J Neurosci. 2020 Sep 29;JN-RM-1720-20. doi: 10.1523/JNEUROSCI.1720-20.2020. Online ahead of print.
Enhanced Retrieval of Taste Associative Memory by Chemogenetic Activation of Locus Coeruleus Norepinephrine Neurons
Ryoji Fukabori 1, Yoshio Iguchi 1, Shigeki Kato 1, Kazumi Takahashi 2, Satoshi Eifuku 2, Shingo Tsuji 3, Akihiro Hazama 3, Motokazu Uchigashima 4, Masahiko Watanabe 4, Hiroshi Mizuma 5, Yilong Cui 6, Hirotaka Onoe 7, Keigo Hikishima 8, Yasunobu Yasoshima 9, Makoto Osanai 10, Ryo Inagaki 10, Kohji Fukunaga 11, Takuma Nishijo 12, Toshihiko Momiyama 12, Richard Benton 13, Kazuto Kobayashi 14
Animals’ ability 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 “IR-mediated neuronal activation” (IRNA), 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 α1– and β-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.
Norepinephrine (NE)-containing neurons in the brain play a key role in the modulation of synaptic plasticity underlying various processes of memory formation, but the role of the NE system in memory retrieval remains unclear. We developed a chemogenetic activation system based upon insect olfactory Ionotropic Receptors and used it for selective stimulation of NE neurons in the locus coeruleus (LC) in transgenic mice. Ligand-induced activation of LC NE neurons enhanced the retrieval of conditioned taste aversion, which was mediated, in part, through adrenoceptors in the basolateral amygdala. Pharmacological blockade of LC activity confirmed the facilitative role of these neurons in memory retrieval. Our findings indicate that the LC-amygdalar pathway plays an important role in the recall of taste associative memory.
- PMID: 32994339
- DOI: 10.1523/JNEUROSCI.1720-20.2020