Exp Brain Res (1987) 67:556-568 Experimental BrainResearch 9 Springer-Verlag 1987 A comparison between the connections of the amygdala and hippocampus with the basal forebrain in the macaque J.P. Aggleton, D.P. Friedman, and M. Mishkin Laboratory of Neuropsychology, National Institute of Mental Health, Building 9, Room 1N107, 9000 Rockville Pike, Bethesda, MD 20205, USA Summary. Autoradiographic experiments indicated that the amygdala projects to divisions Ch3 and Ch4 of the basal forebrain (nomenclature from Mesulam et al. 1983) and the olfactory tubercle. The heaviest of these amygdaloid outputs arose from the lateral basal, accessory basal, central, and medial amyg- daloid nuclei, each with a slightly different pattern of distribution from that of the other. Injections of the retrograde tracer horseradish peroxidase (HRP) into the amygdala revealed dense reciprocal projections arising from region Ch4, especially from subdivisions Ch4al, Ch4iv, and Ch4p. The other basal forebrain regions, by contrast, provided very little input to the amygdala. Hippocampal efferents terminated densely in the medial (Chl), lateral and dorsal septum, and in region Ch2. Hippocampal efferents terminated less densely in restricted portions of the olfactory tubercle and in Ch4. Experiments in which the fornix was transected showed that all of these hippocampal projections to the basal forebrain ran through the fornix. The hippocampal output to the septum, which was the heaviest projection of those examined, appears to have a crude topographic arrangement. Little overlap was observed between the terminal zones of the amygdaloid and hippocam- pal projections to the basal forebrain, indicating yet again the independence of the amygdaloid and hip- pocampal systems that has been demonstrated in other regions of the forebrain, such as the thalamus and cerebral cortex. Key words: Amygdala - Hippocampus - Forebrain - Macaque Offprint requests to: J.P. Aggleton, Department of Psychology, University of Durham, Science Laboratories, South Road, Durham DH1 3LE, U.K. Introduction There is increasing evidence that damage to the basal forebrain, and in particular the basal nucleus of Meynert, is a critical feature of Alzheimer's disease (Whitehouse et al. 1982; Candy et al. 1983; Coyle et al. 1983). As some of the earliest symptoms of Alzheimer's disease involve changes in memory and affect, it is of particular interest that the basal forebrain has substantial direct connections with limbic structures such as the hippocampal formation and the amygdaloid complex (Mesulam and Mufson 1984; Russchen et al. 1985). The aim of the present study was to examine the direct connections between the basal forebrain and these two limbic structures in detail. The efferent projections from the amygdala and hippocampus were traced by placement of injections of tritiated amino acids into each structure. The hippocampal injections were concentrated in the subicular cortex, as it is this region that provides efferents running beyond the septal area (Rosene and Van Hoesen 1977; Swanson and Cowan 1977). Because fornix transection does not abolish the ability of hippocampal stimulation to modify the firing rate of units in the basal forebrain (Poletti and Sujatanond 1980), we also investigated whether any hippocampal efferents to the septum or basal fore- brain run in pathways other than the fornix. This was accomplished by injections of isotope into the hip- pocampal formation of animals with fornical transec- tions. Although it is known that the basal forebrain projects to the amygdala (Aggleton et al. 1980; Mesulam et al. 1983), there is little information concerning the precise source of these reciprocal connections. We examined these projections in detail by tracing the retrograde transport of horseradish peroxidase (HRP) placed in the amygdala. The