Research reportEfferent projections of infralimbic and prelimbic areas of the medial prefrontal cortex in the Japanese monkey, Macaca fuscata
Introduction
The medial and ventral parts of the frontal lobe of the monkey can modulate autonomic parameters [21], [41], [59] and the role of the ventromedial frontal lobe in autonomic function is that individuals with lesions of this area are unable to generate autonomic responses to emotional stimuli. Remarkably, they are also impaired in making judgments about the consequences of their actions in social situations, despite possessing the knowledge necessary to make the correct decision [9], [18], [19]. Damasio and his co-workers [19] have suggested that these two deficits are related and that the sociopath-behavior of these patients is due to their inability to generate ‘somatic markers’ that tag behavioral options as desirable or not [10]. The frontal lobe damage would lead to loss of affective responsiveness and foresight arising from interoceptive agnosia [32]. Damasio [18] extended this concept to explain the ‘acquired sociopathy’ of patients with bilateral orbitofrontal damage.
The viscerosensory and visceromotor areas in the frontal lobe are suggested to be localized in the agranular insular, infralimbic and prelimbic cortex (IL and PL). The viscerosensory inputs reach specific areas within the agranular insula in primates as in rodents [14]. Thus, IL and PL have been postulated to be an autonomic motor area in the medial prefrontal cortex (PFC), as efferent and afferent connections of IL in the rat were examined by several workers and IL and PL were found to be reciprocally connected with most central autonomic nuclei as far as the spinal cord in the rat [5], [4], [27], [54].
As recent studies revealed, the cytoarchitectonic map and histochemical characteristics of the monkey PFC including IL and PL [14], we designed the present study so as to reveal the projection sites of the medial PFC of the monkey, Macaca fuscata, using biotinylated dextran amine (BDA) as an anterograde tracer. The injection sites covered PL, IL and the adjacent medial PFC including area 14, and area 24b. We concentrated on the projection pattern of IL compared with PL in this study. Part of the present studies were presented as preliminary reports on several occasions [17], [38], [39]. During the preparation of this manuscript, two important results of projection studies of the medial prefrontal cortex of macaque monkeys, Macaca fascicularis and Macaca nemestrina, were reported [3], [43]. The major results were similar to ours except for a few different findings and the present results were carefully compared and discussed with those of their studies. We used BDA as a marker useful for precisely identifying the injection sites and also followed very thin axons of the autonomic neurons in the central nervous system for a considerable distance.
Section snippets
Materials and methods
Ten adult Japanese monkeys, Macaca fuscata, of both sexes and 3.5–5.5 kg body weight were used in the present study. All animal protocols were reviewed and approved by the Animal Studies Committee of Mie University. The animals were anesthetized with intramuscular injection of ketamine hydrochloride (10 mg/kg) and then with pentobarbital (25 mg/kg). The animals were fixed on stereotaxic apparatus, and 0.1–1.0 μl×1–3 times of 5% biotinylated dextran amine (BDA, 10 000 MW, Molecular Probes Inc.)
Injection sites
From a series of BDA injections into the medial prefrontal cortex of monkeys, seven cases were selected for the present analyses of the projection pattern of the medial prefrontal cortex including the anterior cingulate cortex (area 24b), IL (area 25) and PL (area 32). Injection sites were identified by the distribution of pyramidal cells labeled by the uptake of injected BDA, reconstructed from the serial frontal sections and were projected to the saggital plane of the medial prefrontal cortex
Methodological considerations
The present study using BDA as an anterograde tracer clearly demonstrated the distribution of labeled perikarya and dendrites in the injection sites of mPFC, and axons and terminal arborizations with varicosities in the projected areas. The axons of autonomic and limbic nervous systems were extremely thin and it was difficult to identify the labeled ones with a low magnification microscope, but were able to observe them at higher magnifications even if they were scattered in a few fiber bundles
Acknowledgements
We are grateful to Ms. E. Takahashi, Dr. T. Takeda and Ms. K. Kitajo for their excellent technical assistance. The present study was supported by the grant-in-aid from the Ministry of Education, Science, Sports and Culture of Japan to T. Chiba.
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