# Effects of Early Life Stress on the Developing Basolateral Amygdala-Prefrontal Cortex Circuit: The Emerging Role of Local Inhibition and Perineuronal Nets

## TL;DR

Early life stress affects brain circuits involved in emotional regulation, potentially leading to anxiety and depression through changes in local inhibition and perineuronal nets.

## Contribution

This paper highlights the role of local inhibitory neurons and perineuronal nets in mediating the long-term effects of early life stress on emotional behavior.

## Key findings

- Early life stress alters glutamatergic circuits and local inhibitory interneurons in the corticolimbic system.
- Changes in inhibitory neurons and perineuronal nets may contribute to psychiatric disorders like anxiety and impaired fear extinction.
- The effects of ELS on brain circuits show sex- and hemispheric-dependent patterns in both humans and rodents.

## Abstract

The links between early life stress (ELS) and the emergence of psychopathology such as increased anxiety and depression are now well established, although the specific neurobiological and developmental mechanisms that translate ELS into poor health outcomes are still unclear. The consequences of ELS are complex because they depend on the form and severity of early stress, duration, and age of exposure as well as co-occurrence with other forms of physical or psychological trauma. The long term effects of ELS on the corticolimbic circuit underlying emotional and social behavior are particularly salient because ELS occurs during critical developmental periods in the establishment of this circuit, its local balance of inhibition:excitation and its connections with other neuronal pathways. Using examples drawn from the human and rodent literature, we review some of the consequences of ELS on the development of the corticolimbic circuit and how it might impact fear regulation in a sex- and hemispheric-dependent manner in both humans and rodents. We explore the effects of ELS on local inhibitory neurons and the formation of perineuronal nets (PNNs) that terminate critical periods of plasticity and promote the formation of stable local networks. Overall, the bulk of ELS studies report transient and/or long lasting alterations in both glutamatergic circuits and local inhibitory interneurons (INs) and their associated PNNs. Since the activity of INs plays a key role in the maturation of cortical regions and the formation of local field potentials, alterations in these INs triggered by ELS might critically participate in the development of psychiatric disorders in adulthood, including impaired fear extinction and anxiety behavior.