Gradients of neurotransmitter receptor expression in the macaque cortex

Nat Neurosci. 2023 Jul;26(7):1281-1294. doi: 10.1038/s41593-023-01351-2. Epub 2023 Jun 19.

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Aged
  • Animals
  • Autoradiography
  • Brain Mapping*
  • Cerebral Cortex* / cytology
  • Cerebral Cortex* / metabolism
  • Cognition
  • Dendritic Spines
  • Female
  • Gyrus Cinguli / cytology
  • Gyrus Cinguli / metabolism
  • Humans
  • Macaca fascicularis
  • Male
  • Myelin Sheath / metabolism
  • Rats
  • Rats, Inbred Lew
  • Receptor, Serotonin, 5-HT1A / analysis
  • Receptor, Serotonin, 5-HT1A / metabolism
  • Receptors, Cholinergic / analysis
  • Receptors, Cholinergic / metabolism
  • Receptors, Dopamine / analysis
  • Receptors, Dopamine / metabolism
  • Receptors, Neurotransmitter* / analysis
  • Receptors, Neurotransmitter* / metabolism
  • Serotonin / metabolism
  • Species Specificity

Substances

  • Receptor, Serotonin, 5-HT1A
  • Receptors, Cholinergic
  • Receptors, Dopamine
  • Receptors, Neurotransmitter
  • Serotonin