Maternal deprivation alters expression of neural maturation gene tbr1 in the amygdala paralaminar nucleus in infant female macaques

Abstract

Early parental loss is associated with social-emotional dysregulation and amygdala physiologic changes. Previously, we examined whole amygdala gene expression in infant monkeys exposed to early maternal deprivation. Here, we focus on an amygdala region with immature neurons at birth: the paralaminar nucleus (PL). We hypothesized that 1) the normal infant PL is enriched in a subset of neural maturation (NM) genes compared to a nearby amygdala subregion; and 2) maternal deprivation would downregulate expression of NM transcripts (mRNA). mRNAs for bcl2, doublecortin, neuroD1, and tbr1-genes expressed in post-mitotic neurons-were enriched in the normal PL. Maternal deprivation at either 1 week or 1 month of age resulted in PL-specific downregulation of tbr1-a transcription factor necessary for directing neuroblasts to a glutamatergic phenotype. tbr1 expression also correlated with typical social behaviors. We conclude that maternal deprivation influences glutamatergic neuronal development in the PL, possibly influencing circuits mediating social learning.

Amygdala growth from youth to adulthood in the macaque monkey

“…It is plausible that differences in the environment shape social processing demands (Lambert et al, ; Lederbogen et al, ; Urakawa et al, ) and may have affected the trajectory of amygdala growth. This hypothesis is supported by a body of literature describing the impact of maternal deprivation on amygdala development and connectivity in human and nonhuman primates (de Campo et al, ; Gee et al, ; Olsavsky et al, ; Sabatini et al, ).…”

Immature excitatory neurons develop during adolescence in the human amygdala

“…The cellular architecture and the maturation of PL neurons could therefore be influenced by life experiences during these ages. A recent study found that in the macaque, early life maternal separation leads to lower levels of TBR1 gene expression in the PL later in life 35 . Which cells are affected in the PL and whether this is merely a correlation, or reflects lower amounts of activity in the PL or lower levels of cell maturation remains to be tested.…”

“…Interestingly, lesion studies of the macaque neonatal and adult uncal hippocampus have found fewer immature neurons and more mature neurons in the PL, implying a role for the hippocampal afferents on the maturation of these cells 34 . Early life stress also leads to lower levels of the excitatory neuron transcription factor T-box, brain 1 (TBR1) in the non-human primate PL 35 . A better understanding of the types of neurons in the PL, their relationship to adult neural stem cells, and their developmental dynamics is required to understand the implications of changes in neuropsychiatric disorders 10 and the relationship of the amygdala–hippocampal network to mood 27 .…”

Maternal Deprivation Induces Memory Deficits That Are Reduced by One Aerobic Exercise Shot Performed after the Learning Session

“…It is well established that the exposure to stress in the postnatal period can trigger numerous effects on neuroplasticity, cognitive function, and behavior in adulthood [44], since the postnatal period is critical for the central nervous system development [4]. In this sense, strategies that seek to minimize and/or reverse cognitive damages related to this type of stress are important.…”

“…The early life stress causes neuroendocrine changes associated with social and emotional behavior alterations [2] that may persist throughout life [3]. In humans, especially from the prenatal period until the early years of postnatal life, the brain undergoes a rapid development [4] and is highly sensitive to the influence of positive and negative external experiences [5].…”