Dataset Information

Role of densin-180 in mouse ventral hippocampal neurons in 24-hr retention of contextual fear conditioning.

ABSTRACT:

Introduction

Densin-180 interacts with postsynaptic molecules including calcium/calmodulin-dependent protein kinase II? (CaMKII?) but its function in learning and memory process has been unclear.

Methods

To investigate a role of hippocampal densin-180 in contextual fear conditioning (CFC) learning and memory processes, knockdown (KD) of densin-180 in hippocampal subareas was applied.

Results

First, ventral hippocampal (vHC) densin-180 KD impaired single-trial CFC (stCFC) memory one day later. stCFC caused freezing behaviors to reach the peak about one hour later in both control and KD mice, but then freezing was disappeared at 2 hr postshock in KD mice. Second, stCFC caused an immediate and transient reduction of vHC densin-180 in control mice, which was not observed in KD mice. Third, stCFC caused phosphorylated-T286 (p-T286) CaMKII? to change similarly to densin-180, but p-T305 CaMKII? was increased 1 hr later in control mice. In KD mice, these effects were gone. Moreover, both basal levels of p-T286 and p-T305 CaMKII? were reduced without change in total CaMKII? in KD mice. Fourth, we found double-trial CFC (dtCFC) memory acquisition and retrieval kinetics were different from those of stCFC in vHC KD mice. In addition, densin-180 in dorsal hippocampal area appeared to play its unique role during the very early retrieval period of both CFC memories.

Conclusion

This study shows that vHC densin-180 is necessary for stCFC memory formation and retrieval and suggests that both densin-180 and p-T305 CaMKII? at 1 ~ 2 hr postshock are important for stCFC memory formation. We conclude that roles of hippocampal neuronal densin-180 in CFC are temporally dynamic and differential depending on the pattern of conditioning stimuli and its location along the dorsoventral axis of hippocampal formation.

SUBMITTER: Kim CH

PROVIDER: S-EPMC7749528 | biostudies-literature | 2020 Dec

REPOSITORIES: biostudies-literature

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Publications

Role of densin-180 in mouse ventral hippocampal neurons in 24-hr retention of contextual fear conditioning.

Kim Chong-Hyun CH Kim Seoyul S Kim Su-Hyun SH Roh Jongtae J Jin Harin H Song Bokyung B

Brain and behavior 20201016 12

<h4>Introduction</h4>Densin-180 interacts with postsynaptic molecules including calcium/calmodulin-dependent protein kinase IIα (CaMKIIα) but its function in learning and memory process has been unclear.<h4>Methods</h4>To investigate a role of hippocampal densin-180 in contextual fear conditioning (CFC) learning and memory processes, knockdown (KD) of densin-180 in hippocampal subareas was applied.<h4>Results</h4>First, ventral hippocampal (vHC) densin-180 KD impaired single-trial CFC (stCFC) me ...[more]

PMID: 33064361

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Project description:Numerous studies have attributed the psychopathology of anxiety and stress disorders to maladaptive behavioral responses such as an inability to extinguish fear. Therefore, understanding neural substrates of fear extinction is imperative for developing more effective therapies for anxiety and stress disorders. Although several studies indicated a role for cholinergic transmission and nicotinic acetylcholine receptors (nAChRs) in anxiety and stress disorder symptomatology, very little is known about the specific contribution of nAChRs in the fear extinction process. In the present study, we first examined the involvement of several brain regions essential for fear extinction (i.e., dorsal and ventral hippocampus, dHPC and vHPC; infralimbic, IL, and prelimbic, PL of the medial prefrontal cortex, mPFC; basolateral nucleus of the amygdala, BLA) in the impairing effects of a nAChR agonist, nicotine, on contextual fear extinction in mice. Our results showed that systemic administration of nicotine during contextual fear extinction increased c-fos expression in the vHPC and BLA while not affecting dHPC, IL or PL. In line with these results, local nicotine infusions into the vHPC, but not dHPC, resulted in impaired contextual fear extinction. Interestingly, we found that local nicotine infusions into the PL also resulted in impairment of contextual fear extinction. Second, we measured the protein levels of the GABA synthesizing enzymes GAD65 and GAD67 in the dHPC and vHPC during contextual fear extinction. Our results showed that in the group that received acute nicotine, both GAD65 and GAD67 protein levels were downregulated in the vHPC, but not in dHPC. This effect was negatively correlated with the level of freezing response during fear extinction suggesting that the downregulated GAD65/67 levels were associated with disrupted fear extinction. Finally, using c-fos/GAD65/67 double immunofluorescence, we showed that nicotine mainly increased c-fos expression in non-GABAergic ventral hippocampal cells, indicating that acute nicotine increases vHPC excitability. Overall, our results suggest that acute nicotine's impairing effects on fear extinction are associated with ventral hippocampal disinhibition. Therefore, these results further our understanding of the interaction between nicotine addiction and anxiety and stress disorders by describing novel neural mechanisms mediating fear extinction.

Dataset Information

Role of densin-180 in mouse ventral hippocampal neurons in 24-hr retention of contextual fear conditioning.

Introduction

Methods

Results

Conclusion

Publications

Role of densin-180 in mouse ventral hippocampal neurons in 24-hr retention of contextual fear conditioning.

Similar Datasets

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