Borak, Neven; (2024) The modulatory effect of dominance rank on social perception in the mouse hypothalamus. Doctoral thesis (Ph.D), UCL (University College London).

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Abstract

Studies of the neural basis of social dominance hierarchies have focused on how status is learned and represented in a thalamocortical circuit involving mainly the mediodorsal thalamus, the anterior cingulate cortex and the medial prefrontal cortex (mPFC). However, it is unclear how this circuit integrates sensory information about others and leads to distinct behavioural phenotypes for dominant and subordinate individuals in a wide repertoire of social behaviours. This thesis proposes that this is achieved through top-down modulation of the sensory representations of social cues in two hypothalamic areas involved in behavioural decision-making: the medial preoptic area (MPOA) and the ventromedial hypothalamus (VMH). In vivo miniscope recordings in these areas in male mice reveal rank-dependent modulation of neuronal excitability and tuning properties in response to female conspecifics. These functional features in turn predict the propensity for social interaction with females as well as sexual mounting. The position of these nodes in the social cognition pathway with known connectivity to olfactory sensory inputs combined with rank-dependent modulation led to the hypothesis that they serve as integration nodes for information about an animal’s own social rank and that of opponents. It was confirmed that mice detect the rank of unfamiliar opponents through olfactory signals and the encoding of both own and opponent rank variables was individually investigated, however, neither was represented in these areas. Instead, a novel function for the hypothalamus was described in encoding two semi-stable variables with slow dynamics: competitive context and winning state. Finally, a circuit model is proposed where monosynaptic mPFC projections to the hypothalamus achieve sensory modulation and influence winning performance against conspecifics. Optogenetic manipulation of mPFC projections to the MPOA and VMH during competitive behaviour was performed, however, no effect on winning performance was found, instead suggesting a multisynaptic modulatory mechanism or diffuse release of a neuromodulator.

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