Gradients of neurotransmitter receptor expression in the macaque cortex

Abstract

Dynamics and functions of neural circuits depend on interactions mediated by receptors. Therefore, a comprehensive map of receptor organization across cortical regions is needed. In this study, we used in vitro receptor autoradiography to measure the density of 14 neurotransmitter receptor types in 109 areas of macaque cortex. We integrated the receptor data with anatomical, genetic and functional connectivity data into a common cortical space. We uncovered a principal gradient of receptor expression per neuron. This aligns with the cortical hierarchy from sensory cortex to higher cognitive areas. A second gradient, driven by serotonin 5-HT1A receptors, peaks in the anterior cingulate, default mode and salience networks. We found a similar pattern of 5-HT1A expression in the human brain. Thus, the macaque may be a promising translational model of serotonergic processing and disorders. The receptor gradients may enable rapid, reliable information processing in sensory cortical areas and slow, flexible integration in higher cognitive areas.

Distributed evidence accumulation across macaque large-scale neocortical networks during perceptual decision making

“…This ensures that each cortical area was unique in its configuration and dynamics, and reflected the high level of neural and circuit heterogeneity found in real brains. The area-specific properties revealed macroscopic gradients across cortex (Wang, 2020), and included variations in the effective strength of synapses inferred from local properties such as the number of dendritic spines per pyramidal cell (Elston, 2007; Mejias and Wang, 2022) and the area-specific density of NMDA and GABA A receptors per neuron (Froudist-Walsh et al, 2023b, 2023a)(Figure 1B).…”

Cytoarchitectonic and connection stripes in the dysgranular insular cortex in the macaque monkey

“…Future studies will continue to refine our understanding of the insula, hopefully improving toward anatomically and functionally relatable and less ambiguous partition. Recent advanced enabling, for example, the combination of classical cytoarchitectonics or tract tracing with neurotransmitter receptor mapping (Froudist-Walsh et al, 2023) or high-density single-cell spatial mapping of the expression of hundreds of genes (Chen et al, 2023), could help support or instead simplify the dysgranular parcellations. High-resolution neuroimaging capturing the curved surface of the insula (Goense & Logothetis, 2006;Zhu & Vanduffel, 2019) and high-density electrode arrays implanted across different stripes of the insula could verify and reveal their functional implications.…”

A computational account of joint SSRI and anti-inflammatory treatment

“…The excitatory long-range reciprocal interaction between the PFC and SCC is depicted in Figure 1C (right panel). In general, receptor expression varies systematically across cortical areas [Froudist-Walsh et al 2023]. Among all receptors, serotonin shares the most marked change (gradient) in expression over the cortex.…”