Extended Amygdala
Determining the circuitry operant in the brain responsible for development of fear and anxiety is key to developing suitable treatments for the wide range of human anxiety disorders. The extended amygdala is a macrostructure in the forebrain that includes three key players in fear and anxiety-like behaviors: the basolateral nucleus of the amygdala(BLA), central nucleus of the amygdala (CeA), and bed nucleus of the stria terminalis (BNST). The BLA sends excitatory projections to both CeA and BNST, which in turn project to brainstem structures involved in the expression of fearful behaviors.The BNST is an important relay for multiple cortical and subcortical regions and sends diverse projections to many brain areas that are involved in fear/anxiety related
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responses (Hopkins and Holstege 1978; Sofroniew 1983; Veening et al. 1984; Holstege et al. 1985; Dong et al. 2000, 2001b; Dong and Swanson 2003, 2004, 2006a,b, c) such as central Amygdala (CeA)(Alheid and Heimer 1988; de Olmos and Heimer 1999) and brainstem nuclei. It has contrasting connections with fear effector neurons and has been implicated in behaviors related to fear related disorders (Bota et al., 2012). BNST lesions result in disruption of freezing responses to contextual fear (Sullivan et al. 2004).Its activity exerts a tonic inhibitory influence on fear output networks and infusions of muscimol, a GABA-A agonist enhances the fear-potentiated startle (Meloni et al. 2006). Intra-BNST infusions of calcitonin gene-related peptide (CGRP) increase startle response along with enhanced c-Fos expression in CeA (Campeau et al. 1997; Sink et al. 2011). CGRP potentiates GABAergic inhibition in neurons of BNST-AL/STLP (Gungor and Pare 2012), the BNST region receiving CGRP inputs from the parabrachial nucleus (Gustafson and Greengard 1990; Dobolyi et al. 2005). Since most BNST neurons are GABAergic (Esclapez et al. 1993; Poulin et al. 2009), these results suggest the startle enhancement produced by intra-BNST infusions of CGRP is due to the inhibition of BNST-AL neurons resulting in the disinhibition of CeA.
Recent studies in the extended amygdala show a functional dissociation in the role of the central amygdala (CeA) and the bed nucleus of the stria terminalis (BNST) in the expression fear.
While CeA has been shown to be involved in the expression of both cued and contextual fear the BNST has been shown to be involved in the expression of contextual fear only. The basis for this difference has been attributed to regional differences in the activity of BNST-AL and -AM in relation to learned fear, raising the possibility that they exert opposite influences on fear output networks. The molecular mechanism underlying the differential activity in the subdivisions of BNST is unclear.The present study was undertaken to look at the molecular mechanism which control the differential activity of these sub-regions of BNST, during fear learning and its extinction. In the present study we worked towards the hypothesis that the differential activation of the neuronal subpopulations in the BNST and Amygdala is due to different expression patterns of memory related genes such as CREB in the neurons in these sub-regions and that this differential expression may be under the control of epigenetics especially Histone
acetylation.
responses (Hopkins and Holstege 1978; Sofroniew 1983; Veening et al. 1984; Holstege et al. 1985; Dong et al. 2000, 2001b; Dong and Swanson 2003, 2004, 2006a,b, c) such as central Amygdala (CeA)(Alheid and Heimer 1988; de Olmos and Heimer 1999) and brainstem nuclei. It has contrasting connections with fear effector neurons and has been implicated in behaviors related to fear related disorders (Bota et al., 2012). BNST lesions result in disruption of freezing responses to contextual fear (Sullivan et al. 2004).Its activity exerts a tonic inhibitory influence on fear output networks and infusions of muscimol, a GABA-A agonist enhances the fear-potentiated startle (Meloni et al. 2006). Intra-BNST infusions of calcitonin gene-related peptide (CGRP) increase startle response along with enhanced c-Fos expression in CeA (Campeau et al. 1997; Sink et al. 2011). CGRP potentiates GABAergic inhibition in neurons of BNST-AL/STLP (Gungor and Pare 2012), the BNST region receiving CGRP inputs from the parabrachial nucleus (Gustafson and Greengard 1990; Dobolyi et al. 2005). Since most BNST neurons are GABAergic (Esclapez et al. 1993; Poulin et al. 2009), these results suggest the startle enhancement produced by intra-BNST infusions of CGRP is due to the inhibition of BNST-AL neurons resulting in the disinhibition of CeA.
Recent studies in the extended amygdala show a functional dissociation in the role of the central amygdala (CeA) and the bed nucleus of the stria terminalis (BNST) in the expression fear.
While CeA has been shown to be involved in the expression of both cued and contextual fear the BNST has been shown to be involved in the expression of contextual fear only. The basis for this difference has been attributed to regional differences in the activity of BNST-AL and -AM in relation to learned fear, raising the possibility that they exert opposite influences on fear output networks. The molecular mechanism underlying the differential activity in the subdivisions of BNST is unclear.The present study was undertaken to look at the molecular mechanism which control the differential activity of these sub-regions of BNST, during fear learning and its extinction. In the present study we worked towards the hypothesis that the differential activation of the neuronal subpopulations in the BNST and Amygdala is due to different expression patterns of memory related genes such as CREB in the neurons in these sub-regions and that this differential expression may be under the control of epigenetics especially Histone
acetylation.