Single 5HTR2A-1438 A/G nucleotide polymorphism affects performance in a metacontrast masking task: implications for vulnerability testing and neuromodulation of pyramidal cells

Abstract

It is known that 5HTR2A (rs6311) receptors have high concentration in the cortical layer-5 pyramidal neurons and that these receptors play an important role in the modulation of neurocognitive functions. For example, layer-5 pyramidal neurons mediate cellular level integrative interaction of primary sensory afferent signals and top-down signals exerting contextual modulatory influence. It is also known that genetic variability of 5HTR2A is implicated in individual differences in mental processes. Interestingly, serotonin selectively enhances the asynchronous type of glutamate release when modulating the activity of cortical layer-5 pyramidal neurons, with a post-stimulation delay of this effect at about 50 ms. There are not many behavioral tasks capable of tapping that small temporal intervals in terms of change of the values of independent variables leading to an observable change in the subjects' behavior. However, in the metacontrast masking vision task stimulus onset asynchronies between target and mask critical for the change in the expression of the masking effect correspond to this small temporal value. Thus we hypothesized that genetic variability in 5HTR2A (rs6311) is likely to be associated with different behavioral effects of metacontrast masking and more specifically, that because A allele carriers typically demonstrate greater promoter activity, target-to-mask asynchrony variations should have stronger impact on the masking effect especially with this group of subjects. We obtained support for this hypothesis, but only when target and mask shapes were mutually incongruent.

Keywords: 5HTR2A (rs6311); Endophenotype; Individual differences; Layer-5 pyramidal neuron; Metacontrast masking; Serotonin.