Impaired striatum-dependent behavior in GASP-1-knock-out mice

Area of Science:

• Neuroscience
• Molecular Biology
• Behavioral Science

Background:

• G protein-coupled receptor (GPCR) associated sorting protein-1 (GASP-1) is implicated in GPCR recycling and degradation.
• GASP-1 knockout (GASP-1-KO) mice exhibit deficits in cocaine self-administration and altered striatal receptor regulation.

Purpose of the Study:

• To investigate the cognitive functions of GASP-1-KO mice across various memory tasks.
• To determine if GASP-1 deficiency impacts memory processes underlying operant conditioning and complex behavior acquisition.

Main Methods:

• Behavioral testing of GASP-1-KO mice and wild-type (WT) littermates in a range of memory paradigms.
• Assessment of procedural memory (food-reinforced bar-press task) and spatial learning (water maze).
• Evaluation of simple behavioral responses using Barnes maze, object recognition, and passive avoidance tasks.

Main Results:

• GASP-1-KO mice demonstrated delayed acquisition in a food-reinforced bar-press task, indicating procedural memory deficits.
• While water maze acquisition was similar, GASP-1-KO mice showed increased thigmotaxis and reduced swim efficiency.
• No deficits were observed in tasks requiring simple responses, suggesting affected complex response acquisition/expression.

Conclusions:

• GASP-1 deficiency impairs procedural memory and the acquisition/expression of complex behaviors.
• Hippocampal function remains intact, with preserved spatial memory retention.
• The behavioral phenotype of GASP-1-KO mice supports a role for striatal GPCRs in skilled behavior and motivation, making them a valuable research tool.