Time matters: Integration of time information into memory processes
Final Report Abstract
In 2014 John O´Keefe, May-Britt Moser and Edvard I. Moser were honoured with the Nobel Prize in Physiology and Medicine for their work on cells that constitute a positioning system in the brain. Special cells, place and grid cells, enable the brain to orientate within the environment, allowing us to know where we are, how to navigate from one place to another and to form and express spatial memories. For animals both spatial navigation and spatial memories are essential to enhance fitness and survival based on the timely relocation of food sources and mating partners and the avoidance of predators which often establish typical hunting routes. But how are the circadian clock and memory circuits connected? Overall, the proposed project aimed at a deeper understanding of the neuronal circuits and mechanisms of how time of day is integrated into memories, which is equally important in a variety of organisms from insects to humans. Since dissociation between the output of the circadian clock and external environmental stimuli triggers cognitive dysfunction in humans, it is important to close this knowledge gap. The present research set out to identify output signals of the circadian clock modulating memory performance. For this, the research program focussed on two central work packages: (i) First, we established a heat maze arena resembling the Morris Water maze allowing to study spatial learning in different species. We could provide evidence that flies, ants and bees can avoid harmful temperatures by associating a cold spot position to surrounding landmarks. In flies, memory performance was dependent on the time of day at which the experiments where performed. (ii) The main part of the intended project focussed on circadian modulation of learning in Drosophila and circuit analysis of the underlying structures. Here, we identified diuretic hormone 31 (DH31) as a downstream target of pigment-dispersing factor (PDF), a neurotransmitter released from central clock neurons. DH31 is released from dorsal clock neurons (DN1ps) and signals to the mushroom body, the main memory centre in Drosophila. DH31 to mushroom body signalling appeared to be predominantly required in the flies´ subjective evening suggesting that different clock neurons are important to fine-tune stable memory performance throughout 24h. Furthermore, towards the end, the research programme also included a focus on time-odour memories, where flies associate an odour stimulus with electric shock to specific day time, and the modulation of clock neurons. First results indicate that time-odour memories may depend on the same signalling routes as described for the circadian modulation of memory performance. Further, clock neurons seem to be modulated by octopamine which allows that the integration of the time of day depends on the physiological state of the flies. Taken together, the research project has provided a lot of new insights into the neuronal correlates of time integration in memories. With these results, further studies can follow to understand the underlying interaction of the circadian clock and memory processes holistically.
Publications
- (2018); A comprehensive anatomical map of the peripheral octopaminergic/tyraminergic system of Drosophila melanogaster. Scientific Reports 8:15314
Pauls D, Blechschmidt C, Frantzmann F, el Jundi B, Selcho M
(See online at https://doi.org/10.1038/s41598-018-33686-3) - (2019); Neuropeptides in modulation of Drosophila behavior: how to get a grip on their pleiotropic actions. Current Opinion in Insect Science. 36:1-8
Nässel DR, Pauls D, Huetteroth W
(See online at https://doi.org/10.1016/j.cois.2019.03.002) - (2019); Reward signaling in a recurrent circuit of dopaminergic neurons and peptidergic Kenyon cells. Nature Communications 10:3097
Lyutova R, Selcho M, Pfeuffer M, Segebarth D, Habenstein J, Rohwedder A, Frantzmann F, Wegener C, Thum AS, Pauls D
(See online at https://doi.org/10.1038/s41467-019-11092-1) - (2020); A novel thermal-visual place learning paradigm for honeybees. Frontiers in Behavioral Neuroscience. 14:56
Scheiner R, Frantzmann F, Jäger M, Mitesser O, Helfrich-Förster C, Pauls D
(See online at https://doi.org/10.3389/fnbeh.2020.00056) - (2021); Endocrine fine-tuning of daily activity patterns under nonstarving conditions in Drosophila. Current Biology 31:4076-4087
Pauls D, Selcho M, Räderscheidt J, Amatobi KM, Fekete A, Krischke M, Hermann-Luibl C, Ozbek Unal AG, Ehmann N, Itskov PM, Kittel RJ, Helfrich-Förster C, Kühnlein RP, Müller MJ, Wegener C
(See online at https://doi.org/10.1016/j.cub.2021.07.002)
