Dendritic Anomalies in a Freezing Model of Microgyria: A Parametric Study

Abstract

Despite easier recognition of focal developmental cortical anomalies with modern morphological and functional imaging techniques, mechanisms leading to refractory epilepsy are still poorly understood. Recent experimental studies have shown that not only the lesioned cortex, but also the apparently normal adjacent cortex undergoes morphological changes and alterations of its neuronal connections. To further investigate the modifications of the cortex surrounding a focal maldevelopmental lesion, we applied a freezing insult to newborn rat cortex, resulting in a focal cortical malformation similar to human microgyria. Corticocortical associative neurons were retrogradely labeled in a Golgi-like fashion using biotinylated dextran amine combined with NMDA. In addition to previously reported alterations, a considerable spine loss was observed in the basal dendrites of neurons located in the eulaminated cortex adjacent to the lesion. These data demonstrate profound maldevelopmental alterations which are not limited to the macroscopically abnormal lesion, but extend at a cellular level to the surrounding cortex. The observed alterations may contribute to the increased excitability of the cortex harboring a microgyric lesion as well as the frequently associated cognitive impairment.

Enhanced Infragranular and Supragranular Synaptic Input onto Layer 5 Pyramidal Neurons in a Rat Model of Cortical Dysplasia

“…Increased recurrent excitatory connections can underlie network hyperexcitability. Longer basal dendrites are present in layer 5 corticothalamic pyramidal cells in approximately 3 months old FL rats, while layer 3 corticocortical cells have a simplified dendritic branching pattern and fewer spines (Di Rocco et al 2001. Although these studies were done in much older rats, they are in agreement with the results presented here.…”

Dendritic architecture of corticothalamic neurons in a rat model of microgyria

“…The results provided in this study, compared with those of our previous studies on layer 3 corticocortical neurons [6,9], suggest that the dendritic architecture is differently affected in different neuronal populations located in the paramicrogyric cortex. In fact, in contrast to the simplification occurring in the basal dendrites of associative neurons, layer 5 corticothalamic neurons display longer dendritic branches.…”

“…In addition, it has been observed that the generator of epileptiform activity is outside the microgyrus in the adjacent cortex [11]. We have previously demonstrated that the dendritic branching pattern of layer 3 associative neurons located in the paramicrogyric cortex is simplified and that dendritic spines are substantially reduced, possibly as a consequence of epileptogenic activity [6,9]. Here we report the dendritic architecture of corticothalamic neurons located in layer 5 of the cortex surrounding the experimentally induced lesion.…”

“…The method used to induce experimental microgyria and the retrograde tracing technique have been described in detail elsewhere [6,9]. Briefly, newborn Wistar rats (first postnatal day: P1) were each subjected to a focal lesion of the frontal cortex by applying a freezing probe over the skull surface.…”

Organization and morphology of thalamocortical neurons of mouse ventral lateral thalamus

“…We targeted physiologically confirmed regions of M1 with injections of NMDA and BDA (Jiang et al 1993; Johnson and Burkhalter 1997; Di Rocco et al 2001). This method of retrograde tracing is reliable and provides a well-defined preservation of ultra-structure, displaying organization of circuits (Jiang et al 1993; Johnson and Burkhalter 1997).…”