Human astrocyte. The vivid color is from GFP, not drugs.
The real news is the importance of a type of brain cells called astroglia, which have long been ignored while researchers focus on neurons. THC, the psychoactive chemical in marijuana, impairs working memory by connecting to astroglia, according to a new paper published in Cell. So the star-shaped astroglia turn out to be the real star of this study.
How the Heck:
- Researchers injected synthetic THC into the hippocampuses of rats and recorded their brain activity, finding that THC weakened connections between specific neurons.
- Then they took three types of mutant mice: two without THC receptors in their neurons and another without THC receptors in their astroglia. When they again injected THC, it had the same, original effect on the first two mutants and no effect on rats with astroglia that had no THC receptors. That suggests the THC acts directly on astroglia rather than neurons.
- The team then showed that the signaling molecule glutamate is used to communicate between astroglia and neurons, in this case causing neurons to weaken their connections with each other. (For more detail on the molecular mechanism, read Mo Costandi’s explanation at the Guardian.)
Dude, Where’s My Car?
- So some brain cells react to THC, but does it have any effect on the actual behavior? The researchers essentially repeated the above experiments but instead of examining neurons, they turned to animals in mazes.
- THC made the animals pretty awful at navigating Morris water mazes and T-mazes, except when the mouse had mutant astroglia that could not respond to THC. Turn off the astroglia and you turn off the mechanism for weakening neuronal synapses.
From Glue to Glutamate:
- Astroglia are one type of glia, which means “glue” in Greek, telling you just how important neuroscientists once considered them. Glia is really a catch-all term for any brain cell that is not a neuron, and they make up over half the cells in your brain.
- Functions of astroglia include feeding neurons, giving structural support, regulating the extracellular fluid bathing the brain, and intriguingly, taking up or releasing glutamate, a neurotransmitter usually used for signaling between neurons. That’s one hint astroglia have an active role in brain function.
The Future Holds:
- Astroglia modulate memory and plasticity in the brain—this is strong evidence that glia cells are not sitting passively. They’ve been long neglected in favor of neurons, but that’s changing and this study will tip research further in that direction.
- Brain slices are the basis for a lot of research on how certain drugs affect neurons, but this astroglia study—done in intact brains in animals—suggests that brain slices are inadequate for studying how drugs affect the brain as a system.
- The paper itself and other articles have chattered about how this knowledge can lead to treatmemts minimizing the impairment of working memory, one undesired side effect of medical marijuana use. Not to trivialize it, but we venture that just might be a desired side effect of recreational use. In any case, it’s also worth considering how injecting synthetic THC straight into the brain is pretty different from smoking weed. Marijuana contains other chemicals like cannibidiol, which modulates the effects of THC.
- Ultimately, this paper doesn’t say anything that interesting about the effects of using marijuana. It does show something very cool about astroglia, and it does so by using a chemical called THC, which just so happens to be found in marijuana.
Reference: Han, Jing et al. Acute Cannabinoids Impair Working Memory through Astroglial CB1 Receptor Modulation of Hippocampal LTD. Cell. 02 March 2012. DOI: 10.1016/j.cell.2012.01.037
Image via Wikimedia Commons / Bruno Pascal