Untitled

Stress-Induced Pathophysiology 247tently excited by a peptide, corticotrophin releasing factor (CRF), that has alsobeen associated with stressors (Jedema & Grace, 2003b; Valentino & Foote, 1988).When an animal is exposed to chronic stress, the levels of CRF in the locus coeruleuswill increase (Valentino & Foote, 1986). Therefore, it is believed that chronicstress will sensitize the response of the locus coeruleus both directly by changesin membrane characteristics of the neurons (Jedema & Grace, 2003b), as well asvia increasing the levels of CRF in this region.One area that supplies CRF input into the locus coeruleus is the central nucleusof the amygdala. This region comprises primarily gama aminobutyric acid (GABA)containing neurons that also utilize CRF as a cotransmitter. Our recent data (Rosenkranzet al., 2006) show that, recorded in vivo, the neurons of the central nucleusof the amygdala exhibit bistable firing patterns similar to that described for thenucleus accumbens (O’Donnell & Grace, 1995), in which the neurons alternatefrom a hyperpolarized, inactive state and a depolarized state during which theyfire spontaneously and can be driven by excitatory afferents. Such bistable statesin the accumbens and the cortex are thought to provide a gating of informationflow through these regions (O’Donnell & Grace, 1995). Despite the fact that theprimary transmitter emanating from the central amygdala output region has longbeen considered to be the inhibitory GABAergic circuitry, our recent data (Ramsooksinghet al., 2004) show that stimulation of this region provides an excitatorydrive onto the locus coeruleus, particularly when stimulated in bursts. Moreover,a CRF antagonist, revealing an underlying GABAergic component, can block thisexcitation.The central nucleus of the amygdala receives a complex array of afferent inputs.As mentioned above, one of the primary inputs is via the glutamatergic pyramidalneurons of the basal and lateral nuclear complex of the amygdala (Kretteck& Price, 1978). However, studies that have tried to evaluate the net effect of activatingthis pathway are controversial. This is because the output neurons in thebasal/lateral amygdala region project both directly to the central amygdala, as wellas activating a group of GABAergic interneurons lying within the region knownas the intercalated cell masses. This region provides a potent GABAergic inhibitionof the central amygdala. In vivo extracellular studies have shown that stimulationof the basal/lateral amygdala tends to excite the central amygdala (Quirket al., 2003). However, the central amygdala tends to show very low levels of spontaneousactivity, making an inhibitory input difficult to detect. In contrast, whenexamined using in vivo intracellular recordings, we have demonstrated that basaland lateral amygdala activation produces primarily an inhibition of centralamygdala output via activation of the intercalated cell masses (Rosenkranz et al.,2006). This finding is actually more consistent with the behavioral data concerningbasal and lateral amygdala interactions than is the excitatory interaction proposedto occur as derived from extracellular recording studies (Quirk et al., 2003).The interaction of these regions is central to understanding how the prefrontal