Altered activity within the social behavior neural network in adolescent rats following prenatal alcohol exposure and/or early-life adversity

Abstract

Background: Social behavior relies on the dynamic, complex, and coordinated activity of a highly conserved "social behavior neural network," which includes the olfactory bulb (OB), piriform cortex (PCX), lateral septum, medial prefrontal cortex (mPFC), amygdala, paraventricular nucleus of the hypothalamus (PVN), and ventral hippocampus. Prenatal alcohol exposure (PAE) is known to disrupt social behavior development, leading to lifelong social functioning impairments. Individuals with PAE are at heightened risk of experiencing early-life adversity (ELA), which independently affects social behavior development; however, little is known about the combined effects of PAE and ELA on social behavior.

Methods: We previously demonstrated that PAE and ELA impact social recognition memory throughout adolescence; here, we combine animal models of PAE and ELA to gain insight into both independent and interactive effects of these insults on social behavior network neural activity in both early and late adolescent male and female rats. We measured neural activity (c-fos mRNA expression) across the network following social recognition memory testing.

Results: Our findings indicate that both PAE and ELA are associated with altered neural activity in regions supporting social recognition memory, notably the OB, PCX, mPFC, amygdala, and PVN. The direction of these effects and specific regions impacted vary by sex and age at assessment. Importantly, different brain areas exhibit distinct sensitivities to each type of insult, with PAE generally resulting in hypoactivity of the amygdala and ELA altering mPFC activity.

Conclusions: These data contribute to a more complete social neurobehavioral profile, accounting for both PAE and ELA, to support earlier diagnoses and interventions.

Keywords: c‐fos; adolescence; early‐life adversity; neural activity; prenatal alcohol exposure; social behavior neural network.

FIGURE 1

Experimental timeline and regions of interest. (Top) Schematic overview of the experimental design. Prenatal alcohol exposure (PAE) occurred throughout gestation (gestational days [G]1–22). Early‐life adversity (ELA) was induced between postnatal days (P)8–12 using the low bedding model. Behavioral and neurobiological assessments were conducted during early (P30) and late (P45) adolescence. (Bottom) Representative coronal atlas sections illustrating the regions of interest (ROIs) analyzed for c‐fos expression. Color‐coded brain regions include the olfactory bulb (OB), anterior cingulate cortex (ACC), prelimbic cortex (PrL), infralimbic cortex (IL), lateral septum (LS), magno‐ and parvocellular divisions of the paraventricular nucleus (magnoPVN; parvoPVN), supraoptic nucleus (SON), amygdala nuclei: lateral (LA), basolateral (BLA), centro‐lateral (CeL), centro‐medial (CeM), medial (MeA), and cortical (CoA), ventral hippocampus: CA1, CA3, and ventral subiculum (vSub), shown with anterior–posterior (AP) coordinates relative to bregma (Paxinos & Watson, 2005).

FIGURE 2

Olfactory bulb (OB), piriform cortex (PCX), and lateral septum (LS) c‐fos expression following social recognition testing in male and female prenatal alcohol exposed (PAE) rats, with and without early‐life adversity (ELA). Bars represent the mean ± SEM of the mean gray value of c‐fos expression in the OB (A–D), PCX (E–H), and LS (I–L) (n = 4–8 for all groups). *Post hoc comparisons following a significant interaction between prenatal treatment and rearing condition; ^†PAE animals are significantly different from controls regardless of rearing condition; ^$ELA animals are significantly different from normally reared animals regardless of prenatal treatment; for C, ^#PAE normally reared females are different from control normally reared females based on a priori comparison; for G, ^#Control ELA females are different from control normally reared females based on a priori comparison.

FIGURE 3

Medial prefrontal cortex c‐fos expression following social recognition testing in male and female prenatal alcohol exposed (PAE) rats, with and without early‐life adversity (ELA). Bars represent the mean ± SEM of the mean gray value of c‐fos expression in the ACC (A–D), PrL (E–H), IL (I–L), and OFC (M–P) (n = 6–8 for all groups). *Post hoc comparisons following a significant interaction between prenatal treatment and rearing condition; ^$ELA animals are significantly different from normally reared animals regardless of prenatal treatment; ^#Control ELA males are different from control normally reared males based on a priori comparison.

FIGURE 4

Amygdala c‐fos expression following social recognition testing in male and female prenatal alcohol exposed (PAE) rats, with and without early‐life adversity (ELA). Bars represent the mean ± SEM of the mean gray value of c‐fos expression in the BL (A–D), LA (E–H), MeA (I–L), CeM (M–P), and CeL (Q–T) (n = 7–8 for all groups). ^†PAE animals are significantly different from controls regardless of rearing condition.

FIGURE 5

Paraventricular nucleus of the hypothalamus c‐fos expression following social recognition testing in male and female prenatal alcohol exposed (PAE) rats, with and without early‐life adversity (ELA). Bars represent the mean ± SEM of the mean gray value of c‐fos expression in the magnoPVN (A–D) and parvoPVN (E–H) (n = 7–8 for all groups). ^†PAE animals are significantly different from controls regardless of rearing condition; ^$ELA animals are significantly different from normally reared animals regardless of prenatal treatment.

FIGURE 6

Ventral hippocampus c‐fos expression following social recognition testing in male and female prenatal alcohol exposed (PAE) rats, with and without early‐life adversity (ELA). Bars represent the mean ± SEM of the mean gray value of c‐fos expression in the CA1 (A–D), CA3 (E–H), DG (I–L), and SubV (M–P) (n = 7–8 for all groups).