Cao, Mingran;
(2025)
Integration of hunger and hormonal state gates infant-directed aggression.
Doctoral thesis (Ph.D), UCL (University College London).
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Abstract
Internal states flexibly shape social behaviour. It has been demonstrated how individual states such as estrous cycle or hunger affect specific behaviours such as mating or aggression. However, animals exhibit multiple such states at any given time. How and where these states are integrated in the brain to shape behaviour remains poorly understood. Here I report how hunger and hormonal state converge onto hypothalamic neurons to shape infant-directed behaviour. I first demonstrate that hunger can rapidly elicit pup-directed aggression in virgin female mice. This behavioural switch is mediated by inhibition of the medial preoptic area (MPOA) by neuropeptide Y (NPY) release from Agouti-related peptide-expressing neurons in the arcuate nucleus of the hypothalamus ($\text{Arc}^{\text{AgRP}}$ neurons). Next, I show that behavioural switching probability is set by hormonal state, with MPOA neurons integrating fluctuating progesterone (P4) to estradiol (E2) ratios throughout the estrous cycle. Both hunger and hormonal state converge onto HCN (hyperpolarization-activated cyclic nucleotide-gated) ion channels, which set MPOA neuronal baseline activity and excitability. This change in excitability alters pup representations, promoting a switch from parental to aggressive behaviour towards pups. Furthermore, I found that the activity of MPOA neurons is not time-locked to aggression, but rather, that MPOA neurons encode pup-directed aggression as a slow, stable state. My work thus provides a neural mechanism for the integration of orthogonal physiological states to flexibly switch social behaviours.
| Type: | Thesis (Doctoral) |
|---|---|
| Qualification: | Ph.D |
| Title: | Integration of hunger and hormonal state gates infant-directed aggression |
| Language: | English |
| Additional information: | Copyright © The Author 2025. Original content in this thesis is licensed under the terms of the Creative Commons Attribution-NonCommercial 4.0 International (CC BY-NC 4.0) Licence (https://creativecommons.org/licenses/by-nc/4.0/). Any third-party copyright material present remains the property of its respective owner(s) and is licensed under its existing terms. Access may initially be restricted at the author’s request. |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences |
| URI: | https://discovery.ucl.ac.uk/id/eprint/10204059 |
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