Effects of early life adversity and adolescent basolateral amygdala activity on corticolimbic connectivity and anxiety behaviors

Background

Too often, life experiences that cause emotional trauma are not properly taken into account when we talk about the optimal development of a child. Indeed, these adversities might impact the natural development of our brain, especially when they occur before adulthood. Society tends to make a clear distinction between physical injuries and emotional ones, considering the latter not as important or worthy of acknowledgment as the former. Invisible pain doesn’t seem to require the same attention and concern as an open wound. Despite this missing recognition, the reality is that emotional injuries and experiences can have a very strong impact: they can change the brain’s circuitry.

Indeed, what happens in our everyday life plays a fundamental role in the development and formation of connections between different areas of the brain. In this preprint, the focus lies on two sensitive periods of neuronal formation: early postnatal life and adolescence. During early postnatal life the synapses in the limbic regions are established, while the prefrontal cortex (PFC) matures during adolescence. Early life adversity (ELA) might impact these crucial processes. Indeed, after birth, the brain “expects” a specific quantity and quality of stimuli in order to develop typically. If this expectation is not met, it might lead to altered maturation of the post-natal brain. Perhaps unsurprisingly, ELAs can possibly lead to anxiety and major depressive disorders. These symptoms often emerge in adolescence and continue throughout adulthood.

Before diving into this preprint, it is important to understand the “relationship” between the PFC and the basolateral amygdala (BLA). The PFC receives information from the BLA, the primary input nucleus of the amygdala. In healthy rats, these connections increase throughout adolescence allowing the processing of emotional information and environmental stimuli. The main idea expressed by the preprint authors is that early challenges to the amygdala might induce possible changes in efferent projections. This might cause problems when the circuit is recruited during adolescence. Indeed, pre- and post-synaptic plasticity in the PFC depends on specific, sensitive periods of growth.

Key Findings

Early life adversities trigger hyperactivity of the BLA

In order to better understand the consequences of early life adversity, the authors chose a maternal model of separation (MS) in rats. Upon separation, rats show similar changes in the corticolimbic circuit as well as in anxiety levels when compared to humans. The preprint authors showed that separation induced hyperinnervation of the PFC from glutamatergic BLA projections in rats, as well as enhanced anxiety-like behaviour as measured by the acoustic startle response (ASR). These effects were seen in adolescent rats: as early as postnatal day 40 in male rats, and 30 in females, which corresponds to early-mid adolescence in humans. The authors hypothesized that ELA leads to pre- and post-synaptic changes to BLA-PFC connectivity via hyperactivity within the developing BLA.

Sex differences and PFC plasticity

The same analysis in late-adolescence showed an increase in innervation, but only in male mice. The lack of this phenomenon in females suggests that synaptic pruning, a process that occurs between early childhood and the onset of puberty, might go back to baseline levels. During this process, unnecessary synapses are eliminated in order to remove needless neuronal structures from the brain. This also suggests a more extensive synaptic pruning in females compared to males. Inhibiting the BLA during early-mid adolescence was not enough to reverse the observed changes. The inability of presynaptic BLA inhibition to reverse hyperinnervation or behavioural changes suggests that postsynaptic plasticity in the PFC may be driving these effects. In a nutshell, MS increases postsynaptic receptor expression in the PFC which is associated with anxiety-like behaviours.

To conclude, this study underlines the importance of studying postsynaptic mechanisms in the PFC to fully understand the developmental impacts of ELA on corticolimbic connectivity and related behaviours.

Why I picked this preprint

I found this preprint to be of high quality and fascinating as it clearly shows that psychological trauma can have an impact on the brain by modifying its connections and circuitry. I think this study is a very good example of research that shows that depression and/or anxiety are real pathologies that should be recognized as such.

 

Questions for the authors

• Are you planning to investigate the post-synaptic plasticity of the PFC in more detail?
• Are you planning to explore the cause of the sex-specific differences you have observed?
• Will you continue working on depression and anxiety-like disorders?

 

doi: https://doi.org/10.1242/prelights.37922

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