The role of the BDNF Val66Met polymorphism in synaptic plasticity and Recognition memory

Abstract

A single nucleotide polymorphism of the human BDNF gene (Val66Met) may account for much of the variation in human memory performance. BDNF may influence memory via, either a modulation of acute plasticity (i.e. LTP), or a chronic influence on developing memory systems. Not only this, but BDNF could interact with different memory types in different ways. BDNF is concentrated most heavily in the hippocampus, and therefore would be likely to have a greater effect on hippocampal dependent memory. Recognition memory involves the contribution of two distinct retrieval processes, Recollection and Familiarity. Prior research suggests that Familiarity does not depend on the hippocampus, but Recollection does. Recent evidence has shown Recollection and Familiarity are associated with distinct event-related potentials (ERP): Familiarity with an early-onset effect called the FN400; and Recollection with a later positivity called the late positive component (LPC). Recent evidence suggests the successful recognition of famous faces is dependent on the hippocampus, whilst recognising a non-famous face is not. Study 1 employed a recently developed human sensory LTP paradigm in the intact human brain, and found subjects carrying the Met allele (Val/Met and Met/Met) had significantly less LTP than Val/Val individuals. Met/Met individuals also performed significantly less well in a test of visual memory. Further, the degree of LTP was significantly correlated with the index of visual memory. Study 2 found no genotype differences in FN400 amplitude (evoked when correctly recognising a previously presented face) were found. However, Val/Val individuals generated a significantly more positive LPC when correctly identifying an old face after a period of consolidation of 24 hours. Study 3 found differences between famous and non- famous face recognition, as well as between Val homozygotes and Met carriers. Famous faces elicited significantly greater activation in the hippocampus than non-famous faces. There was greater hippocampal activation seen for Val/Val individuals. There were no clear differences in the recognition of non-famous faces. These results suggest an exclusive role of BDNF in hippocampal dependent memory, with the mechanism of this likely to be a person’s ability to display LTP.