Mouse model shows possibilities of reversing memory deficits after repeated mild head impacts
By Zoe Heart. This article was initially published in the 2/1/24 edition of our Concussion Update newsletter; please consider subscribing.
A study published in The Journal of Neuroscience found that in mice, memory loss after being subjected to a “high frequency of mild head impacts” was linked to a deficiency in synaptic plasticity rather than “a loss of neural infrastructure.” (Synaptic plasticity is the ability of neurons to adjust the strength of their connections.) The mice were given head impacts designed to be the equivalent of one week of head impact exposure for the average collegiate football player. The researchers found that memory could be returned to the mice by artificially strengthening neural connections through the stimulation of mice’s memory engrams (units that control neural communication in response to stimulus). According to lead author Daniel Chapman and his team, these results suggest the exciting prospect that post-trauma amnesia and poor memory ”are not indicative of “irreversible neuronal damage.” Instead, there is the possibility that “cognitive impairment caused by head impact” could be clinically reversed.
Chapman and his team divided mice into two groups, “Sham” and “HHFI” (High-Frequency Head Impact). They then conditioned both groups of mice with a new memory, which combined aversive experiences (noises and other cues) as the mice ran through a test or maze. Afterward, they exposed the HHFI group of mice “to a high frequency of mild head impacts for one week.”
After the HHFI group experienced one week of repeated head trauma, the researchers presented both groups of mice with their previously conditioned fear response cues. Only Sham mice exhibited a fearful response; the HHFI mice could not remember the new memory they had gained prior to the head impacts. Through studying the mice’s hippocampal neurons and memory engrams, the team determined that HHFI mice had a comparable number of hippocampal neurons as Sham mice but decreased levels of synaptic plasticity.
However, after the researchers used optogenetics to re-stimulate neural connections in HHFI mice, the HHFI group could recall their fear response (connected to memory of the room where they learned the fear response) at an identical level to that of the Sham group. In other words, mice that had suffered repeated head injuries demonstrated fully functional memory recall after treatment.
This study was exclusive to fear responses in mice; more research is necessary to determine whether engram-stimulation therapies can be applied to humans suffering post-traumatic amnesia. The treatment given to the mice was an invasive use of lasers, so it could not be used on humans, but the researchers foresee the development of noninvasive techniques.
However, Chapman and his team write that these results have exciting implications, explaining that they “provide new data on how memories are stored and retrieved, uncover new insights on the mechanisms of amnesia, and reveal new targets for treating head impact-induced memory loss.”
