Axonal sprouting in layer V pyramidal neurons of chronically injured cerebral cortex

Abstract

We performed experiments to determine whether axonal sprouting occurs in neurons of chronic neocortical epileptogenic lesions. Partially isolated somatosensory cortical islands with intact pial blood supply were prepared in mature rats. Neocortical slices from these lesions, studied 6-39 d later, generated spontaneous and/or evoked epileptiform field potentials (Prince and Tseng, 1993) during which neurons displayed prolonged polyphasic excitatory and inhibitory synaptic potentials/currents. Single electrophysiologically characterized layer V pyramidal neurons in control and epileptogenic slices were filled with biocytin using sharp and patch-electrode techniques, their axonal arbors reconstructed and compared quantitatively. Neurons in injured cortex had a 56% increase in total axonal length, a 64% increase in the number of axonal collaterals and more than a doubling (115% increase) of the number of axonal swellings. The presumed boutons were smaller and more closely spaced than those of control cells. In some neurons the main descending axon had hypertrophic segments from which branches arose. These highly significant changes were most marked in the perisomatic region of layer V. The axonal sprouting was associated with a decrease in somatic area but no significant change in dendritic arbors. Results suggest that a significant degree of axonal reorganization takes place in the chronically injured cortex where it might be an adaptive mechanism for recovery of function after injury, or might be maladaptive and play an important role in the generation of epileptiform events by increasing the numbers and density of synaptic contacts between neurons.

Synaptic Strength Modulation after Cortical Trauma: A Role in Epileptogenesis

“…Here, we show physiological consequences of axonal sprouting accompanying posttraumatic epileptogenesis (Salin et al, 1995).…”

“…The brain restores its activity after injury by extensive reorganization of cortical connectivity, such as axonal sprouting with formation of new synapses (Purpura and Housepian, 1961;Sutula et al, 1989;Salin et al, 1995;Dancause et al, 2005); by selective loss of inhibitory synapses (Ribak and Reiffenstein, 1982); or by increased synaptic and intrinsic neuronal responsiveness (Bush et al, 1999).…”

“…The undercut cortex becomes increasingly hyperexcitable over a few weeks and progressively generates paroxysmal activity, both in vivo (Nita et al, 2006(Nita et al, , 2007 and in vitro (Prince and Tseng, 1993;Salin et al, 1995). Several mechanisms may contribute to the development of hyperexcitability after cortical injury, including changes in intrinsic neuronal properties (Esplin et al, 1994;Topolnik et al, 2003a), selective loss of inhibitory synapses (Ribak and Reiffenstein, 1982), increase of both inhibition and excitation (Bush et al, 1999), and axonal sprouting (Salin et al, 1995).…”

Enhanced Excitatory Synaptic Connectivity in Layer V Pyramidal Neurons of Chronically Injured Epileptogenic Neocortex in Rats

“…Neuronal injuries after cortical trauma, stroke, and prolonged seizures result in axonal sprouting in the hippocampus and neocortex (Tauck and Nadler, 1985;Salin et al, 1995;Perez et al, 1996;Sutula et al, 1998;Esclapez et al, 1999;Golarai et al, 2001;Santhakumar et al, 2001;Buckmaster et al, 2002;Marchenko et al, 2004). This process may underlie the capacity of neuronal circuits to recover from damage (Stroemer et al, 1998;Carmichael et al, 2001;Carmichael, 2003;Lee et al, 2004); however, formation of new excitatory circuitry may also contribute to pathophysiological processes such as epileptogenesis (Purpura and Housepian, 1961;Sutula et al, 1992;Dudek and Spitz, 1997;McKinney et al, 1997;Prince et al, 1997;Prince, 1999).…”

Recurrent Circuits in Layer II of Medial Entorhinal Cortex in a Model of Temporal Lobe Epilepsy

“…Synaptic reorganization is another potential mechanism of hyperexcitability of layer II stellate cells. Many types of neurons display aberrant axon sprouting and synaptogenesis in epilepsy models (Nadler et al, 1980;Salin et al, 1995;Perez et al, 1996;McKinney et al, 1997), raising the possibility of recurrent excitatory synapses in the entorhinal cortex in patients and models of temporal lobe epilepsy. Analogous to loss of hilar neurons and sprouting of granule cell axons in the dentate gyrus (Nadler et al, 1980), loss of layer III neurons in the medial entorhinal cortex, which normally projects axons superficially (Köhler, 1986) and synapses with dendritic spines (Germroth et al, 1991), might trigger or permit development of aberrant recurrent excitatory synapses among layer II stellate cells.…”