The amygdala and bed nucleus of the stria terminalis (BNST) are thought to subserve distinct functions, with the former mediating rapid fear responses to discrete sensory cues and the latter longer "anxiety-like" states in response to diffuse environmental contingencies. However, these structures are reciprocally connected and their projection sites overlap extensively. To shed light on the significance of BNST-amygdala connections, we compared the antidromic response latencies of BNST and central amygdala (CE) neurons to brain stem stimulation. Whereas the frequency distribution of latencies was unimodal in BNST neurons (approximately 10-ms mode), that of CE neurons was bimodal (approximately 10- and approximately 30-ms modes). However, after stria terminalis (ST) lesions, only short-latency antidromic responses were observed, suggesting that CE axons with long conduction times course through the ST. Compared with the direct route, the ST greatly lengthens the path of CE axons to the brain stem, an apparently disadvantageous arrangement. Because BNST and CE share major excitatory basolateral amygdala (BL) inputs, lengthening the path of CE axons might allow synchronization of BNST and CE impulses to brain stem when activated by BL. To test this, we applied electrical BL stimuli and compared orthodromic response latencies in CE and BNST neurons. The latency difference between CE and BNST neurons to BL stimuli approximated that seen between the antidromic responses of BNST cells and CE neurons with long conduction times. These results point to a hitherto unsuspected level of temporal coordination between the inputs and outputs of CE and BNST neurons, supporting the idea of shared functions.
"Heimer et al. have proposed that two parallel columns of extended amygdala neurons exist within the basal forebrain, a central extended amygdala that includes the central nucleus of the amygdala (Ce) and lateral portions of the BST (BSTL), and a medial extended amygdala including the medial nucleus of the amygdala (Me) and medial BST (see Figs. 1A, B). Neuroanatomical studies in rodents and nonhuman primates support the central extended amygdala concept by demonstrating that the Ce and BSTL are strongly connected and share many efferent targets (de Olmos and Heimer, 1999; Dong et al., 2001; Heimer and Van Hoesen, 2006; Nagy and Pare, 2008; see Fig. 1C). Additionally, although first noted by Johnson (1923), recent developmental data suggest that some of the constituent neurons of the Ce and BSTL are derived from similar embryological origins (Bupesh et al., 2011). "
[Show abstract][Hide abstract] ABSTRACT: Neuroanatomists posit that the central nucleus of the amygdala (Ce) and bed nucleus of the stria terminalis (BST) comprise two major nodes of a macrostructural forebrain entity termed the extended amygdala. The extended amygdala is thought to play a critical role in adaptive motivational behavior and is implicated in the pathophysiology of maladaptive fear and anxiety. Resting functional connectivity of the Ce was examined in 107 young anesthetized rhesus monkeys and 105 young humans using standard resting-state functional magnetic resonance imaging (fMRI) methods to assess temporal correlations across the brain. The data expand the neuroanatomical concept of the extended amygdala by finding, in both species, highly significant functional coupling between the Ce and the BST. These results support the use of in vivo functional imaging methods in nonhuman and human primates to probe the functional anatomy of major brain networks such as the extended amygdala.
"For instance, they both receive excitatory inputs from the basolateral amygdala (Krettek and Price, 1978ab; Sun and Cassell, 1993; Dong et al., 2001), the two are reciprocally connected, and their brainstem projections overlap extensively (Hopkins and Holstege, 1978; Price and Amaral, 1981; Dong et al., 2000; Dong and Swanson, 2004, 2006a–c). Moreover, a recent physiological study revealed that the conduction time of BNST and CEA neurons allows for a synchronization of their brainstem outputs (Nagy and Pare, 2008). "
[Show abstract][Hide abstract] ABSTRACT: While learning to fear stimuli that predict danger promotes survival, the inability to inhibit fear to inappropriate cues leads to a pernicious cycle of avoidance behaviors. Previous studies have revealed large inter-individual variations in fear responding with clinically anxious humans exhibiting a tendency to generalize learned fear to safe stimuli or situations. To shed light on the origin of these inter-individual variations, we subjected rats to a differential auditory fear conditioning paradigm in which one conditioned auditory stimulus (CS+) was paired to footshocks whereas a second (CS-) was not. We compared the behavior of rats that received pretraining excitotoxic lesions of the bed nucleus of the stria terminalis (BNST) to that of sham rats. Sham rats exhibit a continuum of anxious/fearful behaviors. At one end of the continuum were rats that displayed a poor ability to discriminate between the CS+ and CS-, high contextual freezing, and an anxiety-like trait in the elevated plus maze (EPM). At the other end were rats that display less fear generalization to the CS-, lower freezing to context, and a nonanxious trait in the EPM. Although BNST-lesioned rats acquired similarly high levels of conditioned fear to the CS+, they froze less than sham rats to the CS-. In fact, BNST-lesioned rats behaved like sham rats with high discriminative abilities in that they exhibited low contextual fear and a nonanxious phenotype in the EPM. Overall, this suggests that inter-individual variations in fear generalization and anxiety phenotype are determined by BNST influences on the amygdala and/or its targets.
The Journal of Neuroscience : The Official Journal of the Society for Neuroscience 09/2009; 29(33):10357-61. DOI:10.1523/JNEUROSCI.2119-09.2009 · 6.34 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The central nucleus of the amygdala (CEA) and lateral bed nucleus of stria terminalis (BST) are highly interconnected limbic forebrain regions that share similar connectivity with other brain regions that coordinate behavioral and physiological responses to internal and environmental stressors. Their similar connectivity is frequently referred to when describing the CEA and lateral BST together as a unified "central extended amygdala". However, the CEA and BST reportedly play distinct roles in behavioral and physiological responses associated with fear, anxiety, and social defeat, presumably due to differences in connectivity. To identify common and unique sources of input to the CEA and lateral BST, we performed dual retrograde tracing. Fluorogold and cholera toxin β were iontophoresed into the medial CEA (CEAm) and the anterior ventrolateral BST (BSTvl) of adult male rats. The anatomical distribution of tracer-labeled neurons was mapped throughout the brain. Regions with overlapping populations of CEAm- and BSTvl-projecting neurons were further examined for the presence of double-labeled neurons. Although most regions with input to the mCEA also projected to the BSTvl, and vice versa, cortical and sensory system-related regions projected more robustly to the CEAm, while motor system-related regions primarily innervated the BSTvl. The incidence of double-labeled neurons with collateralized axonal inputs to the CEAm and BSTvl was relatively small (~2 to 13%) and varied across regions, suggesting regional differences in the degree of coordinated CEAm and BSTvl input. The demonstrated similarities and differences in inputs to CEAm and BSTvl provide new anatomical insights into the functional organization of these limbic forebrain regions.
Brain Structure and Function 02/2012; 218(1). DOI:10.1007/s00429-012-0393-6 · 5.62 Impact Factor
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