EFFECTS OF CHRONIC NEWBORN DISTRESS CALLS ON LATERAL HABENULA FUNCTION AND ADULT-NEWBORN INTERACTIONS IN VIRGIN FEMALE MICE

Postpartum depression, characterized by persistent hopelessness after childbirth, is frequently associated with exposure to excessive infant crying. In rodents, distress pup calls are aversive to virgin female mice and increase neuronal activity in the Lateral Habenula (LHb) – a brain node for aversion encoding and depressive states – subsequently supporting pup retrieval. While retrieval generally stops pup distress, it remains unknown what are the consequences of unresolvable pup distress on adult behavior and LHb synaptic function.
C57BL/6J virgin female mice were exposed to five sessions of morphed pup calls, in an inescapable environment. Mice were divided into two groups: stress and control that were exposed to distress calls (200 ms ISI) and control calls (900 ms ISI), respectively. Following calls exposure, the mice underwent a pup retrieval test to assess adult-newborn interactions and the tail suspension test (TST) to quantify behavioral despair. A separate cohort of mice was instead used to perform ex-vivo patch-clamp recordings following exposure to pup calls.
The results showed that females in the stress group had reduced pup retrieval and, notably, exhibited some pup-attack events compared to the respective control females. These mice also showed increased immobility in the TST, indicating a state of despair. Furthermore, ex-vivo recordings revealed that chronic exposure to distress pup calls reduced both spontaneous excitatory and inhibitory synaptic currents in LHb neurons.
In summary, chronic exposure to excessive distress pup calls modifies LHb synaptic function, disrupts retrieval behaviors, and promotes negative affect, providing insight into the neurological mechanisms underlying disrupted adult-newborn interactions.