A collaboration between the Mann and Molnár Groups has discovered that a small group of specialised brain cells plays a powerful role in keeping us alert and helping our brains process sensory information. These neurons, located deep in the brain’s cortex, respond to dopamine, a chemical messenger linked to motivation and attention, and act like a “wake-up switch” that helps the brain shift into an active, ready state.
The study (published in Frontiers in Neuroanatomy here) focused on a subpopulation of neurons located mostly in layer 6 of the cortex that express the Drd1a dopamine receptor. The team used advanced genetic techniques in mice to silence these neurons from birth, effectively shutting down their ability to send chemical messages to other brain cells. What they found was both surprising and revealing.
Brain wiring can start without signals — but needs them later
Even without the ability to send normal signals, these neurons still managed to reach their correct place in the brain and formed basic wiring with other regions. This suggests that some aspects of brain development — especially the initial layout of connections — can happen without traditional communication between neurons. However, over time, the silenced neurons shrink and die. This shows that while early brain development might be able to get by without certain signals, maintaining a healthy and functional brain in the long term does require active communication between neurons.
More brain cells — but not necessarily better
Interestingly, adult mice with silenced Drd1a neurons had a higher density of these neurons in a key sensory part of the brain than normal mice. The scientists think this may be due to a failure in the brain’s normal process of synaptic pruning. As the brain matures, it prunes away unnecessary neurons to streamline processing. Without proper signalling from the Drd1a-marked neurons, some cells may have escaped this pruning process. Moreover, it is possible that due to the lack of signalling, the brain will try to “compensate” by keeping more neurons alive. Unfortunately, functional evidence suggests that this compensatory mechanism is not sufficient to sustain dopaminergic-driven cortical activation.
Dopamine’s role in boosting brain activity
To test how dopamine affects brain activity, the researchers applied dopamine-like substances to brain tissue slices. In healthy brains, this dopaminergic-induced activity boosts brain rhythms and promotes cortical arousal. This allows us to pay attention and correctly process the sensory stimuli from our surroundings. In brains with silenced Drd1a neurons, dopaminergic-induced activity disappeared. Interestingly, even the substances that do not directly act on the Drd1a receptor couldn’t induce activity.
This strongly suggests that these neurons are essential for the brain’s response to dopamine, helping to “switch on” the cortex when it’s time to pay attention or respond to the world.
A pathway to understanding brain disorders
Deep layer neurons have been reported to be involved in neurodevelopmental psychiatric conditions such as ADHD, autism, and schizophrenia. These findings may have implications for understanding the mechanism behind this involvement, where dopamine systems and brain arousal are often disrupted.
‘Our study highlights a hidden group of neurons that help tune the brain’s activity levels. They seem to act like a key relay station taking in important signals and helping the brain get ready to process the world’, said Auguste Vadisiute and Fernando Messore, co-lead authors of the study.
‘This small group of cortical neurons that were previously considered developmental remnants in the adult brain have unique responsiveness to neuromodulators (neurotensin, orexin, dopamine) and very extensive connectivity. We shall continue to explore the receptor-mediated neuronal modulation and behavioural correlates with future investigations poised to explore therapeutic exploitation, blending molecular precision with systems-level understanding.’ said Professors Ed Mann and Zoltán Molnár, co-corresponding authors of the paper.