Adaptation of hypothalamic CRH neuron responses to stress and pup cues during motherhood

The adaptation of stress responses during motherhood is critical for the well-being of the mother and the offspring. Stress responses are controlled by corticotropin-releasing hormone (CRH) neurons in the paraventricular nucleus (PVN) of the hypothalamus. Although it is commonly believed that the activity of CRH neurons is dampened during motherhood, this hypothesis has not been directly tested. Using fibre photometry, we obtain optical recordings of PVN CRH neuron activity in freely behaving mice. Contrary to expectations, CRH neuron excitation in response to external stressors is not suppressed during lactation compared to virgin mice. However, we observe significant reductions in Crh mRNA expression and corticosterone release following stress in the lactating mice. In a pup retrieval task, there are large reductions of CRH neuron activity upon pup retrieval only in lactating mice. When lactating mice are in the presence of an inaccessible pup that could not be physically retrieved, this induces an amplified level of CRH neuron activity. These data show that during motherhood, CRH neuron activity is not globally suppressed. More importantly, we show for the first time that during lactation, CRH neuron responses to pup cues are amplified. These adaptations likely facilitate maternal behaviours that promote offspring survival.