AXOTOMIZED NEONATAL MOTONEURONS OVEREXPRESSING THE BCL2 PROTOONCOGENERETAIN FUNCTIONAL ELECTROPHYSIOLOGICAL PROPERTIES

Bcl2 overexpression prevents axotomy-induced neuronal death of neonata l facial motoneurons, as defined by morphological criteria, However, t he functional properties of these surviving lesioned transgenic neuron s are unknown. Using transgenic mice overexpressing the protein Bcl2, we have investigated the bioelectrical properties of transgenic facial motoneurons from 7 to 20 days after neonatal unilateral axotomy using brain-stem slices and whole-cell patch-clamp recording. Nonaxotomized facial motoneurons from wild-type and transgenic mice had similar pro perties; they had an input resistance of 38 +/- 6 M Omega and fired re petitively after injection of positive current pulses. When cells were voltage-damped at or near their resting membrane potential lpha-amino -3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA), N-methyl-D-aspar tic acid (NMDA), or vasopressin generated sustained inward currents. I n transgenic axotomized mice, facial motoneurons could be found locate d ipsilaterally to the lesion; they had an input resistance of 150 +/- 30 M Omega, indicating that they were smaller in size, fired repetiti vely, and were also responsive to AMPA, NMDA, and vasopressin. Morphol ogical measurements achieved 1 week after the lesion have shown that a pplication of brain-derived neurotrophic factor prevented the reductio n in size of axotomized transgenic motoneurons. These data indicate th at Bcl2 not only prevents morphological apoptotic death of axotomized neonatal transgenic motoneurons but also permits motoneurons to conser ve functional electrophysiological properties.