In a laboratory in Australia, mice engineered without a working version of the tau protein could learn a task in the moment yet struggled to retain it days later. This observation, drawn from a study published in Nature Communications, has reframed one of neuroscience's more familiar molecules.
For decades tau has been studied mainly through its darker side. In Alzheimer's disease and related conditions it forms tangled clumps inside neurons that track closely with cognitive decline. The new work, however, demonstrates that the same protein is indispensable for the brain to convert fleeting experiences into lasting memories.
Researchers at Flinders University, working with colleagues at the University of New South Wales and Macquarie University, focused on a specific chemical tag. When mice encoded a memory, tau became phosphorylated at threonine 205. This modification proved necessary for remote memory formation weeks after the initial event.
How tau shapes memory circuits
Engram cells are the physical substrate of memory, small ensembles of neurons that fire together when a particular experience is recalled. The study showed that tau phosphorylation at that key site helps recruit the right engram cells and limits activation of neighbouring ones that have no business in the memory trace.
Without this precise selection process, extraneous local cell activation rises. The result is a noisier, less efficient memory that fades. Yet the storage of the memory trace itself does not require tau. When scientists used optogenetic stimulation to activate the relevant neurons directly, they could retrieve remote memories even in animals lacking functional tau.
Why some memories last while others fade has long puzzled scientists and our study shows that tau plays a key role in how the brain forms long-lasting memories. Without it, memories can still form in the moment, but they are weaker.
That observation came from Associate Professor Arne Ittner, one of the lead researchers. His colleague Renée Kosonen put it another way: "Our findings show that tau helps determine which cells are selected to store a memory, shaping how an experience forms a lasting memory trace."
