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-0.5mA 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-0.5mA 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.

Learning not to Fear: Neural Correlates of Learned Safety

“…Moreover, a reduction of stressor-induced c-Fos-immunoreactive cells, indicating neural activity induced by safety signals, was also observed in another study on basolateral amygdala (BLA), which also reports a similar effect of learned safety in the ventrolateral region of the bed nucleus of stria terminalis (BNSTlv) (Christianson et al, 2008;Christianson et al, 2011). Furthermore, deficient pairedpulse inhibition in the amygdala and the piriform cortex induced by infant odor-shock pairing is restored in the presence of the infant odor functioning as a safety signal (Sevelinges et al, 2011). Thus, the amygdala most likely constitutes the prime site for both acquisition and consolidation of learned safety subserved by specific molecular events reflected in safety learning-induced gene expression in the BLA (discussed below).…”

“…Neural correlates of learned safety E Kong et al limited to the inhibition of the learned fear induced by a specific CS, learned safety involves a wider spectrum of behavioral responses, including the reduction of innate fear, the potential of the stimulus to be transferred and to elicit reward-and antidepressant-like effects (Pollak et al, 2008;Rogan et al, 2005;Sevelinges et al, 2011). Interestingly, however, both paradigms have an important role as animal models of PTSD, by reproducing separate symptomatic features forming part of the clinical diagnostic picture of the disorder and presumably reflecting distinct endophenotypes (see below for detailed discussion).…”

“…Interestingly, it was found that although learned safety served as a behavioral antidepressant in two animal tests for depression (ie the forced-swim test and the sucrose preference test) (Pollak et al, 2008;Sevelinges et al, 2011)-in a manner comparable to the effect achieved by treatment with pharmacological antidepressants (such as the selective serotonin reuptake inhibitor fluoxetine)-alternative molecular signal-transduction pathways seemed to be mediating its antidepressant activity. Although most frequently described antidepressant drugs act upon the monoaminergic systems, specifically the serotonergic system (such as fluoxetine), learned safety seems to involve modulation of dopaminergic and neuropeptidergic signaling, specifically dopamine type 2 receptors and substance P together with other molecules previously implicated in stress response and the pathogenesis of depression, including preproenekphalin1 and prodynorphin (Pollak et al, 2008).…”

Differential involvement of amygdala and cortical NMDA receptors activation upon encoding in odor fear memory

“…Recently, Luna and Morozov (2012) reported that the pPC differentially responds to amygdaloid versus cortical inputs by utilizing distinct local microcircuits. The pPC is thus an ideal locus to combine the sensory characteristics of the stimulus with its affective learned value transmitted by the BLA to keep the trace of this emotional olfactory memory as suggested by previous studies (Sevelinges et al 2004(Sevelinges et al , 2008(Sevelinges et al , 2011Barnes et al 2011;Chen et al 2011).…”

“…Recently, Luna and Morozov (2012) reported that the pPC differentially responds to amygdaloid versus cortical inputs by utilizing distinct local microcircuits. The pPC is thus an ideal locus to combine the sensory characteristics of the stimulus with its affective learned value transmitted by the BLA to keep the trace of this emotional olfactory memory as suggested by previous studies (Sevelinges et al 2004(Sevelinges et al , 2008(Sevelinges et al , 2011Barnes et al 2011;Chen et al 2011).Most studies questioning the role of sensory cortices in fear conditioning have used auditory stimuli. These studies revealed that the lesion of auditory sensory cortices do not prevent the acquisition of auditory fear conditioning, thus arguing against their involvement in the learning (Campeau and Davis 1995; Armony et al 1997).…”