Pergamon 0306-4522(94)00629-6 Neuroscience Vol. 66, No. 4, pp. 959-982, 1995 Elsevier ScienceLtd Copyright © 1995 IBRO Printed in Great Britain. All rights reserved 0306-4522/95 $9.50 + 0.00 NEUROPEPTIDE Y AND SOMATOSTATIN-LIKE IMMUNOREACTIVITY IN NEURONS OF THE MONKEY AMYGDALA A. J. MCDONALD,* F. MASCAGNI and J. R. AUGUSTINE Department of Cell Biology and Neuroscience, University of South Carolina School of Medicine, Columbia, SC 29208, U.S.A. Akstraet--Neurons in the monkey amygdala exhibiting neuropeptide Y-like immunoreactivity and somatostatin-like immunoreactivity were identified using an avidin-biotin immunohistochemical tech- nique. Differential co-existence of the two peptides was demonstrated using two-color immunoperoxidase and adjacent section methods. Numerous neuropeptide Y-positive neurons were observed in the basolateral and superficial amygdaloid nuclei. A moderate number of neuropeptide Y-positive neurons was seen in the medial subdivision of the central nucleus, but only a few neurons were observed in the lateral subdivision. Numerous somatostatin-positive neurons were stained in all major amygdaloid nuclei and always outnumbered neuropeptide Y-positive cells. All amygdaloid nuclei contained numerous peptide-positive fibers whose density varied depending on the nucleus. Approximately 90% of neuro- peptide Y-positive neurons also exhibited somatostatin-like immunoreactivity. The percentage of somatostatin-positive neurons that exhibited neuropeptide-Y immunoreactivity varied in different nuclei. In the superficial amygdaloid nuclei, medial subdivision of the central nucleus and most portions of the basolateral nuclei the predominant cell type stained with both the neuropeptide Y and somatostatin antibodies was a spine-sparse non-pyramidal neuron. In the dorsal portion of the lateral nucleus, however, most peptide-positive neurons had spiny dendrites. Only the cell bodies and proximal dendrites of somatostatin-positive neurons in the lateral subdivision of the central nucleus were immunostained. This study demonstrates that specific cell populations in the primate amygdala contain neuropeptide Y, somatostatin or both peptides. Most peptide-positive neurons in the basolateral and superficial amygdaloid nuclei appear to be local circuit neurons that contribute to the dense plexus of peptide-positive axons in these regions. The finding of neurons with spiny dendrites in the dorsal part of the lateral nucleus suggests that these cells may be functionally different from peptide-positive neurons in other portions of the basolateral amygdala. The lateral subdivision of the central nucleus is distinguished from other amygdaloid nuclei by containing a large population of somatostatin-positive neurons that do not exhibit neuropeptide Y immunoreactivity. Neuropeptide Y (NPY) is a 36-amino acid peptide that appears to act as a neuromodulator in the central and peripheral nervous systems. 14'15'31'37'57'59 It is the most abundant peptide in the brain and is especially plentiful in the amygdala, 1'4 suggesting that NPY may play an important role in modulating the activity of amygdaloid neurons involved in behavioral, affective and mnemonic functions. Immunohistochemical studies in the rat have shown that the amygdala contains a dense plexus of NPY-containing axons and a moderate number of NPY-containing perikaryaJ 3'28 Although mapping studies of the fore- brain in the squirrel monkey 66 and human 73 have demonstrated that there are NPY-containing cells *To whom correspondence should be addressed. Abbreviations: BDHC, benzidine dihydrochloride; CL, lateral subdivision of the central nucleus; CM, medial subdivision of the central nucleus; DAB, 3,3"-di- aminobenzidine; Ld, dorsal portion of the lateral nucleus; Lv, ventral portion of the lateral nucleus; NADPH, reduced nicotinamide adenine dinucleotide phosphate; NPY, neuropeptide Y; PBS, phosphate- buffered saline. and fibers in the primate amygdala, there have been no comprehensive, detailed investigations of these neuronal elements. The peptide neuromodulator somatostatin was first isolated from ovine hypothalamus and shown to be a cyclic peptide consisting of 14 amino acids (somatostatin-14). 8 Subsequent studies revealed the existence of an N-terminally extended form of somatostatin consisting of 28 amino acids (somato- statin-28) and a related peptide consisting of the first 12 amino acids of the N-terminal of somatostatin-28 (somatostatin-28~ 12). 6'21 Previous studies of somato- statin immunoreactivity in the amygdala of non- human primates have utilized antibodies to somato- statin-28~ 12 and the N-terminal segment of somatostatin-28. 2'j7 There have been no studies using antibodies that recognize somatostatin-14, the main form of somatostatin present in the mammalian brain. 2° Immunohistochemical co-localization studies have demonstrated that virtually all NPY-containing neurons in the rat amygdala also contain somato- statin, but the percentage of somatostatin neurons 959