Abstract
We have recently shown that the cognitive impairments in a mouse model of high-frequency head impact (HFHI) are caused by chronic changes to synaptic physiology. To better understand these synaptic changes occurring after repeat head impact, we used Thy1-GcCAMP6f mice to study intracellular and intercellular calcium dynamics and neuronal ensembles in HFHI mice. We performed simultaneous calcium imaging and local field potential (LFP) recordings of the CA1 field during an early-LTP paradigm in acute hippocampal slice preparations 24 h post-impact. As previously reported, HFHI causes a decrease in early-LTP in the absence of any shift in the input-output curve. Calcium analytics revealed that HFHI hippocampal slices have similar numbers of active ROIs, however, the number of calcium transients per ROI was significantly increased in HFHI slices. Ensembles consist of coordinated activity between groups of active ROIs. We exposed the CA1 ensemble to Schaffer-collateral stimulation in an abbreviated LTP paradigm and observed novel coordinated patterns of post stimulus calcium ensemble activity. HFHI ensembles displayed qualitatively similar patterns of post-stimulus ensemble activity to shams but showed significant changes in quantitative ensemble inactivation and reactivation. Previous in vivo and in vitro reports have shown that ensemble activity frequently occurs through a similar set of ROIs firing in a repeating fashion. HFHI slices showed a decrease in such coordinated firing patterns during post stimulus ensemble activity. The present study shows that HFHI alters synaptic activity and disrupts neuronal organization of the ensemble, providing further evidence of physiological synaptic adaptation occurring in the brain after a high frequency of non-pathological head impacts.
Highlights
Traumatic brain injury (TBI) is one of the most common neurological disorders worldwide
Electrophysiology and pharmacology, we found that the cognitive impairments caused by highfrequency of closed head impacts (HFHI) are due to impaired long-term potentiation (LTP) in the CA3-CA1 synapse and reduced AMPA/NMDA ratio in CA1 pyramidal cells (Sloley et al, 2021)
To assess synaptic plasticity 24 h following HFHI, we investigated early-LTP in the CA3-CA1 circuit (Figure 1A)
Summary
Traumatic brain injury (TBI) is one of the most common neurological disorders worldwide. Repetitive mild TBI (rmTBI), such as those injuries seen in contact sports athletes and members of the armed forces, increases the severity and duration of symptoms (Guskiewicz et al, 2007; Greco et al, 2019). Evidence is emerging to suggest that sub-concussive impacts such as heading a soccer ball or sustained high frequency low amplitude cranial movement seen in professional sled athletes can lead to lasting cognitive symptoms. The mechanism by which high frequency subconcussive impacts can lead to lasting cognitive impairments is poorly understood. Our lab has shown that mice exposed to a highfrequency of closed head impacts (HFHI) have chronic cognitive impairments (Sloley et al, 2021). The HFHI protocol consists of five closed head impacts given in rapid succession every day for 6 days totaling thirty impacts (Main et al, 2017)
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