Hippocampal Protein Degradation is Required for the Consolidation of Context Memories
Mentor 1
Dr. Helmstetter
Mentor 2
Patrick Cullen
Location
Union Wisconsin Room
Start Date
24-4-2015 2:30 PM
End Date
24-4-2015 3:45 PM
Description
When animals are put into a novel context they form a memory of that environment. Animals that have formed this context memory do not show the deficits in context fear conditioning that usually follow immediate shock administration. This phenomenon is known as the context pre-exposure facilitation effect (CPFE). This paradigm provides a convenient method for examining how the hippocampus acquires, consolidates, and retrieves contextual information in the absence aversive stimuli (i.e. footshock). Forming a representation of a context following context exposure requires de novo protein synthesis in both the dorsal hippocampus (dHPC) and ventral hippocampus (vHPC). However, it remains unclear whether hippocampal activity-dependent protein degradation, which has been shown to underlie the consolidation and retrieval of aversive context memories, is required for the formation of context memory following exposure to a novel context. Using in vitro proteasome assays, we investigated the activity of the 20S proteasome by measuring three types of proteolytic activity (chymotrypsin-, trypsin-, and peptidylglutamyl-like) and the proteasome regulatory subunit Rpt6 in synaptosomal fractions from the dHPC and vHPC. We found that exposure to the context resulted in different changes in proteasome activity at different time points between the dHPC and vHPC. We then verified the funtional role of protein degradation in the hippocampus by blocking proteolytic activity following exposure to a novel context. Animals received a 5 minute exposure to the context followed by an immediate infusion of the proteasome inhibitor clasto-lactacystin β-lactone (βLac) (32ng/μl), anisomycin (ANI) (125 μg/ μl), or vehicle into either the dHPC or vHPC. Twenty-four hours later, animals were returned to the context and administered 5 immediate footshocks. Fear conditioning was assessed 24 hours following training. Animals that received either ANI or βLac after context exposure showed impaired context conditioning compared to vehicle controls. These data suggest that both protein synthesis and protein degradation are required for the formation of a context representation in both the dorsal and ventral hippocampus. Taken together, the data from the current study suggest that protein degradation is required in the hippocampus to successfully consolidate a contextual memory and that the dHPC and vHPC undergo biochemically distinct degradation processes.
Hippocampal Protein Degradation is Required for the Consolidation of Context Memories
Union Wisconsin Room
When animals are put into a novel context they form a memory of that environment. Animals that have formed this context memory do not show the deficits in context fear conditioning that usually follow immediate shock administration. This phenomenon is known as the context pre-exposure facilitation effect (CPFE). This paradigm provides a convenient method for examining how the hippocampus acquires, consolidates, and retrieves contextual information in the absence aversive stimuli (i.e. footshock). Forming a representation of a context following context exposure requires de novo protein synthesis in both the dorsal hippocampus (dHPC) and ventral hippocampus (vHPC). However, it remains unclear whether hippocampal activity-dependent protein degradation, which has been shown to underlie the consolidation and retrieval of aversive context memories, is required for the formation of context memory following exposure to a novel context. Using in vitro proteasome assays, we investigated the activity of the 20S proteasome by measuring three types of proteolytic activity (chymotrypsin-, trypsin-, and peptidylglutamyl-like) and the proteasome regulatory subunit Rpt6 in synaptosomal fractions from the dHPC and vHPC. We found that exposure to the context resulted in different changes in proteasome activity at different time points between the dHPC and vHPC. We then verified the funtional role of protein degradation in the hippocampus by blocking proteolytic activity following exposure to a novel context. Animals received a 5 minute exposure to the context followed by an immediate infusion of the proteasome inhibitor clasto-lactacystin β-lactone (βLac) (32ng/μl), anisomycin (ANI) (125 μg/ μl), or vehicle into either the dHPC or vHPC. Twenty-four hours later, animals were returned to the context and administered 5 immediate footshocks. Fear conditioning was assessed 24 hours following training. Animals that received either ANI or βLac after context exposure showed impaired context conditioning compared to vehicle controls. These data suggest that both protein synthesis and protein degradation are required for the formation of a context representation in both the dorsal and ventral hippocampus. Taken together, the data from the current study suggest that protein degradation is required in the hippocampus to successfully consolidate a contextual memory and that the dHPC and vHPC undergo biochemically distinct degradation processes.
