Developmental changes in olfactory behavior and limbic circuitry.

The olfactory system of infant rats is not an immature version of the adult system but is organized to ensure infants form the attachment to the caregiver necessary for survival. We study a sensitive period during the first nine days of life when rat pups have unique learning abilities that ensure pups quickly and reliably learn a preference for the maternal odor that underlies pup orientation to the mother and nursing. There are two unique aspects of this early learning. First, neonatal rat pups have an increased ability to acquire odor preferences. It produces corresponding metabolic and anatomical changes in the olfactory bulb that is supported by norepinephrine from the hyperfunctioning neonatal locus coeruleus (Sullivan, 2003; Moriceau and Sullivan, 2004a). The neonatal learned odor preference and the associated olfactory bulb changes are maintained into adulthood. Secondly, which is the focus of this paper, neonatal pups have a decreased ability to acquire learned odor aversions (Sullivan et al., 1986, 2000; Camp and Rudy, 1988), presumably due to lack of amygdala participation in aversive conditioning (assessed by 2-DG; Sullivan et al., 2000). Specifically, during the sensitive period, a novel odor paired with painful 0.5mA shock produces a subsequent odor preference in pups. [Neonatal (1.2mA; Spear and Rudy, 1991).] It should be noted that pups of this age feel pain (Haroutunian and Campbell, 1979; Barr, 1995) and do not show a preference for the shock, only the odor. We also find that the amygdala, a brain area necessary for adult odor–shock fear conditioning (Fanselow and Gale, 2003; Maren, 2003), does not participate in this shock-induced odor preference (Sullivan et al., 2000). We suggest that the failure of the amygdala to participate in the neonatal sensitive period odor shock conditioning results in the odor preference. On postnatal day (PN) 10, when walking emerges (Bolles and Woods, 1964), naïve pups easily learn to avoid odors paired with shock and the amygdala participates in this conditioning (Sullivan et al., 2000). We suggest that the functional emergence of the amygdala in odor shock conditioning at PN10 permits pups to learn a shock-induced odor aversion using a fear conditioning paradigm. Thus, during the sensitive period the neonate appears to use a unique neural circuitry for learning. Considering structures that support adult learning are probably not functional in the neonate (amygdala, hippocampus, cerebellum, frontal cortex) and connections between these areas are still maturing, it is not surprising that neonatal pups are using a different circuit (Verwer et al., 1996; Nair and Gonzalez-Lima, 1999; Stanton, 2000; reviewed in Sullivan, 2003).