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Highlights • IL-1β (1 µg, i.p.) induced sickness-like behavior in adult male Sprague–Dawley rats. • It increased the firing rate in the BLA complex acutely with a change in firing pattern. • The effect was more prominent in the basal nucleus of the BLA complex. • LPS (250 μg/kg, i.p.) increased BLA firing rate acutely and persistently. • Immunogen challenge increased BLA firing rate before serum IL-1β reached its peak. Abstract Peripheral inflammation often causes changes in mood and emergence of depressive behavior, and is characterized by a group of physical manifestations including lethargy, malaise, listlessness, decreased appetite, anhedonia, and fever. These behavioral changes are induced at the molecular level by pro-inflammatory cytokines like interleukin (IL)-1β, IL-6 and TNF-α. The basolateral amygdala (BLA) is a key brain region involved in mood and may mediate some of the behavioral effects of inflammation. However, it is unknown whether peripheral inflammatory state affects the activity of BLA neurons. To test this, adult male Sprague–Dawley rats were treated with IL-1β (1 μg, intraperitoneal (i.p.)), and behavioral and electrophysiological measures were obtained. IL-1β reduced locomotion in the open-field test and also reduced home-cage mobility, consistent with features of sickness-like behavior. Using in vivo single-unit extracellular electrophysiological recordings from anesthetized rats, we found that spontaneous BLA neuronal firing was acutely (<30 min) increased after IL-1β, followed by a return to baseline level, particularly in the basal nucleus of the BLA complex. To verify and expand on effects of peripheral inflammation, we tested whether another, long-lasting inflammagen also changes BLA neuronal firing. Lipopolysaccharide (250 μg/kg, i.p.) increased BLA firing rate acutely (<30 min) and persistently. The findings demonstrate a rapid effect of peripheral inflammation on BLA activity and suggest a link between BLA neuronal firing and triggering of behavioral consequences of peripheral inflammation. These findings are a first step toward understanding the neuronal basis of depressive behavior caused by acute peripheral inflammation. [ABSTRACT FROM AUTHOR]

Background: Chronic stress is a major health concern, often leading to depression, anxiety, or when severe enough, posttraumatic stress disorder. While many studies demonstrate that the amygdala is hyperresponsive in patients with these disorders, the cellular neurophysiological effects of chronic stress on the systems that underlie psychiatric disorders, such as the amygdala, are relatively unknown. Methods: In this study, we examined the effects of chronic stress on the activity and excitability of amygdala neurons in vivo in rats. We used in vivo intracellular recordings from single neurons of the lateral amygdala (LAT) to measure neuronal properties and determine the cellular mechanism for the effects of chronic stress on LAT neurons. Results: We found a mechanism for the effects of chronic stress on amygdala activity, specifically that chronic stress increased excitability of LAT pyramidal neurons recorded in vivo. This hyperexcitability was caused by a reduction of a regulatory influence during action potential firing, facilitating LAT neuronal activity. The effects of stress on excitability were occluded by agents that block calcium-activated potassium channels and reversed by pharmacological enhancement of calcium-activated potassium channels. Conclusions: These data demonstrate a specific channelopathy that occurs in the amygdala after chronic stress. This enhanced excitability of amygdala neurons after chronic stress may explain the observed hyperresponsiveness of the amygdala in patients with posttraumatic stress disorder and may facilitate the emergence of depression or anxiety in other patients. [Copyright &y& Elsevier]

Background: The basolateral complex (BLA) and the central nucleus of the amygdala (CeA) are believed to mediate the expression of affective responses. After affective learning, conditioned stimulus–related information is thought to be conveyed from the BLA to the CeA; the medial CeA (Cem), in turn, projects to hypothalamic and brainstem structures involved with induction of affective responses. Although the conditioned stimulus and unconditioned stimulus both evoke affective responses, the precise response often differs. It is unknown whether this difference is represented by distinct activity patterns of single Cem neurons. Furthermore, the nature of the interaction between the BLA and Cem is unknown. Methods: Using in vivo extracellular and intracellular recordings, we examined how the BLA affects the Cem and compared this with effects induced by footshock (unconditioned stimulus) in the same neurons. Results: Our results demonstrate that, contrary to conventional views, BLA stimulation primarily inhibits Cem neurons by a polysynaptic circuit, and show that single Cem neurons respond to both BLA input and footshock in an opposite manner. Conclusions: These results demonstrate the predominantly inhibitory nature of the BLA–Cem interaction. These data further demonstrate the distinct cellular events that might lead to differential modulation of conditioned and unconditioned affective responses. [Copyright &y& Elsevier]

Background: Recent studies suggest that long-term exposure to stress can sensitize animals to subsequent novel or acute stressors. Stressors affect amygdala activity, and the prefrontal cortex has been implicated in the regulation of responses to stress. Little is known, however, about how the physiology of amygdala neurons is altered by chronic stressors or the role of the prefrontal cortex in these changes. Methods: We used in vivo extracellular recordings from neurons in the rat central and basolateral amygdala nuclei to examine the effects of chronic stress on the basal firing and responses of amygdala neurons to a novel stressor. Additionally, prefrontal cortical afferents were severed to examine its role in the modulation of the response to stressors. Results: Chronic exposure to cold enhanced the sensitivity of central amygdala neurons to footshock. A portion of this may be due to enhanced basolateral amygdala output. Furthermore, prefrontal cortical regulation of this response is weakened by chronic stress. Conclusions: The physiology of the amygdala is altered by chronic stress. Furthermore, the prefrontal cortical regulation of these responses may be weakened after chronic stress. This is a potential biological substrate for abnormal affect upon chronic stress and its effect on affective disorders. [Copyright &y& Elsevier]

The basolateral amygdala (BLA) is a component of a system that drives and modulates affective behavior. Some forms of affective behavior are regulated by the prefrontal cortex (PFC) and enhanced by dopamine (DA). By using intracellular and extracellular electrophysiological techniques in anesthetized rats, our studies attempt to uncover cellular mechanisms that allow for regulation of affect by PFC-induced inhibition of BLA output and plasticity, as well as mechanisms by which DA enhances affective behavior via modulation of BLA neuronal excitability, afferent input and plasticity. We have found that stimulation of medial PFC (mPFC) results in a profound inhibition of BLA output, manifest as a suppression of spontaneous, intracellular current-driven or sensory cortical afferent-driven spike firing of BLA projection neurons. This inhibition is mediated by excitation of GABAergic interneurons of the BLA. Activation of DA receptors attenuates this inhibitory action of the mPFC, while enhancing other (i.e., sensory-related) inputs by increases in postsynaptic excitability of BLA projection neurons. Furthermore, Pavlovian conditioning procedures that pair an odor with a footshock result in enhanced odor-evoked postsynaptic potentials. This plasticity of odor-evoked responses is blocked by antagonism of DA receptors and by stimulation of mPFC. Our data indicate that the mPFC exerts regulatory control over BLA via suppression of spontaneous and sensory-driven activity, as well as BLA plasticity. Activation of DA receptors suppresses the inhibitory influence of the mPFC, allowing sensory-driven BLA activity and plasticity. Functionally, in the presence of high DA levels, which suppresses mPFC-evoked inhibition, one source of affective control will be dampened. Furthermore, sensory-related inputs will be further enhanced by the increased excitability of BLA neurons. This situation is expected to maximize affective responses to sensory stimuli, as well as plasticity. [Copyright &y& Elsevier]

• Development is characterized by changes in fear learning and social behavior. • Adolescence is a period of heightened sensitivity to stressors. • Behavioral changes during development coincide with cortico-amygdala maturation. • Cortico-amygdala maturation may underlie stressor sensitivity that impacts behavior. Stress can negatively impact brain function and behaviors across the lifespan. However, stressors during adolescence have particularly harmful effects on brain maturation, and on fear and social behaviors that extend beyond adolescence. Throughout development, social behaviors are refined and the ability to suppress fear increases, both of which are dependent on amygdala activity. We review rodent literature focusing on developmental changes in social and fear behaviors, cortico-amygdala circuits underlying these changes, and how this circuitry is altered by stress. We first describe changes in fear and social behaviors from adolescence to adulthood and parallel developmental changes in cortico-amygdala circuitry. We propose a framework in which maturation of cortical inputs to the amygdala promote changes in social drive and fear regulation, and the particularly damaging effects of stress during adolescence may occur through lasting changes in this circuit. This framework may explain why anxiety and social pathologies commonly co-occur, adolescents are especially vulnerable to stressors impacting social and fear behaviors, and predisposed towards psychiatric disorders related to abnormal cortico-amygdala circuits. [ABSTRACT FROM AUTHOR]

Responds to comments on a study suggesting that associative synaptic changes take place in neurons of the amygdala during fear conditioning, and that these changes require dopamine-mediated modulation. Role of dopamine beyond the hedonic appreciation of reward; Plasticity under anesthesia; Learning under the influence of anesthesia.