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A Lateralized Odor Learning Model in Neonatal Rats for Dissecting Neural Circuitry Underpinning Memory Formation
Published on: August 18, 2014
Corticosterone controls the developmental emergence of fear and amygdala function to predator odors in infant rat
Stephanie Moriceau1, Tania L Roth, Terri Okotoghaide
1Department of Zoology, University of Oklahoma, 730 Van Vleet Oval, Norman, OK 73019, USA. smoriceau@ou.edu
Insights
In infant rats, corticosterone (CORT) levels influence the development of fear responses. Early CORT increases can trigger fear and amygdala activity, while low CORT protects against fear.
Area of Science:
- Neuroscience
- Developmental Biology
- Endocrinology
Background:
- Fear responses, like freezing, develop later in altricial species.
- In infant rats, fear to predator odors emerges around postnatal day 10, coinciding with increased corticosterone (CORT) and amygdala function.
Purpose of the Study:
- To investigate the hypothesis that rising CORT levels drive amygdala activity and the emergence of fear expression in infant rats.
- To assess the relationship between fear, amygdala activation (c-fos), and CORT levels in response to predator odor.
Main Methods:
- Manipulated CORT levels in postnatal day 8 (PN8) and PN12 rat pups using exogenous CORT administration and adrenalectomy with CORT replacement.
- Measured fear expression (immobility), amygdala activity (c-fos), and CORT levels in response to predator odor, littermate odor, and no odor.
Main Results:
- Exogenous CORT prematurely induced fear and basolateral/lateral amygdala activity in PN8 pups.
- Adrenalectomy in PN12 pups blocked fear expression and amygdala activation, which was reversed by CORT replacement.
- Low neonatal CORT levels appear to protect against fear responses and attenuate amygdala activation.
Conclusions:
- Neonatal corticosterone levels play a critical role in the developmental emergence of fear responses and amygdala activation.
- Environmental factors affecting the neonatal CORT system may impact the development of the fear system and its neural control.
Abstract:
In many altricial species, fear responses such as freezing do not emerge until sometime later in development. In infant rats, fear to natural predator odors emerges around postnatal day (PN) 10 when infant rats begin walking. The behavioral emergence of fear is correlated with two physiological events: functional emergence of the amygdala and increasing corticosterone (CORT) levels. Here, we hypothesize that increasing corticosterone levels influence amygdala activity to permit the emergence of fear expression. We assessed the relationship between fear expression (immobility similar to freezing), amygdala function (c-fos) and the level of corticosterone in pups in response to presentation of novel male odor (predator), littermate odor and no odor. CORT levels were increased in PN8 pups (no fear, normally low CORT) by exogenous CORT (3 mg/kg) and decreased in PN12 pups (express fear, CORT levels higher) through adrenalectomy and CORT replacement. Results showed that PN8 expression of fear to a predator odor and basolateral/lateral amygdala activity could be prematurely evoked with exogenous CORT, while adrenalectomy in PN12 pups prevented both fear expression and amygdala activation. These results suggest that low neonatal CORT level serves to protect pups from responding to fear inducing stimuli and attenuate amygdala activation. This suggests that alteration of the neonatal CORT system by environmental insults such as alcohol, stress and illegal drugs, may also alter the neonatal fear system and its underlying neural control.
