Mild Traumatic Brain Injury Alters Hippocampal Sharp-Wave Ripple Properties: Implications in Memory Impairments

Abstract

A large body of evidence has shown that sharp wave ripples (SWRs), highly synchronized oscillations of the local field potential (LFP) in the CA1 pyramidal layer of the hippocampus, play a prominent role in memory consolidation. SWRs typically occur in periods of non-REM sleep, but have also been observed during awake rest periods of animals engaged in cognitive tasks. These events have been observed in rodents, non-human primates, and humans, suggesting they are evolutionarily conserved and contribute to memory formation. Numerous neurological diseases and insults, including traumatic brain injury (TBI), impair learning and memory. Mild TBI (mTBI) is the most prevalent form of TBI, and can cause memory impairments that, in some cases, last for months-to-years. Clinical and experimental studies have shown that these impairments can occur in the absence of visible physical damage to the hippocampus. In the present study, we examined whether an mTBI alters the properties of SWRs in rodents. Seven days after a mild fluid percussion injury (mFPI), recording electrodes were implanted into the CA1 subfield of the hippocampus of sham and injured rats. After seven days of recovery, LFPs and the activity of CA1 neurons were simultaneously recorded. Recordings were carried out when animals were exploring an arena containing two objects, one of which was moved between recording sessions. This allowed us to evaluate how changes in the environment affected SWR incidence and properties. Our data show that compared to uninjured controls, mFPI rats had reduced numbers of SWR events. Of the SWRs recorded, those from mTBI rats had shorter durations, reduced power, and higher frequencies than those in control animals. We also found that the modulation of the activity of CA1 pyramidal neurons by SWRs was markedly impaired in mTBI animals. Taken together, our data indicate that mTBI alters the electrophysiological properties of SWRs and reduces the synchronization of pyramidal neuron activity to SWRs. These electrophysiological changes may have implications in mTBI-associated memory impairments.