OR06-3 Prolactin Acts on Glutamatergic Neurons in the Ventromedial Nucleus of the Hypothalamus to Modulate Maternal Aggression

Social interactions between a mother, her child and her family members are influenced by hormones acting on complex neural circuitry, with different regions of the brain regulating specific aspects of behaviour. Maternal aggression, a component of maternal behaviour, is conserved across many species including humans, and enables a mother to respond to and protect her young from danger or a perceived threat. It is currently unclear how the hormonal changes of pregnancy and lactation contribute to this behavioural change. Previously we have shown that the hormone prolactin acts throughout the neural network that governs maternal behaviour, to promote the onset of maternal nursing behaviour after offspring are born. By conditionally deleting prolactin receptors (Prlr) from glutamatergic neurons (Prlr(lox/lox)/VGlut-Cre) we have identified a homogenous population of prolactin-sensitive glutamatergic neurons in the hypothalamic ventromedial nucleus (VMN). As the VMN is central to neural circuitry governing aggressive behaviour in both sexes, we hypothesised that prolactin acts in the VMN to induce the onset of maternal aggression. Surprisingly, in the absence of prolactin signalling in glutamatergic neurons, maternal mice display heightened rather than reduced aggression towards intruders. Wildtype juvenile male mice were placed into the home cage of lactating control (Prlr(lox/lox)) and glutamatergic neuron-specific Prlr knockout (Prlr(lox/lox)/VGlut-Cre) mice, and aggressive behaviour recorded. Lactating Prlr(lox/lox)/VGlut-Cre mice were more aggressive, showing significantly reduced latencies to attack (53.6 ± 25.2 sec vs 415.6 ± 116 sec in control mice), increased episodes of attacking (19.4 ± 3.0 vs 9.2 ±3.7 in control mice) and a greater time spent attacking (228.4 ± 32.0 sec vs 88.4 ± 37.4 sec in control mice). We examined whether this was specifically mediated by glutamatergic neurons, by comparing intruder-induced aggression to lactating mice with Prlr conditionally deleted from GABAergic neurons (Prlr(lox/lox)/VGat-Cre mice). The aggressive behaviour of lactating Prlr(lox/lox)/VGat-Cre mice was not different to controls. We also investigated whether this change in behaviour was specific to maternal aggression or whether Prlr(lox/lox)/VGlut-Cre mice show intruder-induced aggression as virgins. In non-pregnant mice, neither Prlr(lox/lox)/VGlut-Cre or control Prlr(lox/lox) mice displayed aggressive behaviour towards juvenile male mice. Finally, we bilaterally administered an AAV-Cre into the VMN of adult Prlr(lox/lox) mice to specifically delete Prlr form the VMN. These mice showed significantly heightened maternal aggression compared to AAV-control injected mice. These data demonstrate a novel role for prolactin in aggressive behaviour, with prolactin having important involvement in moderating the level of aggression in a lactating mouse.