Hippocampal 5-HT4 serotonin receptor levels predict memory performance in human volunteers

The neurochemical basis of cognitive functions is one of the most fundamental of cognitive neuroscience research areas. Indeed, there is a vast body of literature documenting the effects of manipulating function of various neurotransmitter systems on different cognitive and perceptual functions. Given the increasing incidence of memory deficits with aging populations in western countries, neurotransmitter basis of memory functions is one of the most prominent research questions in this exciting area of research. In addition to findings linking acetylcholine function with memory consolidation, there is a body of literature suggesting a significant role for serotonin system in memory functions.

A recent study by Dr. Mette Haahr et al. (2012) combined mapping of levels of specific serotonin receptor called 5-HT4R in hippocampi of 30 healthy volunteers with neuropsychological measures of memory performance. Two memory tests were utilized; in a so-called Reys Auditory Verbal Learning Test, the participants were presented with 15 words on five separate accounts with free immediate recall of the list, as well as presentation of an interference list, on each trial. Delayed recall of the list occurred 30 minutes after the cessation of the task. This allowed deriving indices of both immediate recall and delayed recall. In another test called Rey-Osterrieth’s Complex Figure Test, the participants were to copy a complex geometric figure and then reproduce it from memory after delays of 3 and 30 minutes, with the number of aspects of the figure memorized after the 3-minute delay representing immediate recall, and memorization after the 30-min delay representing delayed recall.

When the memory performance of the participants was correlated with 5-HT4R receptor density in hippocampal areas, as quantified with positron emission tomography following injection of [11C]SB207145 tracer substance, negative correlations were observed between immediate recall scores in Reys Auditory Verbal Learning Test and 5-HT4R receptor densities in the hippocampus bilaterally, and with delayed recall scores in the right hippocampus. The authors note that theirs is the first study examining associations between hippocampal 5-HT4R density and memory functions in humans and, while the observed inverse relationship between receptor densities and memory function warrant further studies looking at the complex interactions between intrinsic serotonergic tonus and receptor levels, the authors suggest their findings predicting that stimulation of the human 5-HT4R could improve memory functions.

Reference: Haahr ME, Fisher P, Holst K, Madsen K, Jensen CG, Marner L, Lehel S, Baare W, Knudsen G, Hasselbalch S. The 5-HT4 receptor levels in hippocampus correlates inversely with memory test performance in humans. Human Brain Mapping (2012) e-publication ahead of print. http://dx.doi.org/ 10.1002/hbm.22123