A role for calcium-calmodulin-dependent protein kinase II in the consolidation of visual object recognition memory.

The aim was to investigate the role of calcium-calmodulin-dependent protein kinase (CAMK)II in object recognition memory. The performance of rats in a preferential object recognition test was examined after local infusion of the CAMKII inhibitors KN-62 or autocamtide-2-related inhibitory peptide (AIP) into the perirhinal cortex. KN-62 or AIP infused after acquisition impaired memory tested at 24 h, indicating an involvement of CAMKII in the consolidation of recognition memory. Memory was impaired when KN-62 was infused at 20 min after acquisition or when AIP was infused at 20, 40, 60 or 100 min after acquisition. The time-course of CAMKII activation in rats was further examined by immunohistochemical staining for phospho-CAMKII(Thre286)alpha at 10, 40, 70 and 100 min following the viewing of novel and familiar images. At 70 min, processing novel images resulted in more phospho-CAMKII(Thre286)alpha-stained neurons in the perirhinal cortex than did the processing of familiar images, consistent with the viewing of novel images increasing the activity of CAMKII at this time. This difference was eliminated by prior infusion of AIP. These findings establish that CAMKII is active within the perirhinal region between approximately 20 and 100 min following learning and then returns to baseline. Thus, increased CAMKII activity is essential for the consolidation of long-term object recognition memory but continuation of that increased activity throughout the 24 h memory delay is not necessary for maintenance of the memory.

Stereological analysis of regional brain volumes and neuron numbers in rats displaying a spontaneous hydrocephalic condition.

Stereological methods were employed to investigate a novel spontaneously occurring brain mutation in an inbred colony of Wistar rats. These mutants displayed changes (enlarged cerebral ventricles and malformed hippocampi) similar to those seen in H-Tx hydrocephalic rats. Mutant and control rats were studied at three postnatal ages: 4, 7, and 13 weeks. Brain weight in the mutant animals was significantly (P < 0.05) increased when compared to age-matched controls. Using systematic random sampling and the Cavalieri principle we estimated the volumes of various brain compartments, including the cerebral ventricles, forebrain, and cerebral cortex. We found that ventricular volume (P < 0.001) and forebrain volume (P < 0.05) were significantly increased in mutant rats when compared to control rats. Total numbers of nucleoli, estimated using the physical fractionator, were obtained for neurons in the cerebral cortex and granule cells in the dentate gyrus. Numbers were not altered significantly in mutant rats. Nor were mean soma volumes as estimated from total volumes and numbers. The changes in brain and ventricle volumes provide quantitative evidence that these animals display a hydrocephalic condition. This condition appears not to compromise cell number or mean soma size in the brain regions examined.