Oxytocin Primes the Maternal Left Brain in Mice

Oxytocin, a hormone produced in the paraventricular and supraoptic nuclei in the brain, influences maternal functions and behaviors, including parturition, lactation, and bonding. In this study, New York University (NYU) researchers sought to understand precisely how and where the maternal mouse brain responds to pup distress cries in relation to oxytocin signals (Marlin et al. 2015).

The NYU researchers tested the responsiveness of virgin females and experienced mothers (dams) to retrieve pups that had been experimentally removed from a nest. As expected, wild-type C57BL/6 virgin females did not retrieve pups unless co-housed with dams for more than 2 days. In contrast, virgin females carrying an oxytocin-IRES-cre transgene (024234) and infected with a channelrhodopsin adenovirus (a vector for activating oxytoxin-expressing neurons with light) rapidly retrieved pups similar to wild-type dams when those oxytocin neurons were stimulated. Likewise, wild-type virgin females that received stereotactic injections of oxytocin also responded to pup distress calls.

Examination of the primary auditory cortex (AI) in oxytocyin receptor green fluorescent protein-expressing reporter mice (OTXR-eGFP) revealed significantly more oxytocin-positive cells in the left AI than in the right AI. This data suggested that pup retrieval behavior is functionally lateralized, with oxytocin-sensitive neural circuits in the left AI playing a greater role in regulating this behavior. Consistent with this hypothesis, pup retrieval behavior was blocked by pre-treating the left AI with muscimol, a GABAergic neuron inhibitor and neural sedative. Infusing muscimol into the right AI had no effect on pup retrieval.

Examination of excitatory and inhibitory post-synaptic currents in both the left and right AIs and in the left AIs of experience dams versus naïve virgins revealed:

  • The synaptic responses to auditory tones unrelated to pup distress were similar in the left AI of all animals.
  • Excitatory and inhibitory responses to pup distress calls were more precisely balanced in the left AI compared to the right in experienced dams.
  • Excitatory and inhibitory responses were more precisely balanced in the left AI of experienced dams compared to those in naïve virgins.
  • When oxytocin treatment and auditory recordings of pups in distress were given together, the neural synaptic activity profiles in the left AI of virgin females were more similar to those in experienced dams.

These data suggest that the heightened pup retrieval behavior in experienced dams is not simply due to stronger excitatory synaptic inputs to their left AI. Instead, signals in the left AI are more responsive to smaller oxytocin-induced changes in the balance between excitatory and inhibitory synaptic signals, resulting in a greater sensitivity to pup distress.

Together, these findings lend further support to previous research describing dominance in the right ear/left hemisphere circuitry in stimulating maternal responses to auditory cues from offspring. Further, this research suggests that behavior and neural circuitry can be modified through hormonal influence.