Frank R. Sharp

Functional ontogeny in the central auditory pathway of the mongolian gerbil - A 2-deoxyglucose study

SummaryThe 2-deoxyglucose (2-DG) autoradiographic technique was used to map functional activity in the central auditory system of the mongolian gerbil, throughout the period of functional onset. Uptake of 2-DG during exposure to 105 dB SPL wide band noise (WBN) was compared to silence in adults and in neonates at 12, 14, 16 and 18 days after birth (DAB). At 12 DAB, WBN exposure increased 2-DG uptake relative to silence only in the ventral cochlear nucleus. At 14 DAB, 2-DG uptake increased during WBN in the entire cochlear nuclear complex, superior olivary complex, and ventral nucleus of the lateral lemniscus. These stimulus-evoked increases in 2-DG uptake were at adult levels. However, little or no stimulus-evoked increase was seen in higher auditory nuclei at 14 DAB. By 16 DAB, 2-DG uptake also increased during WBN exposure in the dorsal nucleus of the lateral lemniscus, inferior colliculus and medial geniculate nucleus. By 18 DAB, WBN exposure produced increases in 2-DG uptake of medullary and pontine auditory nuclei which exceeded those seen in adults. At higher levels of the pathway, increases were comparable to those seen in adults. WBN-induced increases in 2-DG uptake observed in the cochlear nuclear and superior olivary complexes of neonates were comparable in all regions at all ages, even at 12 DAB. However, the 2-DG uptake increases observed at 16 and 18 DAB were appreciably greater in those regions of the inferior colliculus and medial geniculate nucleus which respond to high frequencies.

Increasing intensities of wide band noise increase [14C]2-deoxyglucose uptake in gerbil central auditory structures

The [14C]2-deoxyglucose (2DG) technique has been used to map the effects of increasing intensities of wide band noise on 2DG uptake in mongolian gerbil brain auditory structures. Animals were injected with [14C]2DG and exposed to silence or continuous wide band noise at 25 dB, 45 dB, 65 dB, 85 dB or 105 dB SPL. Brains were removed, frozen-sectioned and autoradiographed on X-ray film. The ratio of the optical density of gray matter structures to the optical density of cerebellar peduncles in each animal was used to semiquantitate the results. The dorsal and ventral cochlear nuclei, superior olive/trapezoid body, inferior colliculus, and the dorsal and ventral nuclei of the lateral lemniscus all showed increases in 2DG uptake during exposure to wide band noise (WBN). As noise intensity increased from 0 to 105 dB SPL, 2DG uptake increased regularly to a maximum at 85 or 105 dB SPL. As WBN intensity increased, deeper layers of inferior colliculus were activated. The medial geniculate nucleus and auditory cortex showed a lesser increase in 2DG uptake during noise exposure. Non-auditory structures, including the cerebellar cortex and the medullary reticular nuclei, showed no increase in 2DG uptake during noise exposure at any intensity tested.

Auditory stimulation alters the pattern of 2-deoxyglucose uptake in the inner ear

The 2-deoxy-D-glucose (2-DG) autoradiographic technique was adapted for application to the inner ear. The uptake of [14C]-DG during silence was compared with that observed during exposure to wide band noise (WBN) or pure tones at an intensity level of 85 db SPL. In silence, the highest levels of 2-DG uptake were observed in the spiral ligament, spiral prominence and stria vascularis, with approximately equal levels of uptake in each structure. The high levels of 2-DG uptake observed in the ligament and prominence are surprising, and suggest a more active role for these structures in cochlear function than has previously been suspected. Levels of uptake in the organ of Corti, spiral ganglion and VIIIth nerve were much lower, although well above background. During exposure to WBN, 2-DG uptake increased markedly in the VIIIth nerve, and spiral ganglion throughout the cochlea, and in the organ of Corti in the lower basal turn. 2-DG uptake did not change significantly in the spiral ligament or stria vascularis. During pure tone exposure, increased 2-DG uptake was noted in localized regions of the VIIIth nerve and spiral ganglion.

Thiamine Deficiency Limits Glucose Utilization and Glial Proliferation in Brain Lesions of Symptomatic Rats

The effects of thiamine (B1) deficiency on local CMRglu (LMCRglu) in the vestibular nuclei were studied with the 14C-2-deoxyglucose autoradiographic method in awake asymptomatic and symptomatic rats. Animals on the B1-deficient diet for 98 days developed symptoms of ataxia and opisthotonos. The results show that B1 deficiency produces: (1) bilateral vestibular nuclei lesions in symptomatic animals; (2) very low LCMRglu rates in these lesions; and (3) limitation of glial proliferation in the lesions. Giving B1 to B1-deficient symptomatic animals produced a cellular proliferative response consisting mostly of microglia in the lesioned areas of the vestibular nuclei and a high LCMRglu rate in the regions of microglial proliferation.

Relative 2-deoxyglucose uptake of the paratrigeminal nucleus increases during hibernation

The paratrigeminal nucleus, a little-studied cell group of the medulla, is the only structure of the brain to significantly increase its relative [14C]2-deoxyglucose accumulation during hibernation in the ground squirrel. The zone of increased activity on the auto-radiographs is continuous between this structure and the marginal zone of the spinal trigeminal nucleus. Because of the known thermoafferent function of the latter structure, a similar function is suggested for the paratrigeminal nucleus.

Bilateral [14C]2-deoxyglucose uptake by motor pathways after unilateral neonatal cortex lesions in the rat

The left sensorimotor (SM) cortex was removed in 1-day-old and 30-day-old rats. At 90 days of age [14C]2-deoxyglucose (2DG) was injected and the right motor (MI) cortex was electrically stimulated to produce predominantly left vibrissae movements. Animals were sacrificed and their brains autoradiographed. Right motor cortex (MI) stimulation activated subcortical structures bilaterally in 3 of 5 neonatally lesioned rats. Right MI stimulation activated most subcortical structures unilaterally in 30-day lesioned rats. This implies that a critical period for SM cortex injury may occur between 1 and 30 days of age. We suggest that removal of left SM cortex at 1 day of age occurs before or during the critical period and this induces right MI cortex to form bilateral subcortical connections. The bilateral 2DG uptake increases imply the bilateral connections are functional. The unilateral subcortical activation in 2 of 5 neonatally lesioned animals may have been due to differences in size of the lesion, parameters of stimulation, or perhaps due to the time of the lesion being near the critical period. We also suggest that removal of left SM cortex at 30 days of age occurs after the critical period, but that this does not affect the predominantly ipsilateral subcortical connections from MI cortex which have previously formed during normal development.

Increased subcortical and laminar cortical 2-deoxy[14C]glucose uptake during cerebellar stimulation.

Abstract 2-Deoxy[ 14 C]glucose (2DG) uptake was mapped in brains of conscious rats during cerebellar hemisphere electrical stimulation and compared with sham-operated controls. The 2DG uptake increased bilaterally in cerebellar cortex and deep nuclei, the largest increases being ipsilateral to the stimulating electrode. Structures which increased 2DG uptake bilaterally but had larger contralateral increases included the red nucleus, inferior olive, zona incerta, substantia nigra, globus pallidus, deep mesencephalic nucleus, habenula, reticular tegmental nucleus of the pons, ventroanterolateral and ventromedial nuclei of thalamus, several other thalamic nuclei, and motor-somatosensory cortex. Most of these structures receive efferent fibers from cerebellar nuclei. Cerebellar stimulation produced two bands of 2DG uptake bilaterally in rat motor-somatosensory neocortical laminae IV and Vc-VIa. Shamoperated controls had one band of 2DG uptake in neocortical lamina IV. We postulate that cerebellar stimulation increased 2DG uptake polysynaptically in lamina Vc-VIa by the following pathway: Purkinje cells → deep cerebellar nuclei → ventrolateral and/or ventromedial nuclei of thalamus → lamina Vc-VIa of neocortex. Activation of these cortical laminae could affect cortical seizure foci.

Metabolic activation of the brachium conjunctivum during induced hypothermia.

During hypothermia induced in ground squirrels by the halothane-heliox method, 2-deoxyglucose uptake of a white matter structure, the brachium conjunctivum, increased relative to the surrounding gray matter structures. The possibility of 2-deoxyglucose uptake by glial as well as neuronal elements in the brachium conjunctivum and the implications of this observation for the use of optical density ratios is discussed.

Autoradiographic patterns of hippocampal metabolism during induced hypothermia.

[14C]2-Deoxyglucose (2-DG) uptake in the hippocampal formation was studied in the ground squirrel subjected to induced hypothermia. Whereas the stratum lacunosum-molecular has the highest 2-DG uptake in the dorsal hippocampus during euthermia, 2-DG uptake in the stratum lacunosum-molecular and stratum radiatum are similar during hypothermia. This may indicate activation of a cholinergic input to the hippocampus during hypothermia.