Regulation of the Fear Network by Mediators of Stress: Norepinephrine Alters the Balance between Cortical and Subcortical Afferent Excitation of the Lateral Amygdala

Abstract

Pavlovian auditory fear conditioning involves the integration of information about an acoustic conditioned stimulus (CS) and an aversive unconditioned stimulus in the lateral nucleus of the amygdala (LA). The auditory CS reaches the LA subcortically via a direct connection from the auditory thalamus and also from the auditory association cortex itself. How neural modulators, especially those activated during stress, such as norepinephrine (NE), regulate synaptic transmission and plasticity in this network is poorly understood. Here we show that NE inhibits synaptic transmission in both the subcortical and cortical input pathway but that sensory processing is biased toward the subcortical pathway. In addition binding of NE to β-adrenergic receptors further dissociates sensory processing in the LA. These findings suggest a network mechanism that shifts sensory balance toward the faster but more primitive subcortical input.

Mechanisms contributing to the induction and storage of Pavlovian fear memories in the lateral amygdala

“…The simulated LAd network included conductance-based models of 800 principal cells and 200 interneurons that reproduced the electroresponsive properties of these cell types, as observed experimentally ( Fig. 1; for review, see Sah et al 2003), and neuromodulatory inputs from brainstem dopaminergic and noradrenergic neurons (Johnson et al 2011). In addition, based on previous in vitro experiments (Samson and Paré 2006), the model network integrated spatially differentiated patterns of excitatory and inhibitory connections within LA (Fig.…”

Synaptic competition in the lateral amygdala and the stimulus specificity of conditioned fear: a biophysical modeling study

“…1A). As detailed below, the LAd network also featured neuromodulatory inputs from brainstem dopaminergic and noradrenergic neurons (Johnson et al 2011), as well as probabilistic gradients of inhibitory and excitatory connections (Fig. 2, Kim et al 2013a) within LAd.…”

The gray matter alterations in major depressive disorder and panic disorder: Putative differences in the pathogenesis

“…(Arnone et al, 2012;Bora et al, 2012;Wise et al, 2014) Therefore we hypothesized that MDD patients would have frontal-limbic GMV deficits. For the PD, fear circuit will play an important role in the pathophysiology, including frontal regions (de Carvalho et al, 2010;Gorman et al, 2000;Johnson et al, 2011). Several frontal-related GMV alterations in PD patients would suggest the alterations in the top-down regulation mechanism (Asami et al, 2009;Lai et al, 2010;Lai and Wu, 2012;Protopopescu et al, 2006;Roppongi et al, 2010;Sobanski et al, 2010;van Tol et al, 2010;Yoo et al, 2005).…”