All animals sleep, but despite decades of research, neuroscientists still have no clear answer as to why. Now a dramatic new study reveals that sleep may be a fundamental state that even brain cells growing in a dish need.
Swiss neuroscientists Valerie Hinard and colleagues cultured mouse cortical neurons in dishes equipped with arrays of electrodes. This allowed them to record the electrical activity produced by the growing ‘brain’. They also measured the expression of different genes in the neurons, and compared these to gene expression in real mouse brains.
They found that while cultures of neurons started out fired randomly, after about 10 days, the cultures entered a state of synchronized periodic firing, with the whole population of cells firing together in slow cycles of activity – with a frequency of 1 cycle every 5 to 15 seconds. This is extremely slow – by contrast the “slow waves” characteristic of animal sleep cycle about 30 times faster – but the authors say that such ultra-slow waves have been seen in sleeping animals too.
But the dishes could be ‘woken up’ by adding a mixture of neurotransmitters, which abolished the burst cycles. They reappeared about 24 hours later. Gene expression changes in the cells in the ‘sleep’ and ‘wake’ state were significantly correlated with changes seen in real mice deprived of sleep.
Finally – and this might end up being the most important bit – the authors compared the biochemistry of the ‘sleep deprived’ dishes to the ‘well rested’ ones. They found remarkably few major changes, but they did observe a significant increase in the levels of lysolipids.
Lysolipids are breakdown products of phospholipids, which make up the membranes of all living cells. When present in membranes, lysolipids can act as ‘detergents’, distorting their structure. That’s bad. These results suggest that sleep might serve to prevent the build up of lysolipids. If that pans out, it would mean that the function of sleep is very primitive, a fundamental biological necessity for any connected network of neurons, even what amounts to a random medley thrown together on a plate.
This study used cultured mouse neurons, but it’s possible to grow human brain cells in a dish too. The obvious next step will be to check if human neurons exhibit the same sleep/wake-like states – and whether the very slow synchronized firing is really like human sleep. If so, could this help understand insomnia? Narcolepsy? Maybe even jetlag?
It’s also got implications for all other brain-in-a-dish research. Scientists may literally need to ensure that their dishes get enough sleep in future studies.
It’s all very exciting. I don’t study sleep in my own research, but I try to keep up with the literature as I find it very interesting. I’ve covered various aspects of sleep neuroscience previously. So while I’m no expert, this seems to me like truly groundbreaking stuff, and potentially a “game changer” for the whole of neuroscience.
Hinard V, Mikhail C, Pradervand S, Curie T, Houtkooper RH, Auwerx J, Franken P, and Tafti M (2012). Key electrophysiological, molecular, and metabolic signatures of sleep and wakefulness revealed in primary cortical cultures. The Journal of neuroscience : the official journal of the Society for Neuroscience, 32 (36), 12506-17 PMID: 22956841