Impaired conditioned taste aversion learning in spinophilin knockout mice

Plasticity in dendritic spines may underlie learning and memory. Spinophili n, a protein enriched in dendritic spines, has the properties of a scaffold ing protein and is believed to regulate actin cytoskeletal dynamics affecti ng dendritic spine morphology. It also binds protein phosphatase-1 (PP-1), an enzyme that regulates dendritic spine physiology. In this study, we test ed the role of spinophilin in conditioned taste aversion learning (CTA) usi ng transgenic spinophilin knockout mice. CTA is a form of associative learn ing in which an animal rejects a food that has been paired previously with a toxic effect (e.g., a sucrose solution paired with a malaise-inducing inj ection of lithium chloride). Acquisition and extinction of CTA was tested i n spinophilin knockout and wild-type mice using taste solutions (sucrose or sodium chloride) or flavors (Kool-Aid) paired with moderate or high doses of LiCl (0-15 M, 20 or 40 mL/kg). When sucrose or NaCl solutions were paire d with a moderate dose of LiCl, spinophilin knockout mice were unable to le arn a CTA. At the higher dose, knockout mice acquired a CTA but extinguishe d more rapidly than wild-type mice. A more salient flavor stimulus (taste p lus odor) revealed similar CTA learning at both doses of LiCl in both knock outs and wild types. Sensory processing in the knockouts appeared normal be cause knockout mice and wild-type mice expressed identical unconditioned ta ste preferences in two-bottle tests, and identical lying-on-belly responses to acute LiCl. We conclude that spinophilin is a candidate molecule requir ed for normal CTA learning.