The perinatal period is a highly plastic period during which environmental factors can shape the development of the brain. One of the major environmental inputs at this stage is maternal care. Poor maternal care and maternal neglect have been implicated in an array of mental health issues. This is most clearly observed in children that spent early life in orphanages with a low caregiver/infant ratio. However, little is known on how maternal presence regulates brain activity in the infant. Neural activity in early life shapes circuit development and can have life-long consequences on brain function. In our preliminary work, we found that maternal presence/absence from the nest regulates the activity of the prefrontal cortex of rat pups at post-natal day 11. Using wireless local field recording, we will test the role of the serotonergic system in the regulation of pups? brain activity by maternal presence/absence from the nest. In our pilot study, we found preliminary evidence suggesting that: (a) maternal presence increases LFP power in low-frequency bands in P11 rat pups in the PFC; (b) serotonergic signaling through 5-HT2 receptors is necessary for this modulation; and (3) enhancing serotonergic signaling, using a serotonin-selective reuptake inhibitor, in isolated P11 rat pups produces an enhancement in LFP power in low-frequency bands similar to the effect produced by maternal presence. The purpose of this R03 proposal is to increase the sample size of these groups to confirm our preliminary results. This work can reveal the mechanism by which maternal presence regulates brain activity in the pup and sets up a paradigm to study environmental regulation of brain activity in the pup.

Public Health Relevance

One of the most important environmental factors influencing brain development, and later vulnerability to maladaptive behaviors, is maternal care. In this study, we propose to test the hypothesis that the mother?s presence or absence regulates the activity of key prefrontal regions of the brain in 11 day-old rat pups through the serotonergic system. Understanding how maternal presence affects neural activity during early life would provide key insights into how maternal care affects the adaptive/maladaptive development of brain circuits.

Agency
National Institute of Health (NIH)
Institute
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Type
Small Research Grants (R03)
Project #
5R03HD094978-02
Application #
9656162
Study Section
National Institute of Child Health and Human Development Initial Review Group (CHHD)
Program Officer
Griffin, James
Project Start
2018-04-01
Project End
2021-03-31
Budget Start
2019-04-01
Budget End
2021-03-31
Support Year
2
Fiscal Year
2019
Total Cost
Indirect Cost
Name
Nathan Kline Institute for Psychiatric Research
Department
Type
DUNS #
167204762
City
Orangeburg
State
NY
Country
United States
Zip Code
10962
Shah, Relish; Courtiol, Emmanuelle; Castellanos, Francisco X et al. (2018) Abnormal Serotonin Levels During Perinatal Development Lead to Behavioral Deficits in Adulthood. Front Behav Neurosci 12:114
Courtiol, Emmanuelle; Wilson, Donald A; Shah, Relish et al. (2018) Maternal Regulation of Pups' Cortical Activity: Role of Serotonergic Signaling. eNeuro 5: