Cholecystokinin innervation of monkey prefrontal cortex: an immunohistochemical study

Knowledge of the circuitry of chemically identified systems in primate prefrontal cortex is limited. Although cholecystokinin is very abundant in prefrontal cortex (Geola et al.: Journal of Clinical Endocrinology and Metabolism 53(2):270-275, 1981; Taquet et al.: Neuroscience 27(3):871-883, 1988), the organization of cholecystokinin-containing structures in primate prefrontal cortex has not been investigated. Using immunohistochemical and retrograde transport techniques, we characterized the cholecystokinin innervation of prefrontal cortex in macaque monkeys. The use of two antibodies directed against different portions of the cholecystokinin molecule revealed that distinct forms of the molecule were differentially localized in the same cortical neurons. These small, nonpyramidal cholecystokinin-positive neurons had a variety of somal morphologies and the density of labeled cells did not differ among cytoarchitectonic regions. Labeled neurons had a distinctive laminar distribution with the greatest density of cells present in layers II-superficial III. Labeled fibers also had a distinctive laminar pattern of distribution that differed from that of the immunoreactive neurons. In granular prefrontal cortex, terminal fields were evident in layers II, IV, and VI, with the greatest density in layer VI. Agranular area 24 exhibited a bilaminar pattern of immunoreactivity with a band in layer II and a very dense terminal field in layers V-VI. A high density of cholecystokinin-binding sites has been found in layers III-IV of prefrontal cortex and other association areas in the monkey; this finding has been attributed to possible cholecystokinin-containing afferents from the thalamus (Kritzer et al.: Journal of Comparative Neurology 263:418-435, 1987). The mediodorsal nucleus of the thalamus is known to be a source of afferents which terminate in layer IV of prefrontal cortex. However, combined retrograde transport and immunohistochemical techniques failed to reveal the presence of cholecystokinin-positive neurons in the mediodorsal nucleus of the thalamus that project to prefrontal cortex. These findings, and other observations, suggest that the terminal field in layer IV is formed by descending axons that arise from cholecystokinin-containing neurons in layers II and superficial III. This study demonstrates that the cholecystokinin innervation of prefrontal cortex has a laminar specific organization that is preserved across cytoarchitectonic regions. This distribution of immunoreactive structures suggests a distinctive role of cholecystokinin in cortical circuitry that is common to every region of prefrontal cortex.