Alterations of functional properties of hippocampal networks following repetitive closed-head injury

Abstract

Traumatic brain injury (TBI) is the leading cause of death for persons under the age of 45. Military service members who have served on multiple combat deployments and contact-sport athletes are at particular risk of sustaining repetitive TBI (rTBI). Cognitive and behavioral deficits resulting from rTBI are well documented. Optimal associative LTP, occurring in the CA1 hippocampal Schaffer collateral pathway, is required for both memory formation and retrieval. Surprisingly, ipsilateral Schaffer collateral CA1 LTP evoked by 100 Hz tetanus was enhanced in mice from the 3× closed head injury (3× CHI) treatment group in comparison to LTP in contralateral or 3× Sham CA1 area, and in spite of reduced freezing during contextual fear conditioning at one week following 3× CHI. Electrophysiological activity of CA1 neurons was evaluated with whole-cell patch-clamp recordings. 3× CHI ipsilateral CA1 neurons exhibited significant increases in action potential amplitude and maximum rise and decay slope while the action potential duration was decreased. Recordings of CA1 neuron postsynaptic currents were conducted to detect spontaneous excitatory and inhibitory postsynaptic currents (sEPSCs/sIPSCs) and respective miniature currents (mEPSCs and mIPSCs). In the 3× CHI mice, sEPSCs and sIPSCs in ipsilateral CA1 neurons had an increased frequency of events but decreased amplitudes. In addition, 3× CHI altered the action potential-independent miniature postsynaptic currents. The mEPSCs of ipsilateral CA1 neurons exhibited both an increased frequency of events and larger amplitudes. Moreover, the effect of 3× CHI on mIPSCs was opposite to that of the sIPSCs. Specifically, the frequency of the mIPSCs was decreased while the amplitudes were increased. These results are consistent with a mechanism in which repetitive closed-head injury affects CA1 hippocampal function by promoting a remodeling of excitatory and inhibitory synaptic inputs leading to impairment in hippocampal-dependent tasks.

Pramipexole restores depressed transmission in the ventral hippocampus following MPTP-lesion

“…Injury of visual cortex is followed by processes of enhanced neuroplasticity like LTP49. Other studies found an increase in LTP was observed after closed head injury in hippocampal CA150. These data support the view that that a compensatory mechanism for LTP or a mechanism of remodeling the neuronal networks is plausible following injury.…”

Role of Akt-independent mTORC1 and GSK3β signaling in sublethal NMDA-induced injury and the recovery of neuronal electrophysiology and survival

“…While the long-term effects of glutamate-induced excitotoxicity generally involve epileptic seizures, disruption of long-term potentiation and depression, dysregulated sEPSCs, and miniature EPSCs 48, 50, 59 , the acute effects of injury on neuronal electrophysiology are poorly characterized. In this study, we demonstrated that NMDA-induced sublethal damage causes a significant decrease in both frequency and amplitude of sEPSCs.…”

Fear learning alterations after traumatic brain injury and their role in development of posttraumatic stress symptoms

“…In animals, brain injury is associated with enhanced fear acquisition (Reger et al, 2012;Schneider et al, 2016), impaired fear extinction (Schneider et al, 2016), and altered fear circuitry (Palmer, Metheny, Elkind, & Cohen, 2016) (but see (Sierra-Mercado et al, 2015)). However, specific effects appear to depend on methods used to model brain injury (Genovese et al, 2013;Logue, Cramer, Xu, Perl, & Galdzicki, 2015;Palmer et al, 2016) and it is unclear how accurately animal models reflect TBI in humans. Improved understanding of the effects of TBI on fear learning may facilitate treatment and prevention efforts for individuals recovering from head injury.…”