Abstract
The central nucleus of the amygdala (Ce) has connections with selective areas in the entire neuraxis. Through these projections, it receives a considerable amount of sensory information and is in the position to modulate somatic and autonomic responses to emotionally relevant stimuli. Its striatal-pallidal like organization may also contribute to the regulation of the "smoothness" and "tonus" of these emotional responses. Here, we give an overview of the connections of the Ce, including peptidergic connections, and present the organization of the projections of the Ce to four selected brain areas: the substantia innominata (SI), paraventricular nucleus of the hypothalamus (NPV), pontine nuclei in reticular formation (PNR) and dorsal motor nucleus of vagus/nucleus of the solitary tract (DMX/NST) complex. All four regions are involved in the modulation of distinct aspects of the emotional responses in the fear-sensitized acoustic startle reflex paradigm, in which they modulate arousal and attentional mechanisms, endocrine and cardiovascular stress responses, the startle response and parasympathetic functions. The contribution of subnuclei of the Ce to specific projections and their topography, as well as the occurrence of neurons that project to more than one target, are determined using the retrograde tracers Fluorogold (FG) and True Blue (TB). In addition, the proportion of neurons in the subnuclei of the Ce projecting to these areas is quantified. The timeline of various types of fear responses (fear-sensitized acoustic startle response, heart rate, blood pressure and body temperature) studied in a startle chamber and using telemetry electrodes are presented. The heaviest Ce projections are observed after injection into the DMX/NST, and the weakest projections after injections into the NPV. For all targets, the majority of Ce projection neurons (>60%) is located in the medial central nucleus (CeM). The lateral central nucleus (CeL) contributes to about 20% of the projections to the SI, about 10% to the DMX/NST, about 5% to the NPV and virtually none to the PNR. The contribution of the capsular part of the central nucleus (ClC) to projections is, in general, less than 5%. In contrast to the more dispersed distribution of neurons projecting to the SI, the neurons innervating the NPV, DMX/NST and PNR show a rather complementary arrangement, at least in the rostral and dorsal/dorsolateral parts of the CeM. The injection of both tracers in various combinations into the targets reveals in all cases double-labeled neurons, but in small numbers. The modality-specific input to subnuclei of the Ce and the organization of projections to the different downstream regions indicates that the Ce is more than a mere output relais of the amygdala. The differential organization of projections originating in the subnuclei of the Ce may be important for an independent treatment of various components of fear-, anxiety- and stress-related responses, because the brain nuclei examined are mainly targeted by separate populations of neurons within the Ce that may be recruited independently to regulate different aspects of emotional behavior.