Development switch in neural circuitry underlying odor-malaise learning

Abstract

Fetal and infant rats can learn to avoid odors paired with illness before development of brain areas supporting this learning in adults, suggesting an alternate learning circuit. Here we begin to document the transition from the infant to adult neural circuit underlying odor-malaise avoidance learning using LiCl (0.3 M; 1% of body weight, ip) and a 30-min peppermint-odor exposure. Conditioning groups included: Paired odor-LiCl, Paired odor-LiCl-Nursing, LiCl, and odor-saline. Results showed that Paired LiCl-odor conditioning induced a learned odor aversion in postnatal day (PN) 7, 12, and 23 pups. Odor-LiCl Paired Nursing induced a learned odor preference in PN7 and PN12 pups but blocked learning in PN23 pups. 14C 2-deoxyglucose (2-DG) autoradiography indicated enhanced olfactory bulb activity in PN7 and PN12 pups with odor preference and avoidance learning. The odor aversion in weanling aged (PN23) pups resulted in enhanced amygdala activity in Paired odor-LiCl pups, but not if they were nursing. Thus, the neural circuit supporting malaise-induced aversions changes over development, indicating that similar infant and adult-learned behaviors may have distinct neural circuits.Animals rapidly learn to avoid tastes, smells, and textures of foods associated with malaise, and this learning process produces conditioned taste and odor aversions (Garcia et al. 1966(Garcia et al. , 1974 Best 1992, 1993). This learning has been demonstrated early in development, including both the embryonic day (ED) 18 rat and mouse fetuses, with retention time lasting weeks Haroutunian and Campbell 1979;Smotherman 1982;Stickrod et al. 1982b;Rudy and Cheatle 1983; Robinson 1985, 1990;Alleva and Calamandrei 1986;Molina et al. 1986;Hoffmann et al. 1987Hoffmann et al. , 1990Miller et al. 1990;Hunt et al. 1991Hunt et al. , 1993Abate et al. 2001;Richardson and McNally 2003;Gruest et al. 2004a). Taste/odor aversion acquisition shows some specific differences between pups and adults. First, nursing during acquisition disturbs taste-aversion learning, although this diminishes as pups approach weanling (Martin and Alberts 1979;Gubernick and Alberts 1984;Melcer et al. 1985;Kehoe and Blass 1986). Second, in contrast to the long temporal parameters permitted between the odor/taste (conditioned stimulus, CS) and illness (unconditioned stimulus, US) in adult taste aversion, the temporal constraints between the CS and the malaise producing US for pup learning are very limited (Rudy and Cheatle 1983;Kraemer et al. 1988Kraemer et al. , 1989Hoffmann et al. 1990Hoffmann et al. , 1991.There is evidence that the neural basis of odor/taste aversion learning may change over development. In adults, the amygdala is thought to support taste-aversion learning, though there are discrepancies in the literature (Nachman and Ashe 1974;Burt and Smotherman 1980;Dunn and Everitt 1988;Yamamoto and Fujimoto 1991;Kesner et al. 1992;Yamamoto et al. 1994;Bures et al. 1998;Schafe et al. 1998;Sakai and Yamamoto 1999;Wilkins and Bernstein 2006). When the taste and smell component...

The temporal dynamics of consolidation and reconsolidation decrease during postnatal development

“…They show that conditioning induces an odor aversion in P7, P12, and P23 pups and that the aversion is independent of amygdala in P7 and P12 pups, but implicates it in P23 pups. The neural circuit supporting the same learned behavior may be different in the pup and the weanling rat (Shionoya et al 2006). Such a change in the substrates of learning may involve differences in memory processing and modify its duration.…”

“…Research on cognitive development has demonstrated very early learning capacities in vertebrates; different kinds of associative learning may be acquired by neonates and even by the fetus (Smotherman et al 1982;Kehoe and Blass 1986;Cheslock et al 2000;Sullivan 2001;Smotherman 2002;Gruest et al 2004a;Shionoya et al 2006). Some of these early acquisitions have been shown to be retained in the long term, but the characteristics of long-term memory in the course of development are still poorly known, particularly concerning its stabilization.…”

Postnatal development of the amygdala: A stereological study in rats

“…At P12-13, the three conditions induce odor avoidance, but the basolateral complex of the amygdala is activated only when the odor is paired with a 0.5-mA shock but not when a stronger, 1.2-mA shock or LiCl injection is administered. In contrast, at P23-24, the basolateral complex is activated under all three conditions (Raineki et al, 2009;Shionoya et al, 2006). Similarly, at P14, exposure to a male rat induces c-fos expression in the medial nucleus of the amygdala, but not in the lateral nucleus, whereas, at P18, c-fos expression is observed in both the medial and the lateral nuclei (Chen et al, 2006;but see Wiedenmayer and Barr, 2001a).…”

“…For example, at P7-8, a 0.5-mA or a 1.2-mA shock or LiCl injection induces odor preference or avoidance without activation of the basolateral complex of the amygdala as revealed by 2-deoxyglucose uptake (Raineki et al, 2009;Shionoya et al, 2006). At P12-13, the three conditions induce odor avoidance, but the basolateral complex of the amygdala is activated only when the odor is paired with a 0.5-mA shock but not when a stronger, 1.2-mA shock or LiCl injection is administered.…”

Ontogeny of odor-LiCl vs. odor-shock learning: Similar behaviors but divergent ages of functional amygdala emergence

“…At weaning (PN23-24), all learning paradigms produced learning-associated changes in the posterior piriform cortex and basolateral amygdala complex. These results suggest at least two basic principles of the development of the neurobiology of learning: (1) Learning that appears similar throughout development can be supported by neural systems showing very robust developmental changes, and (2) the emergence of amygdala function depends on the learning protocol and reinforcement condition being assessed.Even in utero, infant rats rapidly learn to avoid odors paired with malaise (LiCl) as expressed by learning an odor aversion (Garcia et al 1966(Garcia et al , 1974Hennessey et al 1976;Haroutunian and Campbell 1979;Smotherman 1982;Stickrod et al 1982;Rudy and Cheatle 1983;Kucharski and Spear 1984;Smotherman and Robinson 1985, 1990;Alleva and Calamandrei 1986;Miller et al 1990b; Best 1992, 1993;Richardson and McNally 2003;Gruest et al 2004;Shionoya et al 2006). In contrast to adult odor-LiCl learning, which relies on the amygdala (Touzani and Sclafani 2005), this early-life, odoraversion learning relies on the olfactory bulb until the pup approaches weaning age, when the amygdala is incorporated into the learning circuitry (Shionoya et al 2006).…”