Influence of brain-derived neurotrophic factor val66met human polymorphism on declarative memory consolidation

The Brain-Derived Neurotrophic Factor (BDNF) is a neurotrophin which in the adult brain regulates long-term potentiation. In humans, valine (val) to methionine (met) substitution in the 5’ pro-region of the BDNF protein is associated with poorer episodic memory. Neurons transfected with met-BDNF-Green Fluorescence Protein showed lower depolarization-induced secretion, while constitutive secretion is unchanged. Here, we hypothesized that the differences in BDNF release determined by this polymorphism would influence memory consolidation and that in comparison with the val/met (=val/met or met/met), val/val individuals would show higher memory performance and different brain responses during a 16h-delayed rather than immediate retrieval session. Participants encoded a series of neutral faces in the afternoon. Retrieval sessions took place one hour after the encoding session, and in the following morning, during the acquisition of functional Magnetic Resonance Imaging (fMRI) time series with a 3 Tesla Allegra scanner. During retrieval, studied faces and new ones were presented in random order. For each stimulus, the subjects indicated whether they could retrieve the encoding episode with (“Remember”), or without details (“Know”), or if they thought the item had not been presented during encoding (“New”). A repeated-measure ANOVA on discrimination index (d’) showed significant effects of group (F(1, 27)=8.65, p=0.007, n(val/val)=14, n(val/met)=15) and session (F(1, 27)=24.64, p=0.000), although the group by session interaction was not significant (F(1, 27)=1.29, p=0.267). fMRI results showed a significant genotype (val/val > val/met) by session (delayed > immediate retrieval) by memory type (Remember > Know) interaction in the right inferior occipital gyrus (x=42, y=-78, z=0, p=0.004, Z=3.77), the left inferior parietal lobule (x=-56, y=-40, z=48, p=0.013, Z=3.43), the posterior cingulate cortex (x=14, y=-42, z=42, p=0.019, Z=3.29) and the right hippocampus (x=28, y=-22, z=-22, p=0.03, Z=3.11). Val/val individuals demonstrate higher memory performance than met-carriers but the change in memory performance between immediate and delayed retests is similar in both allelic groups. In contrast, neural correlates of recollection change between sessions differently according to genotype: responses increase significantly more in val/val than in val/met individuals in brain areas involved in the retrieval, accumulation and binding of perceptual memory details during delayed, relative to immediate retest. These data suggest that activity-dependent BDNF release promotes memory consolidation during the first post-training hours