~ Pergamon 0306-4522(95)00417-3 Neuroscience Vol. 71, No. I, pp. 5~75, 1996 Elsevier Science Ltd Copyright © 1996 IBRO Printed in Great Britain. All rights reserved 0306-4522/96 $15.00 + 0.00 A PROJECTIONS OF THE MEDIAL AND LATERAL PREFRONTAL CORTICES TO THE AMYGDALA: PHASEOLUS VULGARIS LEUCOAGGLUTININ STUDY IN THE RAT A. J. MCDONALD,* F. MASCAGNI and L. GUO Department of Cell Biology and Neuroscience, University of South Carolina School of Medicine, Columbia, SC 29208, U.S.A. Abstract--The projections of different subfields of the medial and lateral prefrontal cortices to the amygdala were studied in the rat using the sensitive Phaseolus vulgaris leucoagglutinin anterograde tract tracing technique. Injections into the infralimbic cortex produced anterograde labeling in the lateral capsular subdivision of the central nucleus, superficial (corticomedial) amygdaloid nuclei, lateral and accessory basal nuclei, and the anterior amygdaloid area. Injections into the caudal portion of the infralimbic cortex produced additional labeling in the intermediate subdivision of the central nucleus. The prelimbic cortex had projections to the medial portion of the magnocellular basal nucleus and adjacent portions of the lateral nucleus and lateral capsular subdivision of the central nucleus. The medial preoentral cortex had projections to the rostromedial part of the magnocellular basal nucleus and adjacent portions of the lateral capsular subdivision of the central nucleus. Injections into the lateral orbital and ventral agranular insular cortices produced labeled fibers in the rostral part of the superficial amygdala, lateral capsular subdivision of the central nucleus, and the lateral and accessory basal nuclei. The dorsal agranular insular area had projections to several different subdivisions of the central nucleus as well as to the rostrolateral magnocellular basal nucleus; the latter projections were complementary to those originating in the prelimbic area. The present study indicates that each portion of the prefrontal cortex has a distinctive projection to the amygdala. The ventral areas of the lateral and medial prefrontal cortices, which receive olfactory projections, are the only prefrontal cortical areas with projections to the olfactory-related superficial amygdaloid nuclei. The more dorsally situated prefrontal areas, the dorsal agranular insular area and prelimbic cortex, have complementary projections to the basal nucleus, suggesting that they modulate separate prefrontal cortico-striatal-pallidal circuits. The specificity of prefrontal cortico-amygdaloid projections is indicative of their involvement in discrete functions. Key words: frontal cortex, anterograde tract tracing. The general function of the amygdala is to evaluate the significance of sensory stimuli and to generate appropriate emotional responses by coordinating the activity of brain areas controlling autonomic, endo- crine, and somatomotor mechanisms. ~7,37"52 This pro- cess involves associating sensory stimuli with their affective attributes. Research in primates indicates that the connections of the amygdala with the pre- *To whom correspondence should be addressed. Abbreviations: ACd, dorsal anterior cingulate cortex; Aid, dorsal agranular insular cortex; AI,, ventral agranular insular cortex; B-A, accessory basal nucleus of the amygdala; Bin, basal magnocellular amygdaloid nu- cleus; B~, basal parvicellular amygdaloid nucleus; CI, intermediate subdivision of the central amygdaloid nu- cleus; CLC, lateral capsular subdivision of the central amygdaloid nucleus; CM, medial subdivision of the central amygdaloid nucleus; HRP, horseradish peroxi- dase; IL, infralimbic cortex; Lv, ventromedial subdivi- sion of the lateral amygdaloid nucleus; PHA-L, Phaseolus vulgaris leucoagglutinin; PL, prelimbic cortex; PrCm, medial precentral cortex. frontal cortex are essential for learning these stimu- lus-reinforcement associations and for modifying responses in the face of changing reinforcement contingencies. 14,15,67 Recent analyses of forebrain circuitry in primates and rodents indicate that there exist multiple, parallel cortico-striato-pallido-thalamic circuits that have dis- crete functions. 1,19,20The amygdala has extensive con- nections with the structures of the "limbic circuit", consisting of the following structures connected in sequence: prefrontal cortex, limbic striatum, ventral pallidum and mediodorsal thalamic nucleus, t9,2°,6° This circuit appears to be involved with behavior related to emotion, motivation and reward, 24'6s'7°and it has been suggested that disturbances in the function of this circuit may be associated with schizophrenia and other affective disorders. TM Studies in rodents have shown that the limbic circuit consists of a number of subcircuits associated with distinct pre- frontal areas. 19,2° Recent anatomical investigations indicate that discrete portions of the amygdala pro- 55