6 research outputs found
An interaction between locus coeruleus activation modes and heterogeneous adrenoceptor expression in the basolateral amygdala for valence signaling
No full textThe locus coeruleus (LC) is a neuromodulatory brainstem nucleus which signals arousal via the release of norepinephrine (NE) throughout the central nervous system. Norepinephrine facilitates adaptive behavioural responding, perception, and learning and memory via enhancing the signal-to-noise ratio at downstream structures. The LC has recently been suggested to be involved in positive and negative valence signaling via two distinct activation modes, phasic and tonic. This effect has been shown to depend on adrenoceptor engagement in the basolateral amygdala (BLA). Here, we sought to determine whether phasic and tonic modes of LC activation differentially engage functionally distinct subpopulations of the BLA and whether naturally-produced valence recruits the same circuitry. Finally, we investigated the adrenoceptor profile of these subpopulations, as our valence effects may depend on their unique adrenoceptor expressions. Phasic and tonic LC photostimulation preferentially recruited nucleus accumbens (NAc)- and central amygdala (CeA)-projecting subpopulations of the BLA in the presence of an odor, respectively. Natural reward and aversive learning showed patterns of BLA activation similar to that of phasic and tonic LC photostimulation, respectively. Immunohistochemistry revealed differences in adrenoceptor expression across BLA subpopulations. These findings offer a mechanism underlying the differential valence effects of phasic and tonic LC activation.Includes bibliographical references (pages 49-66
Phasic and Tonic Locus Coeruleus Stimulation Associated Valence Learning Engages Distinct Adrenoceptors in the Rat Basolateral Amygdala
No full textReward exploitation and aversion are mediated in part by the locus coeruleus (LC), a brainstem structure significantly involved in learning and memory via the release of norepinephrine. Different LC firing patterns are associated with different functions. Previously, we have shown that high tonic and phasic LC activation signal negative and positive valence, respectively, via basolateral amygdala (BLA) circuitry. Tonic LC activation is associated preferentially with BLA-central amygdala (CeA) activation, while phasic LC stimulation preferentially recruits the BLA-nucleus accumbens (NAc) pathway. Here, we ask if phasic and tonic LC activation-associated valence learning requires different adrenoceptors in the BLA, in comparison with the odor valence learning induced by natural reward and aversive conditioning. Using optogenetic activation of the LC and local drug infusions in the BLA, we show that phasic LC activation-induced positive odor valence learning is dependent on both α(1) and β-adrenoceptors, whereas tonic LC activation induced-negative odor valence learning depends on β-adrenoceptors only. In parallel, both α(1) and β-adrenoceptors were required in the odor valence learning induced by reward while aversive conditioning was dependent on β-adrenoceptors. Phasic stimulation and reward conditioning likewise activated more NAc-projectors of the BLA, in comparison to tonic and aversive conditioning. There was a higher proportion of α(1)(+) cells in the NAc-projectors compared to CeA-projectors in the BLA. Together, these results provide insight into the mechanisms underlying the effects of tonic and phasic activation of the LC, and more generally, negative and positive valence signaling
The Basolateral Amygdala: The Core of a Network for Threat Conditioning, Extinction, and Second-Order Threat Conditioning
No full textThreat conditioning, extinction, and second-order threat conditioning studied in animal models provide insight into the brain-based mechanisms of fear- and anxiety-related disorders and their treatment. Much attention has been paid to the role of the basolateral amygdala (BLA) in such processes, an overview of which is presented in this review. More recent evidence suggests that the BLA serves as the core of a greater network of structures in these forms of learning, including associative and sensory cortices. The BLA is importantly regulated by hippocampal and prefrontal inputs, as well as by the catecholaminergic neuromodulators, norepinephrine and dopamine, that may provide important prediction-error or learning signals for these forms of learning. The sensory cortices may be required for the long-term storage of threat memories. As such, future research may further investigate the potential of the sensory cortices for the long-term storage of extinction and second-order conditioning memories
Locus Coeruleus Activation Patterns Differentially Modulate Odor Discrimination Learning and Odor Valence in Rats
No full textThe locus coeruleus (LC) produces phasic and tonic firing patterns that are theorized to have distinct functional consequences. However, how different firing modes affect learning and valence encoding of sensory information are unknown. Here, we show bilateral optogenetic activation of rat LC neurons using 10-Hz phasic trains of either 300 ms or 10 s accelerated acquisition of a similar odor discrimination. Similar odor discrimination learning was impaired by noradrenergic blockade in the piriform cortex (PC). However, 10-Hz phasic light-mediated learning facilitation was prevented by a dopaminergic antagonist in the PC, or by ventral tegmental area (VTA) silencing with lidocaine, suggesting a LC–VTA–PC dopamine circuitry involvement. Ten-hertz tonic stimulation did not alter odor discrimination acquisition, and was ineffective in activating VTA DA neurons. For valence encoding, tonic stimulation at 25 Hz induced conditioned odor aversion, whereas 10-Hz phasic stimulations produced an odor preference. Both conditionings were prevented by noradrenergic blockade in the basolateral amygdala (BLA). Cholera Toxin B retro-labeling showed larger engagement of nucleus accumbens-projecting neurons in the BLA with 10-Hz phasic activation, and larger engagement of central amygdala projecting cells with 25-Hz tonic light. These outcomes argue that the LC activation patterns differentially influence both target networks and behavior.Memorial University Open Access Author's Fun
Second-order threat conditioning in the amygdala-posterior piriform cortex network
No full textAbstract Fear, while crucial for survival, is a component of a myriad of psychiatric illnesses in its extreme. Persistent fear memories can form through processes such as second-order conditioning (SOC), during which a second-order conditioned stimulus (CS2) acquires significance by associating with a first-order conditioned stimulus (CS1). The neural circuitry underlying SOC, particularly the roles of sensory cortices, remains poorly understood. Here we explore the mechanisms of olfactory SOC in rats, focusing on the basolateral amygdala (BLA) and posterior piriform cortex (pPC). Our results demonstrate that NMDAR-dependent plasticity in both regions is essential for SOC. The BLA mediates the CS2-CS1 association, while the pPC, receiving inputs from the locus coeruleus and BLA, is critical for memory acquisition and retrieval. Single-nucleus multiomics analysis of Fos + ensembles in both regions reveals distinct yet overlapping gene activation profiles in excitatory neurons, accompanied by global chromatin remodeling. These findings highlight the specific yet coordinated roles of these structures in supporting learning and memory
Criminal responsibility for intrusions on the rights of innocent persons: the limits of self-defence, necessity and duress
No full textThis thesis is an exploratory study of the boundaries of English and Welsh criminal law where the legally protected personal and proprietary interests of innocent persons are intentionally infringed by another. Despite fulfilling the definitional elements of a criminal offence, there may be circumstances in which the law is prepared to exculpate the actor even where the interests of an innocent person are set back by the conduct. The justifications and excuses to be considered fall predominantly within the province of self-defence, necessity and duress and the correspondence between these respective domains is addressed. The aim is to explore the extent to which the criminal law in a liberal society negates criminal liability for deliberate intrusions on the rights of innocent persons by defining the precise scope of the relevant defences. The innocent persons to be considered fall into three main categories. First, the criminal responsibility of an actor who sets back the interests of an innocent incompetent person in their best interests will be addressed. Next, the liability of a defendant who infringes the rights of an innocent person who poses a threat, unjust or incidental, to the interests of the defendant or another will be analysed. Finally, the criminal responsibility of an actor who violates the rights of an innocent non-threatening bystander in order to stave off a threat to their own interests will be considered. It is argued that in English law the scope of criminal liability for intentional acts which set back the interests of an innocent person is ill-defined. An attempt is made to provide a more consistent philosophical and practical approach to the limits of criminal responsibility in this challenging area of law
