Neural substrates in the postpartum brain for flexible maternal care

Flexible infant-oriented maternal behavior is driven by multisensory offspring cues. An example of behavioral flexibility in maternal mice (dams) is the rapid transition from nursing in the nest to exiting the nest in search of misplaced pups. This involves sensory competition between distress calls, emitted by pups outside the nest, and somatosensory contact with pups inside the nest. Inflexible maternal behavior can be a symptom of postpartum depression. Although selective serotonin reuptake inhibitors are a common treatment, it remains elusive how serotonin gates responses to infant cues in maternal brain networks. Here, we investigate the neural substrates underlying processing of competing infant cues, and their modulation by serotonin. We identified a neural hub for infant cue processing: calbindin-expressing neurons in the posterior intralaminar thalamus (PIL^cb). Using channelrhodopsin-assisted circuit mapping, we found that PIL^cb neurons receive input from primary sensory nuclei and send output to the paraventricular nucleus to control oxytocin release and maternal behavior. PIL^cb neurons in dams were more excitable than in virgins, and showed a particular preference for input frequencies consistent with the frequency range of pup calls. We observed a dense distribution of serotonergic fibers in PIL, and bath application of serotonin depolarized PIL^cb neurons. Using calcium imaging we found that auditory and tactile stimuli elicited neural responses in PIL. Finally, using GRAB_5-HT sensor we found that serotonin levels in PIL are modulated by pup calls. Our findings establish PIL as a bottleneck station, uniquely positioned for multisensory processing of competing infant cues, potentially modulated by serotonin.