The extended amygdala has been defined as a continuum of inter-related basal forebrain structures that includes the central amygdaloid nucleus (CEA), the sublenticular extended amygdala nuclei, the bed nucleus of the stria terminalis (BNST), and the shell of the NAcc [127
]. These nuclei share much in common and are involved in many motivated behaviors including reward-based operant conditioning and stress- or cue-induced reinstatement of drug seeking in animals [130
Among the extended amygdala structures, the BNST appears to be particularly important in motivated behaviors, including those driven by pharmacological agents [135
]. The BNST has been characterized as a cluster of approximately 12 interconnected nuclei [127
]. Whether BNST nuclei should be referred to a single unitary structure is a matter of debate. However, each of the neuronal clusters currently considered as BNST subnuclei are highly interconnected and have similar neuronal electrophysiological signatures, suggesting it may be appropriate to consider the BNST as a unit [140
]. These BNST nuclei are intricately interconnected with major components of the brain reward circuitry such as the VTA, the ventral striatum, and the hypothalamus [c.f. 144
and others from these authors].
The nuclei of the BNST have clear lateral/medial and ventral/dorsal gradients based on their function and anatomical connectivity. Lateral BNST nuclei preferentially connect with the lateral hypothalamus and lateral regions of the CEA, and medial BNST nuclei connect with medial CEA and medial hypothalamus [127
]. While the medial and lateral BNST networks are thought to influence endocrine function and motivated behaviors, respectively, anatomically specific lesions or pharmacological interventions will be required to clarify this issue.
There are also clear neurochemical distinctions between the ventral and dorsal BNST. Dopamine-containing terminals are restricted to BNST regions dorsal to the anterior commissure, whereas noradrenaline-containing terminals are preferentially, although not exclusively, located in the ventral BNST [148
]. As with the medial and lateral parts of the BNST, these anatomical distinctions may correspond to different functions: pharmacological manipulations of the dorsal BNST interfere with appetitive-motivated behaviors such as drug self-administration whereas noradrenergic antagonists in the ventral BNST reduces withdrawal-induced place aversion [135
The BNST contributes to coding the appetitive outcome of a given situation, responding to stimuli associated with both positive and negative affect. However, there is a relatively clear distinction between the types of stimuli that activate the BNST and those that activate other regions of the extended amygdala such as the CEA. Whereas the CEA is critical for discrete cue-induced conditioning, the BNST seems to play a special role in contextual conditioning [153
]. As such, the BNST is thought to contribute to a general `awareness' loosely linked to a particular context, rather than the prediction of specific outcomes by discrete cues [157
]. Consistent with this idea, the BNST, but not the CEA, receives a strong input from the VSub, which plays a key role in contextual conditioning [158
] (see Section 3).
One key feature of the BNST and other extended amygdala structures are their bidirectional anatomical connections with hypothalamic nuclei. Indeed, the extended amygdala is the main input to hypothalamic nuclei and, in return, several hypothalamic nuclei project back to regions of the extended amygdala [127
]. The extended amygdala seems to act as an important relay and integration center between cortical regions and hypothalamic nuclei [160
]. For example, the BNST projection to the paraventricular nucleus may be a pathway that allows contextual information (from the ventral subiculum) to influence motivated behavior. Of particular relevance to motivated behaviors is the relationship between the lateral hypothalamus and the lateral extended amygdala. Both the ventral BNST and the NAcc shell send projections to the lateral hypothalamus, which contains orexinergic neurons recently identified as important for drug-seeking behaviors [162
]. The lateral hypothalamus in turn projects back to the ventral BNST, though the functional significance of this reciprocal projection is not known (but see [163