Synaptic Strength Modulation after Cortical Trauma: A Role in Epileptogenesis

Abstract

Traumatic brain injuries are often followed by abnormal hyperexcitability, leading to acute seizures and epilepsy. Previous studies documented the rewiring capacity of neocortical neurons in response to various cortical and subcortical lesions. However, little information is available on the functional consequences of these anatomical changes after cortical trauma and the adaptation of synaptic connectivity to a decreased input produced by chronic deafferentation. In this study, we recorded intracellular (IC) activities of cortical neurons simultaneously with extracellular (EC) unit activities and field potentials of neighboring cells in cat cortex, after a large transection of the white matter underneath the suprasylvian gyrus, in acute and chronic conditions (at 2, 4, and 6 weeks) in ketamine-xylazineanesthetized cats. Using EC spikes to compute the spike-triggered averages of IC membrane potential, we found an increased connection probability and efficacy between cortical neurons weeks after cortical trauma. Inhibitory interactions showed no significant changes in the traumatized cortex compared with control. The increased synaptic efficacy was accompanied by enhanced input resistance and intrinsic excitability of cortical neurons, as well as by increased duration of silent network periods. Our electrophysiological data revealed functional consequences of previously reported anatomical changes in the injured cortex. We suggest that homeostatic synaptic plasticity compensating the decreased activity in the undercut cortex leads to an uncontrollable cortical hyperexcitability and seizure generation.

Prostaglandin E2-Induced Synaptic Plasticity in Neocortical Networks of Organotypic Slice Cultures

“…But longterm activity deprivation strengthened excitatory synapses to the extent that the hippocampal network generated seizure-like activity, revealing a potentially dark side of homeostatic regulation (Trasande and Ramirez, 2007). Indeed other reports are consistent with the notion that epileptogenesis may be an unwanted consequence of homeostatic plasticity (Houweling et al, 2005;Avramescu and Timofeev, 2008).…”

Bidirectional homeostatic plasticity induced by interneuron cell death and transplantation in vivo

“…Although the classic studies of homeostatic synaptic plasticity describe mainly increases in the amplitude of EPSCs (15), recent studies and our own data describe changes to event frequency related to both probability of presynaptic release and synapse number (16). Notably, although the phenomenon was originally described in neuronal culture systems, recent reports have described synaptic scaling in vivo following sensory deprivation (25,46) and cortical injury (47). The ability of neurons to self-regulate output levels across a range of input conditions begs the question as to whether homeostatic plasticity is a mechanism of neuroprotection during pathological states of hyperexcitability.…”

“…homeostatic changes result in reduced convergence (i.e., fewer presynaptic partners) and increased input strength onto a neuron (47). In a system requiring presynaptic synchrony to drive activity, increasing the excitatory power of each of a decreased number of presynaptic partners could raise the probability of feed-forward excitation, which could contribute to epileptogenesis.…”

Midbrain Raphe Stimulation Improves Behavioral and Anatomical Recovery from Fluid-Percussion Brain Injury

“…Regenerative mechanisms risk exuberant growth, axonal misconnection or malformation. 8,9 Released substances that are apparently injurious, on the other hand, may be essential for effective neural repair. For example, inflammatory signals can initiate the degradation of damaged tissue, allowing the replacement or removal of dysfunctional elements.…”