Ontogeny of contextual fear memory formation, specificity, and persistence in mice

Abstract

Pinpointing the precise age when young animals begin to form memories of aversive events is valuable for understanding the onset of anxiety and mood disorders and for detecting early cognitive impairment in models of childhood-onset disorders. Although these disorders are most commonly modeled in mice, we know little regarding the development of learning and memory in this species because most previous studies have been restricted to rats. Therefore, in the present study, we constructed an ontogenetic timeline of contextual fear memory ranging from infancy to adulthood in mice. We found that the ability of mice to form long-term context-shock associations emerged 13 -14 d of age, which is several days earlier than previously reported for rats. Although the ability to form contextual fear memories remained stable from infancy into adulthood, infant mice had shorter-lasting memories than adolescent and adult mice. Furthermore, we found that mice subjected to fetal alcohol exposure showed a delay in the developmental emergence of contextual fear memory, illustrating the utility of this ontogenetic approach in detecting developmental delays in cognitive function stemming from maladaptive early life experience.

Spatial discrimination reversal and incremental repeated acquisition in adolescent and adult BALB/c mice

“…The apparently off-task behavior may be analogous to off-task behavior in the SDR procedure inferred from adolescent omission errors. The differences seen with IRA contrast with studies reporting moderate or no differences between adolescents and adults on fear conditioning, water-maze performance, or acquisition of responding under variable interval schedules of reinforcement (Akers, et al, 2012; Broadwater & Spear, 2013; Kendig, et al, 2013). …”

Extinction of fear memory during development: lesson for a better exposure therapy?

“…Our group has observed elevated activity in the HPC during extinction retrieval in the juvenile mice, which suggested that HPC is likely to be functioning at this age [32]. This context-independent in cued fear memory extinction retrieval in the juvenile is consistent with previous findings [16,[33][34][35]. We also found that the output portion of the circuitry mediating extinction retrieval (IL to BLA) to be functional while the inputs portion (HPC to PFC) is not.…”

Extinction, reacquisition, and rapid forgetting of eyeblink conditioning in developing rats

“…Infantile amnesia was initially described in humans and refers to the inability to recall experiences that occurred over the first 3 -5 yr of life (for review, see Campbell and Spear 1972). Extensive systematic studies of infantile amnesia using nonhuman animals (typically mice or rats) in a variety of aversive learning paradigms have shown that younger animals forget faster than older animals (Campbell and Campbell 1962;Campbell 1967;Campbell et al 1968;Feigley and Spear 1970;Schulenburg et al 1971;Anderson and Riccio 2005;Akers et al 2012Akers et al , 2014Kim et al 2012). Consistent with the present findings, long-term retention deficits in young animals are shown even when immediate, or short-term retention is equivalent across ages, thus confirming that long-term retention deficits do not simply reflect poorer initial learning.…”