The effect of neurogranin on neural correlates of episodic memory encoding and retrieval

Abstract

Neurogranin (NRGN) is the main postsynaptic protein regulating the availability of calmodulin-Ca(2+) in neurons. NRGN is expressed exclusively in the brain, particularly in dendritic spines and has been implicated in spatial learning and hippocampal plasticity. Genetic variation in rs12807809 in the NRGN gene has recently been confirmed to be associated with schizophrenia in a meta-analysis of genome-wide association studies: the T-allele was found to be genome-wide significantly associated with schizophrenia. Cognitive tests and personality questionnaires were administered in a large sample of healthy subjects. Brain activation was measured with functional magnetic resonance imaging (fMRI) during an episodic memory encoding and retrieval task in a subsample. All subjects were genotyped for NRGN rs12807809. There was no effect of genotype on personality or cognitive measures in the large sample. Homozygote carriers of the T-allele showed better performance in the retrieval task during fMRI. After controlling for memory performance, differential brain activation was evident in the anterior cingulate cortex for the encoding and posterior cingulate regions during retrieval. We could demonstrate that rs12807809 of NRGN is associated with differential neural functioning in the anterior and posterior cingulate. These areas are involved in episodic memory processes and have been implicated in the pathophysiology of schizophrenia in structural and functional imaging as well as postmortem studies.

Fig. 1.

Cortical activation during face encoding: top row (brain images) illustrates activations mapped on the standard SPM brain template. Lower left side depicts higher activation of T/T allele carriers compared with T/C and C/C allele carriers in the anterior cingulate (LCing) and the lingual gyrus (LingG) (results: P < .001; Monte Carlo simulated, error bars represent standard error of the mean). Colored bar (bottom right) represents t values. The images are oriented in neurological convention (right hemisphere of the brain corresponds to the right side of the image).

Fig. 2.

Cortical activation during face retrieval: top row (brain images) illustrates activations (left precentral gyrus not shown) mapped on the standard SPM brain template. Lower left side depicts parameter estimates derived from clusters of higher activation (due to less deactivation) in T/T allele carriers as compared with T/C and C/C allele carriers in left insula (Insula), left precentral gyrus (PreC), and the cingulate cortex (r_Cingulate; expanding to the right precentral gyrus) (results: P < .001; Monte Carlo simulated, error bars represent standard error of the mean). Colored bar (bottom right) represents t values. The images are oriented in neurological convention (right hemisphere of the brain corresponds to the right side of the image).