A High-Resolution
            <i>In Vivo</i>
            Atlas of the Human Brain's Serotonin System

Beliveau, Vincent; Ganz, Melanie; Feng, Li; Ozenne, Brice; Højgaard, Liselotte; Fisher, Patrick M.; Svarer, Claus; Greve, Douglas N.; Knudsen, Gitte M.

doi:10.1523/jneurosci.2830-16.2017

Cited by 161 publications

(296 citation statements)

References 11 publications

Supporting

Mentioning

286

Contrasting

Order By: Relevance

“…The subject maps were aligned to the MNI152 template and averaged to produce a map of serotonin receptor densities at 1mm isotropic voxels. The atlas demonstrated high correlations with postmortem data as well as mRNA expression using the Allen Human Brain Atlas (27).…”

Section: Discussionmentioning

confidence: 96%

“…Mapping hippocampal serotonin receptor distributions. We used a previously published atlas of the serotonin receptor subtypes (5-HT1A, 5-HT1B 5-HT2A, 5-HT4) and the serotonin transporter (5-HTT) (27) derived from PET images of 210 healthy subjects to examine 1) Average density of each serotonin receptor within hippocampal subfields, and 2) Density of serotonin receptor subtypes mapped onto hippocampal surfaces, with the aim of correlating structural differences observed between HC and FEP with serotonin receptor densities.…”

Section: Discussionmentioning

confidence: 99%

“…First, we sought to replicate previous volumetric studies in FEP examining the hippocampal subfields and shape, while interrogating the entire hippocampal circuit including the white matter tracts. We then tested whether neuroanatomical anomalies would correlate with glutamate receptor densities, by leveraging an in-vivo atlas of the serotonin receptor system (27) combined with gene expression data from the Allen Human Brain Atlas(28) as a method of exploring mutative mechanistic explanations behind structural deficits in FEP. We searched for gene expression correlations between serotonin and glutamate receptor genes such that the distribution of a serotonin receptor subtype may predict glutamate receptor distribution.…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Ultra-high field imaging of hippocampal neuroanatomy in first episode psychosis demonstrates receptor-specific morphometric patterning

Park

Jeon

Khan

et al. 2019

Preprint

View full text Add to dashboard Cite

Objective. The hippocampus is considered a putative marker in schizophrenia with early volume deficits of select subfields. Certain subregions are thought to be more vulnerable due to a glutamate-driven mechanism of excitotoxicity, hypermetabolism, and then degeneration. Here, we explored whether hippocampal anomalies in first-episode psychosis (FEP) correlate with glutamate receptor density via a serotonin receptor proxy by leveraging structural neuroimaging, spectroscopy (MRS), and gene expression.Methods. High field 7T brain MR images were collected from 27 control, 41 FEP participants, along with 1H-MRS measures of glutamate. Automated methods were used to delineate the hippocampus and atlases of the serotonin receptor system were used to map receptor density across the hippocampus and subfields. We used gene expression data from the Allen Human Brain Atlas to test for correlations between serotonin and glutamate receptor genes.Results. We found reduced hippocampal volumes in FEP, replicating previous findings.Amongst the subfields, CA4-dentate gyrus showed greatest reductions. Gene expression analysis indicated 5-HTR1A and 5-HTR4 receptor subtypes as predictors of AMPA and NMDA receptor expression, respectively. Volumetric differences in the subfields correlated most strongly with 5-HT1A (R=0.64, p=4.09E-03) and 5-HT4 (R=0.54, p=0.02) densities as expected, and replicated using previously published data from two FEP studies. Measures of individual structure-receptor alignment were derived through normative modeling of hippocampal shape and correlations to receptor distributions, termed Receptor-Specific Morphometric Signatures (RSMS). Right-sided 5-HT4 RSMS was correlated with glutamate (R=0.357, p=0.048). Conclusions.We demonstrate glutamate-driven hippocampal remodeling in FEP through a receptor-density gated mechanism, thus providing a mechanistic explanation of how redox dysregulation affects brain structure and symptomatic heterogeneity in schizophrenia.

show abstract

Section: Discussionmentioning

confidence: 96%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Ultra-high field imaging of hippocampal neuroanatomy in first episode psychosis demonstrates receptor-specific morphometric patterning

Park

Jeon

Khan

et al. 2019

Preprint

View full text Add to dashboard Cite

show abstract

“…A viable way of making use of this concept whilst avoiding these assumptions is by integration of positron emission tomography (PET) or single photon computed emission tomography (SPECT) derived tissue property maps. Recent advancements in PET and SPECT tracer development resulted in a variety of novel tracers that can reliably measure the availability of specific receptors but also functional aspects such as synthesis capacity across a variety of neurotransmitters (Beliveau et al, 2016;Lehto et al, 2015;Mawlawi et al, 2001;McCann et al, 2005;Smith et al, 1998). Such PET-and SPECT-derived maps provide a more direct measurement of specific tissue properties as compared to mRNA expression.…”

Section: Introductionmentioning

confidence: 99%

JuSpace: A tool for spatial correlation analyses of magnetic resonance imaging data with nuclear imaging derived neurotransmitter maps

Dukart

Holiga

Rullmann

et al. 2020

Preprint

View full text Add to dashboard Cite

Recent studies have shown that drug-induced spatial alteration patterns in resting state functional activity as measured using magnetic resonance imaging (MRI) are associated with the distribution of specific receptor systems targeted by respective compounds. Based on this approach, we introduce a Matlab-based toolbox (JuSpace) allowing for cross-modal correlation of MRI-based measures with positron emission tomography (PET) and single photon emission computed tomography (SPECT) derived estimates covering various receptor systems including dopaminergic, serotonergic, noradrenergic, and GABAergic (gamma-aminobutric acid) neurotransmission. We apply JuSpace to two datasets covering Parkinson's disease patients (PD) on and off levodopa and risperidone-induced changes in rsfMRI and cerebral blood flow (CBF). We correlate rsfMRI derived PD-and levodopa-induced local activity alterations with PET and SPECT maps covering the above neurotransmitter systems.Similarly, we correlate the effects of risperidone on CBF with respective maps. Consistently with the predominant neurodegeneration of dopaminergic and serotonergic system in PD, we find significant spatial associations between rsfMRI activity alterations in PD on and off levodopa and dopaminergic (D2) and serotonergic systems (5-HT1b). Consistently with its mechanism of action, risperidone induced CBF alterations were correlated with key targets of serotonergic and dopaminergic systems. The JuSpace toolbox provides an easy framework for correlation of spatial alteration patterns across different neuroimaging modalities with PET derived receptor maps. Taken together, toolbox allows for cross-modal biologically meaningful evaluation and interpretation of image-derived spatial alteration patterns.

show abstract

“…Positron emission tomography (PET) shows that 5-HT 4 receptors (5-HT 4 R) are particularly abundant in brain regions involved in affective processing and memory, including the hippocampus, amygdala, and frontal cortex (Eglen, Wong, Dumuis, & Bockaert, 1995;Lucas, 2009). Our research group has recently published a high-resolution in vivo atlas of the serotonin system in humans, including the 5-HT 4 R (Beliveau & Ganz, 2017; downloadable maps are available at this website: https://nru.dk/FS5ht-atlas). Experimental studies also show that pharmacological stimulation of 5HT 4 R improves memory consolidation (Bockaert, Claeysen, Compan, & Dumuis, 2008;King, Marsden, & Fone, 2008), possibly through increased release of acetylcholine (Bockaert, Claeysen, Compan, & Dumuis, 2004).…”

mentioning

confidence: 99%

Brain serotonin 4 receptor binding is inversely associated with verbal memory recall

et al. 2017

Self Cite

View full text Add to dashboard Cite

BackgroundWe have previously identified an inverse relationship between cerebral serotonin 4 receptor (5‐HT 4R) binding and nonaffective episodic memory in healthy individuals. Here, we investigate in a novel sample if the association is related to affective components of memory, by examining the association between cerebral 5‐HT 4R binding and affective verbal memory recall.MethodsTwenty‐four healthy volunteers were scanned with the 5‐HT 4R radioligand [11C]SB207145 and positron emission tomography, and were tested with the Verbal Affective Memory Test‐24. The association between 5‐HT 4R binding and affective verbal memory was evaluated using a linear latent variable structural equation model.ResultsWe observed a significant inverse association across all regions between 5‐HT 4R binding and affective verbal memory performances for positive (p = 5.5 × 10−4) and neutral (p = .004) word recall, and an inverse but nonsignificant association for negative (p = .07) word recall. Differences in the associations with 5‐HT 4R binding between word categories (i.e., positive, negative, and neutral) did not reach statistical significance.ConclusionOur findings replicate our previous observation of a negative association between 5‐HT 4R binding and memory performance in an independent cohort and provide novel evidence linking 5‐HT 4R binding, as a biomarker for synaptic 5‐HT levels, to the mnestic processing of positive and neutral word stimuli in healthy humans.

show abstract

A High-Resolution In Vivo Atlas of the Human Brain's Serotonin System

Cited by 161 publications

References 11 publications

Ultra-high field imaging of hippocampal neuroanatomy in first episode psychosis demonstrates receptor-specific morphometric patterning

Ultra-high field imaging of hippocampal neuroanatomy in first episode psychosis demonstrates receptor-specific morphometric patterning

JuSpace: A tool for spatial correlation analyses of magnetic resonance imaging data with nuclear imaging derived neurotransmitter maps

Brain serotonin 4 receptor binding is inversely associated with verbal memory recall

Contact Info

Product

Resources

About