A Critical Period for Development of the Prefrontal Cortex
Post by Megan McCullough
The takeaway
Thalamic activity during a critical period in development plays a role in shaping the prefrontal cortex. Inhibiting thalamic input to the prefrontal cortex during this critical period creates long-lasting anatomical and behavioral effects that persist into adulthood.
What's the science?
Critical periods are windows of time after birth where there is increased plasticity in the brain. Experiences during this period are essential for proper development and disruptions to learning during this time can have long-lasting consequences. Although previous research identifies a critical period for signals from the thalamus leading to the development of the sensory cortex, it is unknown whether a critical period exists for thalamic activity shaping the development of the prefrontal cortex. The prefrontal cortex is a crucial brain region for study, as this region is functionally responsible for processes like memory and attention, and prefrontal cortex dysfunction is linked to neurodevelopmental disorders. This week in Nature Neuroscience, Benoit and colleagues aimed to examine the role of thalamic activity in the maturation of the prefrontal cortex by inhibiting the thalamus in adolescent mice.
How did they do it?
First, the authors inhibited the mediodorsal and midline thalamus in a group of adolescent mice by injecting the mice with a virus containing hM4Dgi, a designer inhibitory receptor. To test the long-term cognitive effects of inhibiting thalamic activity in adolescence, these mice completed working memory and attention tasks – tasks that rely on the prefrontal cortex – in adulthood. The authors then assessed changes in prefrontal cortex circuit function due to thalamic inhibition via slice physiology, measuring excitatory and inhibitory activity in a layer that receives projections from the thalamus. Next, a fluorescent protein (GFP), was injected into the adult mice to identify any anatomical changes in neuronal tracts from the thalamus.
These tests were administered to the adult mice who had experienced the thalamic disruption in adolescence as well as to adult mice who had experienced the thalamic disruption in adulthood. The authors studied both age groups to identify the existence of a critical period for prefrontal cortical maturation due to signals from the thalamus.
What did they find?
The authors found that inhibiting the thalamus during adolescence leads to deficits in circuit function in the prefrontal cortex as well as cognitive deficits that persist into adulthood. These deficits were not found when the thalamus was inhibited in adult mice. These results suggest that there is a critical period in development for the maturation of the prefrontal cortex through excitatory input from the thalamus; disrupting these signals during this time period has long-lasting anatomical, functional, and cognitive effects. Specifically, in the adult mice that underwent thalamic inhibition during their adolescence, there was reduced excitatory drive to pyramidal cells in the prefrontal cortex, a reduction in the density of thalamic-prefrontal projections, and reduced performance on memory and attention tasks. Importantly, the authors also found that the behavioral deficits seen in adulthood could be rescued through excitation of the thalamus in the adult mouse.
What's the impact?
This study is the first to show that thalamic input to the prefrontal cortex during a critical period in development is essential for proper prefrontal maturation. Inhibiting activity in the thalamus led to deficits that persisted into adulthood. This has therapeutic relevance as neurodevelopmental disorders such as schizophrenia are linked to disruptions in proper cortical development thought to occur in adolescence.
