias, Instituto de Cieˆncias Ba´sicas da Sau´ de, Universidade Federal do Rio Grande do Sul - UFRGS, Porto Alegre, RS, Brazil c Departamento de Biofı´sica, Instituto de Biocieˆncias, Universidade Federal do Rio Grande do Sul - UFRGS, Porto Alegre, RS, Brazil Abstract—Exposure to stressors in early postnatal life induces long-lasting modifications in brain function. This plasticity, an essential characteristic of the brain that enables adaptation to the environment, may also induce impairments in some psychophysiological functions, including learning and memory. Early life stress (ELS) has long-term effects on the hypothalamic–pituitary–adrenal axis response to stressors, and has been reported to lead to neuroinflammation, altered levels of neurotrophic factors, modifications in neurogenesis and synaptic plasticity, with changes in neurotransmitter systems and network functioning. In this review, we focus on early postnatal stress in animal models and their effects on learning and memory. Many studies have reported ELS- induced impairments in different types of memories, including spatial memory, fear memory, recognition (both for objects and social) memory, working memory and reversal learning. Studies are not always in agreement, however, no effects, or sometimes facilitation, being reported, depending on the nature and intensity of the early intervention, as well as the age when the outcome was evaluated and the sex of the animals. When considering processes occurring after consolidation, related with memory maintenance/persistence or transformation, there are a very reduced number of reports. Future studies addressing the mechanisms underlying memory changes for ELS should shed some light on the understanding of the different effects induced by stressors of different types and intensities on cognitive functions. This article is part of a Special Issue entitled: In memory of Ivan Izquierdo South American pioneer of the Neuroscience of Memory Temporal dynamics and molecular mechanisms. Ó 2022 IBRO. Published by Elsevier Ltd. All rights reserved. Key words: maternal separation, limited bedding and nesting, early handling, hypothalamus–pituitary–adrenal axis, early life str- ess, age. INTRODUCTION Ivan A. Izquierdo (1937–2021) was a leading scientist in the study of the neurobiology of learning and memory, particularly in South America, where he trained dozens of scientists. Of particular importance for this review are his studies concerning the effects of stress exposure on memory. Since the sixties (Vasquez et al., 1967) he pointed to the importance of stress hormones and stress situations for both memory consolidation and memory retrieval and studied how stress hormones released dur- ing these memory phases (adrenocorticotropin hormone – ACTH, epinephrine and vasopressin) could affect per- formance (e.g., Dias and Izquierdo, 1983; Izquierdo et al., 1988a,b, 2002). He considered that memory could be affected by other experiences, that could become incorporated into the experiences leading to a memory, altering their content (Izquierdo et al., 1988b; Mello et al., 2008). He also studied how early adverse experi- ences could affect memory later in life (Benetti et al., 2009; 2012). Here, we review some evidence related to the effects of early stress exposure on memory in distinct animal models. https://doi.org/10.1016/j.neuroscience.2022.04.023 0306-4522/Ó 2022 IBRO. Published by Elsevier Ltd. All rights reserved. * Correspondence to: C. Dalmaz, Programa de Po´s-graduac¸a˜o em Cieˆncias Biolo´gicas: Bioquı´mica, Departamento de Bioquı´mica, Instituto de Cieˆncias Ba´sicas da Sau´de, Universidade Federal do Rio Grande do Sul - UFRGS, Porto Alegre, RS, Brazil. E-mail addresses: quillfe@ufrgs.br (J. A. Quillfeldt), cdalmaz@ufrgs. br (C. Dalmaz). y Both authors contributed equally. à Present address: Department of Psychiatry, Faculty of Medicine, McGill University, Montreal, QC, Canada. Abbreviations: ACTH, adrenocorticotropin hormone; ELS, Early life stress; ESI, early social isolation; HPA, hypothalamus–pituitary–adre nal axis; LBN, limited bedding and nesting; MD, maternal deprivation; MS, maternal separation; MWM, Morris Water Maze; NOL, novel object location task; PFC, prefrontal cortex; PND, postnatal day; LTM, lont-term memory; STM, short-term memory. NEUROSCIENCE REVIEW J. Alves et al. / Neuroscience 497 (2022) 282–307 282