Psychobiology 1999,27 (2), 149-164 Hippocampal and amygdaloid interactions in the nucleus accumbens HENKJ.GROENEWEGEN Vrije Universiteit, Amsterdam, The Netherlands ANTONIUS B. MULDER University ofAmsterdam, Amsterdam, The Netherlands ARNO V. J. BEIJER and CHRISTOPHER I. WRIGHT Vrije Universiteit, Amsterdam, The Netherlands FERNANDO H. WPES DA SILVA University ofAmsterdam, Amsterdam, The Netherlands and CYRIEL M. A PENNARTZ Netherlands Institute for Brain Research, Amsterdam, The Netherlands The nucleus accumbens, in view of its afferent and efferent fiber connections, appears to hold a key position for "limbic" (e.g., hippocampal and amygdaloid) influences to reach somatomotor and auto­ nomic brain structures, and it has therefore been considered as a limbic-motor interface. The nucleus accumbens can be subdivided into a shell and a core region, which both contain further inhomo­ geneities. The present account first summarizes the detailed topographical anatomical relationships of inputs from different dorso-ventral parts of the hippocampus and different rostrocaudal parts of the basal amygdaloid complex at the level of the accumbens. Subsequently, the electrophysiological char­ acteristics of hippocampal and amygdaloid inputs in the accumbens are described. Interactions be­ tween hippocampal and amygdaloid inputs appear to exist primarily in the medial parts of both the shell and the core of the nucleus accumbens. In the short term, stimulating amygdaloid inputs appear to facilitate hippocampal throughput (heterosynaptic paired pulse facilitation), whereas stimulation of hippocampal inputs depresses amygdaloid throughput in a paired pulse paradigm. Tetanic stimulation of hippocampal inputs to the accumbens leads to a decrementallong-term potentiation (LTP) of this fiber pathway (homosynaptic LTP) but, along a similar time range, to a depression of amygdaloid in­ puts (heterosynaptic long-term depression). The involvement of dopaminergic, GABAergic, and gluta­ matergic mechanisms in these interactions is discussed. Finally, it is suggested that the interactions be­ tween hippocampal and amygdaloid inputs at the level of the nucleus accumbens playa role in different aspects of associative learning. The nucleus accumbens (Acb) is a brain area located striatum, which further includes the ventromedial parts in the rostroventral part of the basal forebrain. Following of the caudate-putamen complex and the striatal elements the seminal paper by Heimer and Wilson in 1975, the Acb of the olfactory tubercle. The ventral striatum in general, has been considered a component of the so-called ventral and the Acb in particular, is thought to be involved in var­ ious complex behavioral functions, including sensori­ motor, motivational, and adaptational processes (Cador, The authors wish to thank Wil 1. A. J. Smeets for his critical comments Robbins, & Everitt, 1989; Everitt, Morris, O'Brien, & on the paper, Martijne Mendes-de Leon and Jolinda Kos for secretarial Robbins, 1991; Groenewegen, Berendse, Wolters, & Loh­ assistance, and Dirk de Jong for his photographic contribution. A.B.M. man, 1990; Groenewegen, Wright, & Beijer, 1996; Mogen­ was in the Institute for Neurobiology at the University of Amsterdam son, Jones, & Yim, 1980; Pennartz, Groenewegen, & at the time of this research; he is now at the Netherlands Institute for Lopes da Silva, 1994; Scheel-KrUger & Willner, 1991; Brain Research. A.Y.1.B. is in the Research Institute Neurosciences, De­ partment of Anatomy at the Vrije Universiteit, as was C.1. W. when this Zahm & Brog, 1992). Further, the Acb plays a prominent research was done; C.I.w. is now at the Department of Neurology, Har­ role in reward learning, and this nucleus has been impli­ vard Medical School, Brigham and Women's Hospital, Boston. F.H.L.S. cated in schizophrenia and other affective disorders, as well is in the Institute for Neurobiology at the University of Amsterdam. as in drug abuse (Koob, 1992; Robbins & Everitt, 1996). Correspondence should be addressed to H. 1. Groenewegen, Depart­ ment of Anatomy, Faculty of Medicine, Vrije Universiteit, Van der Boe­ In terms offiber connections, the Acb is characterized chorststraat 7, 1081 BT Amsterdam, the Netherlands (e-mail: hj.groe­ by strong inputs from limbic lobe-related structures, such [email protected]). as the hippocampal formation, basal amygdaloid complex, 149 Copyright 1999 Psychonomic Society, Inc. 150 GROENEWEGEN ET AL. parahippocampal cortex, and anterior cingulate cortex. (Groenewegen et aI., 1987). Amygdalostriatal projections Other inputs are derived from the prefrontal cortex, the have a much more widespread distribution than the hippo­ midline thalamic nuclei, the dopaminergic ventral teg­ campostriatal fibers and include extensive parts of the mental area and the serotonergic median raphe nucleus caudate-putamen complex (Kelley et aI., 1982; Kita & (Brog, Salyapongse, Deutch, & Zahm, 1993; Groenewe­ Kitai, 1990; Wright et aI., 1996). However, the Acb is gen, Becker, & Lohman, 1980; Groenewegen, Room, Wit­ reached by almost all parts ofthe basal amygdaloid com­ ter, & Lohman, 1982; Groenewegen, Vermeulen-Van der plex in a highly topographical way (Wright et aI., 1996). Zee, te Kortschot, & Witter, 1987; Kelley & Domesick, Thus, the Acb is a main potential convergence site of hip­ 1982; Kelley, Domesick, & Nauta, 1982; Newman & pocampal and amygdaloid influences on the basal gan­ Winans, 1980; Phillipson & Griffiths, 1985; Totterdell glia and, through the output of these structures, on be­ & Meredith, 1997). It projects, in turn, to various behav­ havioral functions. The hippocampal formation and ioral effector regions such as the ventral pallidum, the lat­ amygdala are thought to be involved in different aspects eral hypothalamus, the ventral tegmental area, the sub­ of certain behaviors. The amygdala, in forming stimulus­ stantia nigra pars compacta and caudal mesencephalic reward and stimulus-punishment associations, serves as areas, including the so-called mesencephalic locomotor a link between sensory systems and structures involved region, and adjacent, lateral parts of the central gray sub­ in the expression of emotional behavior (Adolphs, Tranel, stance (Berendse, Groenewegen, & Lohman, 1992; Damasio, & Damasio, 1995; Davies, 1992; Everitt et aI., Heimer, Zahm, & Alheid, 1995; Heimer, Zahm, Churchill, 1991; LeDoux, 1993). The hippocampal formation is im­ Kalivas, & Wohltmann, 1991; Nauta, Smith, Faull, & portant for memory functions, particularly those involving Domesick, 1978). The Acb appears to hold a key position spatial cues (Alvarez, Zola-Morgan, & Squire, 1995; Zola­ in the pathways by which motivational and emotional in­ Morgan, Squire, Alvarez-Royo, & Clower, 1991; Zola­ fluences reach somatomotor and autonomic brain struc­ Morgan, Squire, & Amaral, 1986, 1989). Interestingly, tures. In this respect, the nucleus has been considered a manipulations of either the hippocampal or the amygda­ limbic-motor interface (Groenewegen et aI., 1996; Mo­ loid systems, through the Acb, have led to different, and genson et aI., 1980). in some instances opposing, effects on behavior (e.g., lo­ The Acb has long been treated as a homogeneous struc­ comotor activity; for a review, see Pennartz et aI., 1994). ture, but recently it has been recognized that the Acb con­ In view of the topographical organization of both the sists of various subdivisions. Most notably, a peripherally hippocampal and amygdaloid inputs to the Acb, the in­ located "shell" and a centrally located "core" region have trinsic heterogeneity of the nucleus, and the differential been recognized (Voorn, Gerfen, & Groenewegen, 1989; behavioral roles of the hippocampal formation and amyg­ Zaborszky et aI., 1985; Zahm & Brog, 1992). This bipar­ dala, the present paper provides a brief review of the ana­ tition of the nucleus is primarily based on the differential tomical and physiological relationships between these histochemical characteristics of the shell and core. Results two limbic inputs at the level of the Acb. Unless otherwise of neuroanatomical tracing studies indicate that the var­ specified, the descriptions below relate to data obtained ious afferent systems ofthe Acb appear to be inhomoge­ in rats. neously distributed over the nucleus, forming an intricate pattern that to a certain degree is related to the shell-core ANATOMICAL RELATIONSHIPS BETWEEN subdivision. Likewise, populations of output neurons that HIPPOCAMPAL AND AMYGDALOID project to the various targets of the Acb appear to be in­ INPUTS IN THE NUCLEUS ACCUMBENS homogeneously distributed over the nucleus (Berendse et aI., 1992; Groenewegen et aI., 1996; Heimer et aI., 1997; Immunohistochemical and Cytoarchitectonic Herkenham, Moon-Edley, & Stuart, 1984). Moreover, re­ Framework of the Nucleus Accumbens sults of numerous pharmacological and behavioral studies The differential distribution of immunoreactivity for have revealed that there are major functional differences the calciumbinding protein Calbindin DZ8K (CaB) pro­ between Acb shell and core (e.g., Deutch & Cameron, vides the generally accepted means of subdividing the 1992; Kelley, Smith-Roe, & Holahan, 1997; Parkinson, Acb into a shell and a core region (longen-Relo, Voorn, Olmstead, Bums, Robbins, & Everitt, 1999; Stratford & & Groenewegen, 1994; Zahm & Brog, 1992; Figure 1). Kelley, 1997; Weiner, Gal, Rawlins, & Feldon, 1996). For the subsequent description of the termination pat­ One of the most distinguishing features of the Acb is terns of hippocampal