Rapid increase in mitochondrial volume in nucleus magnocellularis neurons following cochlea removal

Abstract

Second-order auditory neurons in nucleus magnocellularis (NM) of the chick brainstem undergo a series of rapid metabolic changes following unilateral cochlea removal, culminating in the death of 25% of NM neurons. Within hours of cochlea removal, ipsilateral NM neurons show marked increases in histochemical staining for the mitochondrial enzymes succinate dehydrogenase and cytochrome oxidase. We investigated corresponding ultrastructural changes in NM neurons by preparing animals undergoing unilateral cochlea removal for transmission electron microscopy. We quantified changes in NM mitochondrial volume by stereological methods and qualitatively compared mitochondrial morphology between NM neurons destined to survive and those destined to die after cochlea removal. Within hours of cochlea removal, ipsilateral NM neurons show striking 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 mitochondria than contralateral neurons. Surprisingly, anesthesia alone causes short-term increases in NM mitochondrial volume. Animals anesthetized with pentobarbital and ketamine and sacrificed 6 or 12 hours later showed a 45% increase in mitochondrial volume compared to previously unanesthetized animals. NM neurons destined to die within days of cochlea removal can be identified within several hours after deafferentation by the appearance of their ribosomes. We observed qualitative differences in mitochondrial morphology in dying neurons. Mitochondria in neurons destined to die consistently showed mitochondrial swelling and vacuolization 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 of both programmed and pathological cell death, in which increased intracellular calcium is thought to play a role.

Increased deafferentation-induced cell death in chick brainstem auditory neurons following blockade of mitochondrial protein synthesis with chloramphenicol

“…Cel l Death i n NM transmission electron microscopy that these initial increases in wa et al, 1987). The activity of these oxidative enzymes can be oxidative capacity are mediated in large part by an increase in mitochondrial volume in NM neurons (Hyde and Durham, 1993).…”

Ear manipulations reveal a critical period for survival and dendritic development at the single‐cell level in Mauthner neurons

“…Therefore, it is also possible that these additional inputs stabilize the vestibular nucleus. Comparable to age related differential cell death (Lopez‐Otin et al, ), the causality for survival of some and death of other second‐order neurons following deafferentation remains unclear (Durham and Rubel, ; Steward and Rubel, ; Born and Rubel, ; Durham et al, ; Garden et al, ; Hyde and Durham, ,b; Garden et al, ; Kelley et al, )…”

Conductive Hearing Loss Results in Changes in Cytochrome Oxidase Activity in Gerbil Central Auditory System

“…There is some evidence that normal environmental sounds, including variations in patterns of auditory It is difficult to explain why CHL might result in an increase rather than a decrease (as in CA) in the stimulation, are necessary for normal development of the CAS (Sanes and Constantine-Paton 1985a, b; Keillength of the MSO dendrites. It should be noted that the apparent increase in length could also reflect an mann and Herdegen 1997; Ryugo et al 1998). increase in CO density in the more distal portions of the dendrites; our method of analysis would not differentiate between these two possibilities.…”

“…Single-unit responses in the ventral cochlear nucleus (VCN) are adultlike by P18 Suction was used to aspirate cochlear fluid and membranous components. The wound was then closed with but auditory responses continue to mature until at least P30 (Ryan 1976;Woolf andRyan 1984, 1985). suture or cyanoacrylate glue.…”

“…Brains were notched at the right cerebellum, and transverse sections through the brainstem auditory nuclei were cut at 16-m thickness on a cryostat at Ϫ21ЊC. A one-in-four series of sections was rapidly thaw-mounted onto Superfrost Plus slides (Fisher Scientific, St. Louis, MO), air dried for at least 30 minutes, and then processed within 6 hours of sectioning using an established CO protocol (Hyde and Durham 1990). Slides were incubated at 37ЊC in a staining solution which contained, per 100 mL, the following: 50 mg diaminobenzidine, 20 mg cytochrome C, type III (Sigma Chemical Co., St. Louis, MO, USA), and 4 g sucrose in 0.1 M phosphate buffer (PB) at pH 7.4.…”