Functional emergence of the hippocampus in context fear learning in infant rats

Abstract

The hippocampus is a part of the limbic system and is important for the formation of associative memories, such as acquiring information about the context (e.g. the place where an experience occurred) during emotional learning (e.g. fear conditioning). Here, we assess whether the hippocampus is responsible for pups’ newly emerging context learning. In all experiments, postnatal day (PN) 21 and PN24 rat pups received 10 pairings of odor-0.5mA shock or control unpaired odor-shock, odor only and shock only. Some pups were used for context, cue or odor avoidance tests, while the remaining pups were used for c-Fos immunohistochemistry to assess hippocampal activity during acquisition. Our results show that cue and odor avoidance learning were similar at both ages, while contextual fear learning and learning-associated hippocampal (CA1, CA3 and dentate gyrus) activity (c-Fos) only occurred in PN24 paired pups. To assess a causal relationship between the hippocampus and context conditioning, we infused muscimol into the hippocampus, which blocked acquisition of context fear learning in the PN24 pups. Muscimol or vehicle infusions did not affect cue learning or aversion to the odor at PN21 or PN24. The results suggest that the newly emerging contextual learning exhibited by PN24 pups is supported by the hippocampus.

Toward Understanding How Early-Life Stress Reprograms Cognitive and Emotional Brain Networks

“…This 'simulated poverty' induces stress in the dams (Ivy et al, 2008), and alters their behaviors (Ivy et al, 2008;Rice et al, 2008;Rincón-Cortés and Sullivan, 2014). This latter approach has provoked chronic unremitting stress in the pups (Gilles et al, 1996;Ivy et al, 2008;Rice et al, 2008;Moriceau et al, 2009;Raineki et al, 2010;Wang et al, 2011;Molet et al, 2014;Naninck et al, 2015). Notably, there is little evidence of physical stress of the pups, with no hypothermia and minimal weight changes .…”

Sensitive Periods in Affective Development: Nonlinear Maturation of Fear Learning

“…Whereas pre-weanling (P17) rats do not appear to extend learned fear associations to the broader surrounding environment, adult-like contextual fear conditioning emerges by P24. The emergence of contextual fear learning may reflect increased maturation of the hippocampus and its connections to the amygdala in the post-weanling animals (Raineki et al, 2010). Contextual fear memories in this juvenile, pre-adolescent phase are also labile, and undergo forgetting with the passage of time (Akers et al, 2014).…”

Postnatal development of the amygdala: A stereological study in rats

“…Both the amygdala and the hippocampus are involved in contextual conditioning (Anagnostaras et al, 2001;LeDoux, 2000b;Matus-Amat et al, 2007;Wiltgen et al, 2006). It has been shown that conditioning to a context emerges between 17 and 24 days of age in rats (Foster and Burman, 2010;Raineki et al, 2010;Rudy, 1993). Interestingly, however, whereas the hippocampus is not activated during such context conditioning in 21-day-old rats, it is activated in 24-dayolds (Raineki et al, 2010).…”

“…It has been shown that conditioning to a context emerges between 17 and 24 days of age in rats (Foster and Burman, 2010;Raineki et al, 2010;Rudy, 1993). Interestingly, however, whereas the hippocampus is not activated during such context conditioning in 21-day-old rats, it is activated in 24-dayolds (Raineki et al, 2010). The emergence of contextual conditioning is thus likely related to the maturation of both the hippocampus, which also exhibits a delayed developmental profile (Bekenstein and Lothman, 1991;Jabès et al, 2010Jabès et al, , 2011Nurse and Lacaille, 1999;Swann et al, 1990), and the basolateral complex of the amygdala, which likely is insufficiently mature to integrate such contextual information until the beginning of the third week of life.…”

“…Individual components of the fear response are thought to incorporate sequentially as animals mature, eventually giving rise to what are identified as mature fear behaviors (Wiedenmayer, 2009). Indeed, several studies have revealed that distinct fear behaviors emerge at different times during early postnatal life and continue to mature during late postnatal development (Blozovski and Cudennec, 1980;Bronstein and Hirsch, 1976;Chen et al, 2006;Collier et al, 1979;Foster and Burman, 2010;Hefner and Holmes, 2007;Hubbard et al, 2004;Ito et al, 2009;Kim and Richardson, 2007;Moriceau et al, 2004;Raineki et al, 2010;Rudy, 1993;Takahashi, 1992;Wiedenmayer andBarr, 1998, 2001a,b).…”