On lateral septum-like characteristics of outputs from the accumbal hedonic “hotspot” of Peciña and Berridge with commentary on the transitional nature of basal forebrain “boundaries”

The accumbens (Acb), an input structure of the ventral striatopallidum (Heimer and Wilson, 1975), comprises core, shell (Zaborszky et al., 1985; Heimer et al., 1991b), and rostral pole (Zahm and Brog, 1992; Heimer and Zahm, 1993) subterritories variably concerned with mechanisms of locomotor activation, novelty detection, reward anticipation, and response reinforcement (Kelly et al., 1975; Schultz et al., 1997; Wise, 2004; Zahm, 2000, 2008). The Acb also contributes to hedonic-aversive controls on ingestive behavior. Infusion of μ-opioid receptor agonist into the Acb stimulates vigorous feeding in sated rats (Mucha and Iversen, 1986; Evans and Vaccarino, 1990; Bakshi and Kelley, 1993; Kelley et al., 1996, 2002), which has suggested to some researchers that the release of opioid peptides in the Acb mediates, at least in part, the rewarding or pleasurable attributes of feeding (Cooper and Kirkham, 1990; Evans and Vaccarino, 1990). Consistent with this notion, injection of the μ-opioid receptor agonist DAMGO (D-ala2-N-Me-Phe4-Glycol5-enkephalin) selectively into the rostrodorsal part of the medial shell of the accumbens (rdAcbSh ) significantly promotes the expression of hedonic “liking” responses emitted by rats in response to the taste of an appetitive sucrose solution (Pecina and Berridge, 2005). Similarly, a conditioned place preference and stimulated intake preferentially of appetitive food accompanies intra-Acb infusion of muscimol, a γ-aminobutyric acid–A type (GABAA) receptor agonist, or DNQX (6,7-dinitroquinoxaline-2,3(1H,4H)-dione), an antagonist of the glutamate AMPA (alpha-amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid)-kainate receptor (Reynolds and Berridge, 2001, 2002, 2003). Berridge and colleagues accordingly referred to the effective site, which is coextensive with the rdAcbSh, as a hedonic “hot spot” (Pecina and Berridge, 2005; Pecina et al., 2006; Faure et al., 2010). In contrast, infusion of these compounds into the caudodorsal quadrant of the medial shell of the Acb (cdAcbSh) produced suppression, not only of hedonic “liking” responses to sucrose, but also “disliking” responses to quinine. Injections of muscimol and DNQX into the cdAcbSh also incited rats to fearful posturing and defensive actions such as treading and burying (Reynolds and Berridge, 2001, 2002). The functional specificity observed by Berridge and colleagues would not readily be predicted from Acb inputs, which, throughout the Acb, including the rdAcbSh, come from the same collection of structures, mainly the basal amygdala, subiculum, prefrontal cortex, midline, and intralaminar thalamic nuclei and midbrain dopaminergic and serotoninergic complexes (McGeorge and Faull, 1989; Brog et al., 1993; Voorn et al., 2004). The basic organization of Acb is such that the combination of inputs to any of its parts differs only topographically from that to adjacent parts. This remains true despite the fact that in some parts of the Acb afferents terminate in complicated patterns of overlapping and nonoverlapping patches (Pennartz et al., 1994) of which input–output relationships are but partially worked out (e.g., Berendse et al., 1992). The cdAcbSh is exceptional in receiving some inputs not present in other parts of the Acb that ascend from the caudal brainstem and rostral spinal cord (Cliffer et al., 1991; Brog et al., 1993; Delfs et al., 1998; Brown and Moliver, 2000). In addition, the cdAcbSh merges without perceptible boundary with the bed nucleus of stria terminalis, a part of the extended amygdala (Alheid and Heimer, 1989; Heimer et al., 1991b; Heimer and Alheid, 1991; Zahm, 1998). Outputs from the Acb likewise are both topographically (Swanson and Cowan, 1975; Conrad and Pfaff, 1976; Powell and Leman, 1976; Williams et al., 1977; Troiano and Seigel, 1978; Nauta et al., 1978; Mogenson et al., 1983; Groenewegen and Russchen, 1984; Haber et al., 1990; Heimer et al., 1991; Zahm and Heimer, 1993; Kirouac and Ganguly, 1995; Usuda et al., 1998) and compartmentally (Berendse et al., 1992) organized. Those originating in dorsal and lateral parts of the Acb, mainly in the core subterritory, project in topographic fashion to the ventromedial globus pallidus, ventral pallidum, subthalamic nucleus, and substantia nigra in a quite basal ganglia-like manner (Zahm and Heimer, 1990, 1993; Heimer et al., 1991b; Usuda et al., 1998). Projections from the Acb medial shell similarly ramify in a very dense, basal ganglia-like fashion within the ventral pallidum, but then, in a manner uncharacteristic of any “classical” basal ganglia structure, descend in the medial forebrain bundle through the lateral preoptic area, lateral hypothalamus, ventral mesencephalon, midbrain paramedian zone, and periaqueductal gray (Nauta et al., 1978; Groenewegen and Russchen, 1984; Heimer et al., 1991b; Heimer and Zahm, 1993; Usuda et al., 1998). Within all of these structures descending Acb fibers are decorated with moderate numbers of axonal varicosities, signifying likely synaptic function. Interestingly, the connections of the part of the Acb lately designated as a hedonic “hotspot” were not singled out for special attention in earlier neuroanatomical literature, and thus the striking functional specificity reported by Berridge and colleagues may have a heretofore unrecognized anatomical correlate. Accordingly, we undertook to examine these connections and observed that the rdAcbSh and lateral septum are reciprocally interconnected and outputs from the rdAcbSh converge in the lateral preoptic area with those of the lateral septum. These relationships suggest to us that the rdAcbSh represents a basal forebrain transition area in the sense that it is invaded by lateral septal neurons or transitional neuronal forms sharing properties of both structures. The findings reported herein and how we have interpreted them are quite different from those described in another recently published report on the connections of the rdAcbSh (Thompson and Swanson, 2010).