Gradients of receptor expression in the macaque cortex

Abstract

Dynamics and functions of neural circuits depend on synaptic interactions mediated by receptors. Therefore, a comprehensive map of receptor organization is needed to understand how different functions may emerge across distinct cortical regions. Here we use in-vitro receptor autoradiography to measure the density of 14 neurotransmitter receptor types in 109 areas of macaque cortex. We integrate the receptor data with other anatomical, genetic and functional connectivity data into a common cortical space. We uncovered a principal gradient of increasing receptor expression per neuron aligned with cortical hierarchy from early sensory cortex to higher cognitive areas. A second gradient, primarily driven by 5-HT1A receptors, peaks in the anterior and subcallosal cingulate, suggesting that the macaque may be a promising animal model for major depressive disorder. The receptor gradients may enable rapid, reliable information processing in sensory cortical areas and slow, flexible integration of information in higher cognitive areas.

Mapping neurotransmitter systems to the structural and functional organization of the human neocortex

“…The present study is an ongoing Open Science grassroots effort to assemble harmonized high-resolution normative images of receptors and transporters that can be used to annotate connectomic models of the brain. This work builds on previous initiatives to map receptor densities using autoradiography, which has discovered prominent gradients of receptor expression in both human and macaque brains [36,46,145]. Importantly, we find consistent results between autoradiography and PET datasets, which is encouraging because the PET dataset consists of a dif-ferent group of receptors and transporters, and has the added advantage of providing in vivo whole-brain data in large samples of healthy young participants.…”

“…We find a prominent spatial gradient of receptor profiles that separates areas involved in extrinsic function, including sensory-motor processing and attention, versus areas involved in affect and interoception. This gradient maps on to the sensory-fugal synaptic hierarchy proposed by Mesulam [36,69]. The concordance between the two maps is noteworthy because one is derived from the wiring patterns of the brain, while the other is derived from mapping receptors to task-based activations.…”

A dopamine gradient controls access to distributed working memory in the large-scale monkey cortex

“…Much less is known about the influence of these and other neuromodulators on the distributed network activity that underlies working memory outside of the prefrontal cortex. Future work should focus on the interaction of distinct neuromodulators and how release of different combinations of neuromodulators may affect distributed activity patterns and behavior, taking into account the different distributions of these receptors across the cortex (Froudist-Walsh et al, 2021). Subcortical structures, such as the thalamus, may play a significant role in working memory (Fuster and Alexander, 1971;Guo et al, 2017;Jaramillo, et al, 2019;Watanabe and Funahashi, 2012).…”

Spatial signatures of anesthesia-induced burst-suppression differ between primates and rodents

“…The visual cortex of primates could impose special metabolic demands and thus find itself at an extreme end of the spectrum for burst propensity. Such special demands could arise from its many distinctive characteristics-including cytoarchitecture, neurotransmitter receptor expression (Froudist-Walsh et al, 2021), functional connectivity profile (Margulies et al, 2016), and cortical myelin density (Essen et al, 2019). We particularly suspect cortical myelin to play a role, considering that many areas excluded from our primate burst-suppression maps-V1, MT, primary motor, and somatosensory cortices-are among the richest in myelin (Essen et al, 2019).…”