Decoding the Laminar Chemoarchitectonic Contribution to Brain Function in the Macaque
Presented During: Poster Session 3
Friday, June 27, 2025: 01:45 PM - 03:45 PM
Friday, June 27, 2025: 01:45 PM - 03:45 PM
Presented During: Poster Session 4
Saturday, June 28, 2025: 01:45 PM - 03:45 PM
Saturday, June 28, 2025: 01:45 PM - 03:45 PM
Presented During:
Friday, June 27, 2025: 11:30 AM - 12:45 PM
Brisbane Convention & Exhibition Centre
Room:
M1 & M2 (Mezzanine Level)
Poster No:
1729
Submission Type:
Abstract Submission
Authors:
Thomas Funck1, Ting Xu2, Meiqi Niu3, Lucija Rappan4, Michael Milham2, Nicola Palomero-Gallagher5
Institutions:
1Child Mind Institute, Montréal, QC, 2Child Mind Institute, New York, NY, 3Research Centre Jülich, Jülich, North Rhine-Westphalia, 4Jülich Forschungszentrum, Jülich, North Rhine-Westphalia, 5Research Centre Jülich, Jülich, Jülich
First Author:
Co-Author(s):
Introduction:
The cortical and laminar distribution of neurotransmitter receptors is vital for brain function, yet the mechanisms for this remain poorly understood. High-resolution imaging of receptors is feasible only through ex vivo techniques like 2D autoradiography. We developed a 3D reconstruction algorithm, BrainBuilder[1], and used it to create 12 neurotransmitter receptor atlases for the macaque brain at 0.25mm³ resolution. Laminar receptor distributions from these atlases were compared with fMRI activation maps[2] and functional networks[3] to elucidate the role of neurotransmitters in brain function.
Methods:
Data Acquisition: Brains from 3 adult male Macaca fascicularis were removed, shock frozen (−40C), and serially sectioned to yield 20 μm thick sections. Alternating sections were processed to visualize 12 neurotransmitter receptor binding sites with quantitative in vitro receptor autoradiography[4,5].
Preprocessing: BrainBuilder was used to reconstruct 0.25 mm³ volumes for GABAA/B, AMPA, NMDA, Kainate, 5-HT1A, 5-HT2, M1, M2, M3, α1, and α2 receptors. Receptor densities were projected onto 18 cortical surfaces spanning the depth of the cortex, stratified into thirds (superficial, middle, and deep bins) and averaged. We applied surface smoothing (1mm FWHM) and averaged receptor densities across the 3 hemispheres to create 12 receptor maps x 3 depths through the cortex. Whole-depth receptor maps were also generated. Surfaces were transformed into Yerkes19 space[6,7] using MSM[8] and then to HCP human space via functional cross-species mapping[9].
Functional Mapping: 9 fMRI-derived functional maps were generated using neuroquery with the following keywords: association cortex, attention, auditory, emotion, executive, memory, motor, somatosensory, and visual. These maps were projected onto the human HCP S1200 midsurface [10].
Quantitative Analysis: For each laminar bin, receptor network fingerprints were created by z-scoring receptor densities and averaging them within functional regional networks defined by the Bezgin macaque functional atlas [3]. Differences in relative receptor densities across cortical layers were quantified by calculating correlations between receptor fingerprints.
To examine relationships between functional maps and receptor distributions, we implemented a 3-level hierarchical statistical analysis. First, multilinear regression was performed to test associations between activation maps and all whole-depth receptor maps. In the second stage, significant activation maps were correlated with whole-depth receptor maps. Finally, for receptor-functional map pairs significant in stage 2, laminar-specific correlations were calculated. P-values were calculated with permutation testing (1,000 permutations) using Brain Smash [10] and FDR corrected (5% false-positive rate).
Preprocessing: BrainBuilder was used to reconstruct 0.25 mm³ volumes for GABAA/B, AMPA, NMDA, Kainate, 5-HT1A, 5-HT2, M1, M2, M3, α1, and α2 receptors. Receptor densities were projected onto 18 cortical surfaces spanning the depth of the cortex, stratified into thirds (superficial, middle, and deep bins) and averaged. We applied surface smoothing (1mm FWHM) and averaged receptor densities across the 3 hemispheres to create 12 receptor maps x 3 depths through the cortex. Whole-depth receptor maps were also generated. Surfaces were transformed into Yerkes19 space[6,7] using MSM[8] and then to HCP human space via functional cross-species mapping[9].
Functional Mapping: 9 fMRI-derived functional maps were generated using neuroquery with the following keywords: association cortex, attention, auditory, emotion, executive, memory, motor, somatosensory, and visual. These maps were projected onto the human HCP S1200 midsurface [10].
Quantitative Analysis: For each laminar bin, receptor network fingerprints were created by z-scoring receptor densities and averaging them within functional regional networks defined by the Bezgin macaque functional atlas [3]. Differences in relative receptor densities across cortical layers were quantified by calculating correlations between receptor fingerprints.
To examine relationships between functional maps and receptor distributions, we implemented a 3-level hierarchical statistical analysis. First, multilinear regression was performed to test associations between activation maps and all whole-depth receptor maps. In the second stage, significant activation maps were correlated with whole-depth receptor maps. Finally, for receptor-functional map pairs significant in stage 2, laminar-specific correlations were calculated. P-values were calculated with permutation testing (1,000 permutations) using Brain Smash [10] and FDR corrected (5% false-positive rate).
Results:
Significant correlations (~-0.6 to 0.3) were observed between receptor and functional maps (Fig.1), with notable laminar differences. Serotonin receptors (5-HT1A/2) demonstrated a prominent role in executive and memory functions, particularly in the superficial and middle input layers. Similarly, ionotropic glutamate receptors (Kainate & AMPA) were strongly correlated with emotional processing, with higher correlations in the deeper output layers. Receptor network fingerprints also revealed laminar-specific differences (Fig.2), with a correlation of only 0.21 between superficial and deep layers. The insular-opecular and limbic networks had high densities of the 5HT1A receptor, indicating a role in emotional processing.
Conclusions:
We demonstrate a strong, layer-specific link between neurotransmitter receptor densities and functional domains/networks, with higher receptor densities in superficial layers. Notably, serotonin receptors in the superficial and middle layers are uniquely implicated in executive, memory, and emotional processing, while ionotropic glutamate receptors exhibit distinct laminar relationships related to emotional function.
Neuroanatomy, Physiology, Metabolism and Neurotransmission:
Anatomy and Functional Systems
Cortical Anatomy and Brain Mapping 1
Cortical Cyto- and Myeloarchitecture
Neuroinformatics and Data Sharing:
Brain Atlases 2
Keywords:
Atlasing
CHEMOARCHITECTURE
Cortical Layers
FUNCTIONAL MRI
GABA
Glutamate
Neurotransmitter
RECEPTORS
Seretonin
1|2Indicates the priority used for review
Abstract Information
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