RAPID INCREASE IN MITOCHONDRIAL VOLUME IN NUCLEUS MAGNOCELLULARIS NEURONS FOLLOWING COCHLEA REMOVAL

Second-order auditory neurons in nucleus magnocellularis (NM) of the c hick brainstem undergo a series of rapid metabolic changes following u nilateral cochlea removal, culminating in the death of 25% of NM neuro ns. Within hours of cochlea removal, ipsilateral NM neurons show marke d increases in histochemical staining for the mitochondrial enzymes su ccinate dehydrogenase and cytochrome oxidase. We investigated correspo nding ultrastructural changes in NM neurons by preparing animals under going unilateral cochlea removal for transmission electron microscopy. We quantified changes in NM mitochondrial volume by stereological met hods and qualitatively compared mitochondrial morphology between NM ne urons destined to survive and those destined to die after cochlea remo val. Within hours of cochlea removal, ipsilateral NM neurons show stri king increases in mitochondrial volume (84% at 6 hours and 236% at 12 hours after cochlea removal compared to unoperated, control animals). At 2 week survival times, ipsilateral NM neurons contain fewer mitocho ndria than contralateral neurons. Surprisingly, anesthesia alone cause s short-term increases in NM mitochondrial volume. Animals anesthetize d with pentobarbital and ketamine and sacrificed 6 or 12 hours later s howed a 45% increase in mitochondrial volume compared to previously un anesthetized animals. NM neurons destined to die within days of cochle a removal can be identified within several hours after deafferentation by the appearance of their ribosomes. We observed qualitative differe nces in mitochondrial morphology in dying neurons. Mitochondria in neu rons destined to die consistently showed mitochondrial swelling and va cuolization indicative of metabolic dysfunction. Similar mitochondrial changes have been reported when mitochondria take up excess calcium. Ultrastructural changes in NM after cochlea removal display features o f both programmed and pathological cell death, in which increased intr acellular calcium is thought to play a role. (C) 1994 Wiley-Liss, Inc.