Lateral hypothalamic GABAergic neurons encode alcohol memories.

Alonso-Lozares, I.; Wilbers, P.; Teijsse, S.; Asperl, L.; van der Neut, C.; Schetters, D.; Van Mourik, Y.; McDonald, A. J.; Heistek, T. S.; Mansvelder, H.; De Vries, T. J.; Marchant, N. J.

doi:10.1101/2023.11.16.567157

bioRxiv · 10.1101/2023.11.16.567157

Lateral hypothalamic GABAergic neurons encode alcohol memories.

Alonso-Lozares, I.·Wilbers, P.·Teijsse, S.·Asperl, L.·van der Neut, C.·Schetters, D.·Van Mourik, Y.·McDonald, A. J.·Heistek, T. S.·Mansvelder, H.·De Vries, T. J.·Marchant, N. J.

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Abstract

In alcohol use disorder the alcohol memories persist during abstinence, and exposure to stimuli associated with alcohol use can lead to relapse. This highlights the importance of investigating the neural substrates underlying not only relapse, but also encoding and expression of alcohol memories. GABAergic neurons in the Lateral Hypothalamus (LH- GABA) have been shown to be critical for food-cue memories and motivation, however the extent to which this role extends to alcohol-cue memories and motivations remains unexplored. In this study, we aimed to describe how alcohol related memories are encoded and expressed in LH GABAergic neurons. Our first step was to monitor LH-GABA calcium transients during acquisition, extinction, and reinstatement of an alcohol-cue memory using fiber photometry. We trained the rats on a Pavlovian conditioning task where one conditioned stimulus (CS+) predicted alcohol (20% EtOH) and another conditioned stimulus (CS-) had no outcome. We then extinguished this association through non-reinforced presentations of the CS+ and CS-, finally in two different groups we measured relapse under non-primed and alcohol primed induced reinstatement. Our results show that initially both cues caused increased LH-GABA activity, and after learning only the alcohol-cue increased LH-GABA activity. After extinction this activity decreases, and we found no differences in LH- GABA activity during reinstatement in either group. Next, inhibited LH-GABA neurons with optogenetics to show that activity of these neurons is necessary for the formation of an alcohol-cue associations. These findings suggest that LH-GABA might be involved in attentional processes modulated by learning.

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Alonso-Lozares, I., Wilbers, P., Teijsse, S., Asperl, L., van der Neut, C., Schetters, D., Van Mourik, Y., McDonald, A. J., Heistek, T. S., Mansvelder, H., De Vries, T. J., Marchant, N. J.. 2023-11-17. Lateral hypothalamic GABAergic neurons encode alcohol memories.. https://doi.org/10.1101/2023.11.16.567157

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