Recovering amnestic memories from the repeat head impact brain

PROJECT SUMMARY (ABSTRACT)
An athletic career filled with head impacts (HI) predisposes athletes to memory impairments and is a
risk factor for dementias including Alzheimer’s disease. While proteinopathy is clearly linked to brain
dysfunction in the late stages of these disease, memory problems are also a common symptom in
reported cases with early-stage disease – and even those cases with no neurodegenerative disease
pathology. To understand the nature of the chronic memory impairments caused by HI, we are focused
on the physiological changes that occur in the brain after exposure to a high frequency of non-damaging
HI (HFHI), and comparing our results to a single severe single TBI. Our preliminary data shows that
exposing mice to HFHI causes an adaptive response in excitatory synapses. These adaptations occur
at the cost of normal brain function, with widespread and prolonged impairments in learning and
memory. This synaptic dampening is permanent, and does not spontaneously reverse. In this proposal
we aim to determine if we can reverse chronic synaptic dysfunction in the injured brain, and recall a
forgotten memory.
In this proposal we will test the hypothesis that HFHI disrupts synaptic transmission within the
memory circuits of the hippocampus, and that activation of engram neurons can override these
cognitive deficits and reanimate a forgotten memory.
These data will allow us to test if it will be possible to treat cognitive impairments by targeting the
synapse in different types of TBI. This will have profound implications for the millions of people living
with cognitive and behavioral dysfunction after head impact, and could be harnessed to reduce the
number of TBI patients that progress to develop Alzheimer’s disease each year.

Grant Number: 5R01NS121316-03
NIH Institute/Center: NIH
Principal Investigator: MARK BURNS