Human Sensory LTP Predicts Memory Performance and Is Modulated by the BDNF Val66Met Polymorphism.

Meg J Spriggs,Nicole S Mckay,Nicolas A Mcnair,Chris S Thompson,Karen E Waldie,Timothy J Teyler,Jeff P Hamm,Ushtana Antia,Andrew N Shelling,Yvette N Lamb,Rohan O C King,Bruce R Russell,Ian J Kirk,David Moreau,C Carolyn Wu

doi:10.3389/fnhum.2019.00022

Abstract

Background: Long-term potentiation (LTP) is recognised as a core neuronal process underlying long-term memory. However, a direct relationship between LTP and human memory performance is yet to be demonstrated. The first aim of the current study was thus to assess the relationship between LTP and human long-term memory performance. With this also comes an opportunity to explore factors thought to mediate the relationship between LTP and long-term memory. The second aim of the current study was to explore the relationship between LTP and memory in groups differing with respect to brain-derived neurotrophic factor (BDNF) Val66Met; a single-nucleotide polymorphism (SNP) implicated in memory function.Methods: Participants were split into three genotype groups (Val/Val, Val/Met, Met/Met) and were presented with both an EEG paradigm for inducing LTP-like enhancements of the visually-evoked response, and a test of visual memory.Results: The magnitude of LTP 40 min after induction was predictive of long-term memory performance. Additionally, the BDNF Met allele was associated with both reduced LTP and reduced memory performance.Conclusions: The current study not only presents the first evidence for a relationship between sensory LTP and human memory performance, but also demonstrates how targeting this relationship can provide insight into factors implicated in variation in human memory performance. It is anticipated that this will be of utility to future clinical studies of disrupted memory function.

Highlights

First demonstrated in vivo in 1973 (Bliss and Lømo, 1973), long-term potentiation (LTP) has since been widely recognised as the principal model for the neuronal basis of long-term memory
The primary aim of the current study was to assess this relationship using the visual LTP paradigm and two subtests of the Wechsler Memory Scale-III (WMS-III; Wechsler et al, 2007) that are widely used in clinical assessments of delayed visual recognition memory (Conklin et al, 2002; Keilp et al, 2006; Seelye et al, 2009; Vann et al, 2009)
The current study provides the first evidence that the degree of visually-induced LTP is a significant predictor of human visual memory performance

Summary

Introduction

First demonstrated in vivo in 1973 (Bliss and Lømo, 1973), long-term potentiation (LTP) has since been widely recognised as the principal model for the neuronal basis of long-term memory. The cellular and molecular mechanisms of LTP have been studied extensively in vivo and in vitro in laboratory animals, which typically involves the application of direct neuronal electrical stimulation and results in an enhancement of the response in a neighbouring cell (Bliss and Lømo, 1973; Harris et al, 1984; Teyler and DiScenna, 1987; Kirkwood and Bear, 1994; Figurov et al, 1996) Such studies have demonstrated that, in its most widespread form, LTP is dependent on the influx of Ca2+ through N-methyl-D-aspartate (NMDA) receptors, leading to long-term alterations in cell structure and function, and an increase in synaptic efficacy. The second aim of the current study was to explore the relationship between LTP and memory in groups differing with respect to brain-derived neurotrophic factor (BDNF) Val66Met; a single-nucleotide polymorphism (SNP) implicated in memory function

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Discussion

Conclusion