Electrophysiological insights into the enduring effects of early life stress on the brain

Abstract

Increasing evidence links exposure to stress early in life to long-term alterations in brain function, which in turn have been linked to a range of psychiatric and neurological disorders in humans. Electrophysiological approaches to studying these causal pathways have been relatively underexploited. Effects of early life stress on neuronal electrophysiological properties offer a set of potential mechanisms for these susceptibilities, notably in the case of epilepsy. Thus, we review experimental evidence for altered cellular and circuit electrophysiology resulting from exposure to early life stress. Much of this work focuses on limbic long-term potentiation, but other studies address alterations in electrophysiological properties of ion channels, neurotransmitter systems, and the autonomic nervous system. We discuss mechanisms which may mediate these effects, including influences of early life stress on key components of brain synaptic transmission, particularly glutamate, GABA and 5-HT receptors, and influences on neuroplasticity (primarily neurogenesis and synaptic density) and on neuronal network activity. The existing literature, although small, provides strong evidence that early life stress induces enduring, often robust effects on a range of electrophysiological properties, suggesting further study of enduring effects of early life stress employing electrophysiological methods and concepts will be productive in illuminating disease pathophysiology.

Early Life Stress Enhancement of Limbic Epileptogenesis in Adult Rats: Mechanistic Insights

“…in susceptible individuals, brain insults early in life trigger a cascade of neurobiological processes that ultimately – often after years or decades - result in an epileptic state marked by spontaneous recurrent limbic seizures [4], [84], a framework sometimes termed the ‘two-hit’ model. Thus, undoubtedly, multiple causal pathways are involved linking early stress to later epilepsy [17], [85], but we suggest the present findings are consistent with a large body of literature about pathogenic effects of sustained glucocorticoid release on limbic structures [6], [19], [21], [86]. Based on this literature, we speculate that early life stress ‘programming’ of HPA axis function produces hyper-reactivity, leading to exaggerated CORT release during kindling seizures.…”

Indiscriminate Amygdala Response to Mothers and Strangers After Early Maternal Deprivation

“…In addition, PI children have been shown to exhibit amygdala hyperactivation to emotionally arousing faces (38). These findings with human samples mirror the effects of maternal deprivation observed in several other altricial species (24, 25, 39, 40). …”

Unraveling the Time Domains of Corticosteroid Hormone Influences on Brain Activity: Rapid, Slow, and Chronic Modes

“…An extensive number of studies reported that perinatal stress changes synaptic properties in adulthood, both under "basal" conditions (i.e., when animals are not stressed) and when brain tissue of adult animals is exposed to a surge of corticosteroid hormones (for review, see also Ali et al, 2011) (Supplemental Table IV). How perinatal stress can induce such lasting effects on excitability has not yet been addressed.…”