Adult depression-like behavior, amygdala and olfactory cortex functions are restored by odor previously paired with shock during infant's sensitive period attachment learning

Abstract

Maltreatment from the caregiver induces vulnerability to later life psychopathologies, yet attraction and comfort is sometimes provided by cues associated with early life maltreatment. We used a rat model of early life maltreatment with odor-0.5 mA shock conditioning to produce depressive-like behaviors and questioned whether stimuli associated with maltreatment would restore emotional neurobehavioral function to control levels. Pups received daily novel odor-0.5 mA shock conditioning from postnatal day 8 to 12. This procedure produces a new maternal odor that controls pups' attachment behaviors. In adulthood, either with or without the infant odor, animals received a Forced Swim Test, Sucrose Preference Test or assessment of amygdala and olfactory system functioning using field potential signal evoked by olfactory bulb paired-pulse electrical stimulation. Following neonatal odor-shock pairings, but not unpaired controls, adults without the odor present showed increased depression-like behavior in the Forced Swim Test and Sucrose Preference Test and a deficit in paired-pulse inhibition in amygdala and piriform (olfactory) cortex. All effects were brought to control levels when the infant conditioned odor was presented during behavioral and neural tests. The ability of cues associated with early life maltreatment to normalize behavior and amygdala activity suggests these cues provide adaptive value in adulthood.

Keywords: amygdala; depression; infant experiences; odor-shock pairing; plasticity; safety signal.

Graphical abstract

Fig. 1

Effects of shocks on behavioral activation and vocalizations in pups. The presentation of a 0.5 mA shock induces a similar level of behavioral activation (A) and vocalizations (B) in Paired and Unpaired odor–shock animals during the conditioning session. During this session, Odor-only animals exhibited none of these two parameters. *: significant difference from all other groups (p < 0.05).

Fig. 2

Acquisition curve to CS odor presentation during conditioning in infancy. During odor–shock conditioning, Paired animals exhibited a progressive increase of odor-induced behavioral activation. Animals from control groups (Unpaired and Odor-only) showed no behavioral activation in response to odor presentation. *: significant difference from all other groups (p < 0.05).

Fig. 3

Odor–shock pairing produced an odor similar in quality to maternal odor since it produced an odor preference/approach to the odor, as well as supporting nipple attachment. Paired animals learned the odor that was expressed as (A) an odor preference as indicated by an approach to the odor in a Y-maze and (B) support of nipple attachment on a mother with the natural maternal odor removed. Unpaired and Odor-only control animals exhibited no learning in either test. *: significant difference from all other groups (p < 0.05).

Fig. 4

Infant odor attraction is maintained at adulthood. During the adult Y-maze test, Infant Paired, but not Infant Unpaired animals chose preferentially the arm containing the odor paired with shock during infancy. *: significant intergroup difference (p < 0.05).

Fig. 5

Effects of infant odor–shock experience on adult depression-like behavior as assessed in the Forced Swim Test and Sucrose Preference Test. Adult animals with Infant Paired experience exhibited a lower latency to immobility (A), spent more time immobile (B) and exhibited an anhedonia in the Sucrose Preference Test (C). However, they behaved similarly to control animals when the infant learned peppermint odor was presented. *: significant intergroup differences (p < 0.001).

Fig. 6

Effects of the novel citral odor on adult depression-like behavior as assessed in the Forced Swim Test and Sucrose Preference Test. Adult animals with Infant Paired experience exhibited a lower latency to immobility, spent more time immobile (A), and exhibited an anhedonia in the Sucrose Preference Test (B). However, contrary to the infant odor paired with shock, the novel citral odor failed to restore the behavior to control level.

Fig. 7

Effects of infant odor–shock experience on field potential responses recorded in the anterior (aPC) and posterior (pPC) piriform cortex, cortical (CoA) and basolateral (BLA) amygdala in response to paired-pulse electrical stimulation of the olfactory bulb, using a 20 ms inter-pulse interval. (A) Representative individual mean signals (n = 12 sweeps) recorded in the BLA in response to the conditioning (first) and test (second) pulses delivered to the olfactory bulb with or without the infant learned odor present. The signal induced by the conditioning pulse (dotted line) is superimposed on the signal resulting from the test pulse. (B) Mean paired-pulse ratios (mean test signal amplitude/mean conditioning signal amplitude ± SEM) obtained in the different experimental groups, in the four recording sites. A ratio <1 characterizes paired-pulse inhibition, whereas a ratio >1 corresponds to paired-pulse facilitation. Infant Paired animals exhibited a deficit in paired-pulse inhibition compared to control animals in the pPC, CoA and BLA. However, presentation of the infant learned peppermint odor brought paired-pulse ratios to control values. *: significant intergroup differences (p < 0.05).