The 5‐HT₄ receptor levels in hippocampus correlates inversely with memory test performance in humans

Abstract

The cerebral serotonin (5-HT) system is involved in cognitive functions such as memory and learning and animal studies have repeatedly shown that stimulation of the 5-HT type 4 receptor (5-HT4 R) facilitates memory and learning and further that the 5-HT4 R modulates cellular memory processes in hippocampus. However, any associations between memory functions and the expression of the 5-HT4 R in the human hippocampus have not been investigated. Using positron emission tomography with the tracer [(11) C]SB207145 and Reys Auditory Verbal Learning Test we aimed to examine the individual variation of the 5-HT4R binding in hippocampus in relation to memory acquisition and consolidation in healthy young volunteers. We found significant, negative associations between the immediate recall scores and left and right hippocampal BPND , (p = 0.009 and p = 0.010 respectively) and between the right hippocampal BPND and delayed recall (p = 0.014). These findings provide evidence that the 5-HT4 R is associated with memory functions in the human hippocampus and potentially pharmacological stimulation of the receptor may improve episodic memory.

The Center for Integrated Molecular Brain Imaging (Cimbi) database

“…These data have so far mostly been used in conjunction with imaging data, e.g., da Cunha-Bang et al (2013, and Haahr et al (2013) but have also served as a basis for analyses in their own right (Stenbaek et al, 2014a(Stenbaek et al, , 2014b.…”

“…We have been particularly interested in how individual differences in healthy volunteers may serve as important predictors of vulnerability to neuropsychiatric disorders, including personality traits (da Cunha-Bang et al, 2013;Frokjaer et al, 2008;Kalbitzer et al, 2009), affective disorders Frokjaer et al, 2009Macoveanu et al, 2014;Madsen et al, 2014) and memory disorders (Haahr et al, 2013;Madsen et al, 2011c;Madsen et al, 2011a). We have primarily chosen to investigate healthy volunteers in order to exclude confounds such as medication bias and scar effects from prior disease processes and to separate trait and state factors.…”

Cortical surface-based analysis reduces bias and variance in kinetic modeling of brain PET data

“…These data sets have been used in two other studies. However, one was a ROI-based analysis (Fisher et al, 2012) and the second focused on specific binding only within hippocampus (Haahr et al, 2012a). The protocol was approved by the Ethics Committee of Copenhagen and Frederiksberg, Denmark, and all subjects gave written informed consent.…”

Neurotransmitters and Memory

“…Notably, aging, AD, and amnesia are associated to decrements in 5-HT markers such as SERT and in the number of 5-HT 1A-1B, 5-HT 2A/2C , 5-HT 4 , 5-HT 6 , and 5-HT 7 receptors (for references see Rodríguez et al, 2012;Xu et al, 2012). Also emerging evidence indicates that memory formation, amnesia, promnesic and amnesic drugs modify serotonergic markers, including 5-HT receptors, SERT, and serotonergic tone (Belcher et al, 2005;Callaghan et al, 2012;Da Silva Costa-Aze et al, 2012;Eriksson et al, 2012;Fournet et al, 2012;Frankland et al, 2013;Froestl et al, 2012Froestl et al, , 2013Garcia-Alloza et al, 2004;Goldenhuys and Van der Schyf, 2009;Gong et al, 2012;Haahr et al, 2012;Hermann et al, 2012;Huerta-Rivas et al, 2010;Jones and Moller, 2011;Lorke et al, 2006;Liy-Salmeron, 2008;Marin et al, 2012a;Marin et al, 2012b;Marcos et al, 2006Marcos et al, , 2008Marshall and O'Dell, 2012;Mathur and Lovinger, 2012;Meneses et al, , 2011aNa et al, 2012;Pérez-García et al, 2006;Pérez-García and Meneses, 2008a;Pérez-García and Meneses, 2009;Tellez et al, 2010Tellez et al, , 2012. Certainly, in this context, 5-HT systems, protocols of training/testing, memory tasks and drugs (see e.g., Meneses, 2013) deserve attention.…”