alpha CaMKII autophosphorylation controls exploratory activity to threatening novel stimuli

作者：Easton Alanna C; Lucchesi Walter; Schumann Gunter; Giese K Peter; Mueller Christian P; Fernandes Cathy^*

来源：Neuropharmacology, 2011, 61(8): 1424-1431.

DOI：10.1016/j.neuropharm.2011.08.036

• AlphaCaMKII
• Autophosphorylation
• Anxiety
• Hyperlocomotion
• Threat
• Novelty

Autophosphorylation of alpha CaMKII is regarded as a 'molecular memory' for Ca(2+) transients and a crucial mechanism in aversely, but less so in appetitively, motivated learning and memory. While there is a growing body of research implicating alpha CaMKII in general in behavioral responses to threat or fearful stimuli, little is known about the contribution of the autophosphorylation. The present study asked how alpha CaMKII autophosphorylation controls anxiety-like behavioral responses toward novel, potentially threatening stimuli. We tested homozygous and heterozygous T286A alpha CaMKII autophosphorylation deficient mice and wild types in a systematic series of behavioral tests. Homozygous mutants were more active in the open field test and showed reduced anxiety-related behavior in the light/dark test, but these findings were confounded by a hyperlocomotor phenotype. The analysis of elevated plus maze showed significantly reduced anxiety-related behavior in the alpha CaMKII autophosphorylation-deficient mice which appeared to mediate a hyperlocomotor response. An analysis of home cage behavior, where neither novel nor threatening stimuli were present, showed no differences in locomotor activity between genotypes. Increased locomotion was not observed in the novel object exploration test in the alpha CaMKII autophosphorylation-deficient mice, implying that hyperactivity does not occur in response to discrete novel stimuli. The present data suggest that the behavior of alpha CaMKII autophosphorylation-deficient mice cannot simply be described as a low anxiety phenotype. Instead it is suggested that alpha CaMKII autophosphorylation influences locomotor reactivity to novel environments that are potentially, but not necessarily threatening.

• 出版日期2011-12