Functional Interaction between the Amygdala and Entorhinal Cortex in Modulating Cocaine Associated Learning and Memory

Abstract

ABSTRACT Emotional arousal events tend to be remembered vividly than neutral ones Neuroanatomical studies have suggested that amygdala is involved in memory consolidation by facilitating or dampening emotional arousal level It is well known that the amygdala modulates positively and negative emotional memory including drug-cues associated memory and fear memory The present study aims to elucidate the role of amygdala in the consolidation reconsolidation of cocaine associated memory and in the formation of cued-fear memory In part 1 we used cocaine-induced conditioned place preference to examine the role of functional interaction between the basolateral nucleus of amygdala (BLA) and entorhinal cortex (EC) in cocaine-conditioned memory First to elucidate whether BLA and EC are involved in the consolidation of cocaine-conditioned memory we transiently inactivated BLA or EC with muscimol a GABAA agonist immediately after training To further understand whether BLA and EC are critical for the retrieval of cocaine conditioned place preference intra-BLA or -EC muscimol infusion prior to the CPP test decreased cocaine-induced CPP Furthermore Inactivation of BLA or EC immediately after the CPP test decreased subsequent performance in cocaine-induced CPP These results taken together suggest that BLA and EC are necessary for cocaine-induced CPP performance Based on our findings we hypothesized that BLA in together with EC may modulate the reconsolidation of cocaine-induced CPP To test the hypothesis BLA and EC were functionally disconnected from each other by using unilateral muscimol infusion method Importantly ipsilateral intra-BLA and -EC muscimol infusion immediately after the CPP retrieval did not affect subsequent cocaine induced CPP However contralateral intra-BLA and -EC muscimol infusion immediately after the CPP retrieval drastically decreased subsequent cocaine-induced CPP Finally to examine whether is there a BLA- or EC- independent neural circuit for the formation of cocaine-induced CPP After the retrieval of cocaine conditioned memory the animals with BLA or EC lesion by ibotenic acid underwent new cocaine conditionings expressed the new cocaine-induced CPP According to the finding we supposed that there are complementary brain regions for the formation of new cocaine-induced CPP For testing the hypothesis the Fos immunostaining technique was used The results revealed that the rats receiving new cocaine conditioning following BLA EC or BLA and EC lesion exhibited higher numbers of Fos-positive nuclei in the prefrontal cortex and less numbers of Fos-positive nuclei in the central nuclei of amygdala than sham control group We hereby conclude that BLA and EC are necessary for the storage of cocaine-induced CPP Ipsilateral reciprocal neural activity between BLA and EC is involved in modulating the reconsolidation of cocaine-induced CPP The PFC and are essential for the formation of new cocaine-induced CPP after BLA and EC lesion In part 2 we want to understand whether there are sex differences in the activation of the amygdala during cue-induced fear conditionings processing After cued fear conditioning procedure female mice exhibited a more robust cued fear memory than male mice Systemic testosterone administrations and an intra-LA testosterone infusion eliminated the CS-induced freezing in gonadectomized male mice while testosterone administrations did not affect the CS-induced freezing in intact or OVX female mice Hence these findings suggest that there is sex difference in the effect of testosterone on cued fear conditioning

Date of Award	2014 Jun 27
Original language	English
Supervisor	Lung Yu (Supervisor)