Aberrant excitatory rewiring of layer V pyramidal neurons early after neocortical trauma.
Neurobiol Dis
; 91: 166-81, 2016 07.
Article
em En
| MEDLINE
| ID: mdl-26956396
ABSTRACT
Lesioned neuronal circuits form new functional connections after a traumatic brain injury (TBI). In humans and animal models, aberrant excitatory connections that form after TBI may contribute to the pathogenesis of post-traumatic epilepsy. Partial neocortical isolation ("undercut" or "UC") leads to altered neuronal circuitry and network hyperexcitability recorded in vivo and in brain slices from chronically lesioned neocortex. Recent data suggest a critical period for maladaptive excitatory circuit formation within the first 3days post UC injury (Graber and Prince 1999, 2004; Li et al. 2011, 2012b). The present study focuses on alterations in excitatory connectivity within this critical period. Immunoreactivity (IR) for growth-associated protein (GAP)-43 was increased in the UC cortex 3days after injury. Some GAP-43-expressing excitatory terminals targeted the somata of layer V pyramidal (Pyr) neurons, a domain usually innervated predominantly by inhibitory terminals. Immunocytochemical analysis of pre- and postsynaptic markers showed that putative excitatory synapses were present on somata of these neurons in UC neocortex. Excitatory postsynaptic currents from UC layer V Pyr cells displayed properties consistent with perisomatic inputs and also reflected an increase in the number of synaptic contacts. Laser scanning photostimulation (LSPS) experiments demonstrated reorganized excitatory connectivity after injury within the UC. Concurrent with these changes, spontaneous epileptiform bursts developed in UC slices. Results suggest that aberrant reorganization of excitatory connectivity contributes to early neocortical hyperexcitability in this model. The findings are relevant for understanding the pathophysiology of neocortical post-traumatic epileptogenesis and are important in terms of the timing of potential prophylactic treatments.
Palavras-chave
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Sinapses
/
Transmissão Sináptica
/
Neocórtex
/
Potenciais Pós-Sinápticos Excitadores
/
Traumatismos do Sistema Nervoso
Tipo de estudo:
Prognostic_studies
Limite:
Animals
Idioma:
En
Ano de publicação:
2016
Tipo de documento:
Article