Enhanced Retrieval of Taste Associative Memory by Chemogenetic Activation of Locus Coeruleus Norepinephrine Neurons

Abstract

The ability of animals to retrieve memories stored in response to the environment is essential for behavioral adaptation. Norepinephrine (NE)-containing neurons in the brain play a key role in the modulation of synaptic plasticity underlying various processes of memory formation. However, the role of the central NE system in memory retrieval remains unclear. Here, we developed a novel chemogenetic activation strategy exploiting insect olfactory ionotropic receptors (IRs), termed "IRmediated neuronal activation," and used it for selective stimulation of NE neurons in the locus coeruleus (LC). Drosophila melanogaster IR84a and IR8a subunits were expressed in LC NE neurons in transgenic mice. Application of phenylacetic acid (a specific ligand for the IR84a/IR8a complex) at appropriate doses induced excitatory responses of NE neurons expressing the receptors in both slice preparations and in vivo electrophysiological conditions, resulting in a marked increase of NE release in the LC nerve terminal regions (male and female). Ligand-induced activation of LC NE neurons enhanced the retrieval process of conditioned taste aversion without affecting taste sensitivity, general arousal state, and locomotor activity. This enhancing effect on taste memory retrieval was mediated, in part, through a 1 -and b-adrenergic receptors in the basolateral nucleus of the amygdala (BLA; male). Pharmacological inhibition of LC NE neurons confirmed the facilitative role of these neurons in memory retrieval via adrenergic receptors in the BLA (male). Our findings indicate that the LC NE system, through projections to the BLA, controls the retrieval process of taste associative memory.

Molecular reconstruction of recurrent evolutionary switching in olfactory receptor specificity

“…Future expansion of the odor profiling of these species’ receptors will be essential to understand the pressures in the natural world that have selected for olfactory receptor proteins with new chemical recognition properties. Such knowledge, together with mechanistic insight into ligand/receptor interactions, may be useful to reengineer the ligand-binding specificities of receptors to create, for example, chemogenetic tools ( Fukabori et al, 2020 ) or design pharmacological manipulators to control the olfactory-guided behaviors of pest insects.…”

The locus coeruleus contributes to the anorectic, nausea, and autonomic physiological effects of glucagon-like peptide-1

“…While our data support delayed gastric emptying and nausea contributing to the anorexia observed following LC GLP-1R activation, other factors may also be at play. Future work will examine the contribution of LC GLP-1Rs to LC NE signaling-induced changes in stress, anxiety, and aversion (71)(72)(73) in addition to arousal (74), foraging behavior (75), and sensory encoding that includes taste perception (76,77); all of which may contribute to the observed food intake reduction following GLP-1R activation in the LC. Given that hindbrain PPG neurons are activated by stress including gastric distention and visceral malaise (50), it is possible that the LC mediates a range of responses to homeostatic challenge.…”

The role of hippocampus in memory reactivation: an implication for a therapeutic target against opioid use disorder

“…In addition to the hippocampus, the amygdala is another important region in memory encoding and retrieval [97,[128][129][130]. Both the amygdala and the hippocampus are directly innervated by the LC [131,132].…”