High-resolution 2-deoxyglucose autoradiography in quick-frozen slabs of neonatal rat olfactory bulb

We have used rapid freezing and freeze-substitution fixation to permit electron microscopic study of [3H]2-deoxyglucose autoradiographs. The techniques minimize diffusion of label into processing fluids and, by inference, migration of label within tissue. Slabs of olfactory bulbs from 12-day-old rats were quick-frozen after one hour of exposure to physiological olfactory stimuli. In light microscopic autoradiographs at low magnification, the neuropil of individual olfactory glomeruli appeared uniformly labeled with different levels of labeling in different glomeruli. At higher magnification, glomerular neuropil labeling consisted of small unlabeled regions surrounded by label clusters, suggesting greater deoxyglucose uptake by olfactory nerve terminals as compared with their postsynaptic dendrites. Periglomerular neurons were labeled differentially. Some microglia and glia precursor cells were heavily labeled in all bulbar laminae. The ultrastructure of cells and neuropil in all bulbar laminae was well-preserved. Cell processes and organelles could be identified in both stained sections and unstained electron microscopic autoradiographs. These experiments demonstrate the feasibility of combining quick-freezing with freeze substitution, in order to extend the resolution of studies using diffusable tracers such as 2-deoxyglucose. The results suggest that this is a promising method for assessing several controversies concerning deoxyglucose incorporation and neuronal and glial metabolism.

[1]  Telford Jn The expandable loop: an improved wire-loop device for producing thin photographic films suited to autoradiographic electron microscopy. , 1969 .

[2]  P. Witkovsky,et al.  Uptake and localization of 3H‐2 deoxy‐D‐glucose by retinal photoreceptors , 1982, The Journal of comparative neurology.

[3]  A. W. Rogers Techniques of autoradiography , 1967 .

[4]  N. Blackett,et al.  A simplified method of "hypothetical grain" analysis of electron microscope autoradiographs. , 1977, The journal of histochemistry and cytochemistry : official journal of the Histochemistry Society.

[5]  E. Buchner,et al.  Functional neuroanatomical mapping in insects by [3H]2-deoxy-D-glucose at electron microscopical resolution , 1982, Neuroscience Letters.

[6]  P. Greengard,et al.  Metabolism and Function in Nerve Fibers , 1971 .

[7]  B. J. Rooney,et al.  2-Deoxyglucose uptake and histologic changes in rat thalamus after neocortical ablations , 1984, Experimental Neurology.

[8]  F. Sharp Relative cerebral glucose uptake of neuronal perikarya and neuropil determined with 2-deoxyglucose in resting and swimming rat , 1976, Brain Research.

[9]  Martin H. Teicher,et al.  Functional development of the olfactory bulb and a unique glomerular complex in the neonatal rat , 1982, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[10]  M. A. Matthews,et al.  Electron microscopy of non‐neuronal cellular changes accompanying neural degeneration in thalamic nuclei of the rabbit. II. Reactive elements within the neuropil , 1973, The Journal of comparative neurology.

[11]  J S Kauer,et al.  Mapping of odor-related neuronal activity in the olfactory bulb by high-resolution 2-deoxyglucose autoradiography. , 1982, Proceedings of the National Academy of Sciences of the United States of America.

[12]  H. Plattner,et al.  Cryofixation: a tool in biological ultrastructural research. , 1982, International review of cytology.

[13]  M. Reivich,et al.  THE [14C]DEOXYGLUCOSE METHOD FOR THE MEASUREMENT OF LOCAL CEREBRAL GLUCOSE UTILIZATION: THEORY, PROCEDURE, AND NORMAL VALUES IN THE CONSCIOUS AND ANESTHETIZED ALBINO RAT 1 , 1977, Journal of neurochemistry.

[14]  S. Basinger,et al.  Differential labelling of retinal neurones by 3H-2-deoxyglucose , 1979, Nature.

[15]  C. P. Leblond,et al.  Investigation of glial cells in semithin sections. I. Identification of glial cells in the brain of young rats , 1973, The Journal of comparative neurology.

[16]  R. Lindsay,et al.  Schwann cells of the olfactory nerves contain glial fibrillary acidic protein and resemble astrocytes , 1982, Neuroscience.

[17]  L. Sokoloff,et al.  Computerized densitometry and color coding of [14C] deoxyglucose autoradiographs , 1980, Annals of neurology.

[18]  T M Mayhew,et al.  Stereological approach to the study of synapse morphometry with particular regard to estimating number in a volume and on a surface , 1979, Journal of neurocytology.

[19]  A. van Harreveld,et al.  Electron microscopy after rapid freezing on a metal surface and substitution fixation , 1964, The Anatomical record.

[20]  Methods for 3H-2-D-deoxyglucose autoradiography on film and fine-grain emulsions. , 1980, Stain technology.

[21]  J. E. Vaughn,et al.  The morphology and development of neuroglial cells. , 1971, UCLA forum in medical sciences.

[22]  R. C. Collins Use of cortical circuits during focal penicillin seizures: An autoradiographic study with [14C]deoxyglucose , 1978, Brain Research.

[23]  Martin H. Teicher,et al.  Suckling pheromone stimulation of a modified glomerular region in the developing rat olfactory bulb revealed by the 2-deoxyglucose method , 1980, Brain Research.

[24]  J. Mcculloch,et al.  A potential error in modifications of the [14C]2-deoxyglucose technique , 1983, Brain Research.

[25]  T. Powell,et al.  The neuropil of the glomeruli of the olfactory bulb. , 1971, Journal of cell science.

[26]  A. Gelperin,et al.  Localization of [3H]-2-deoxy glucose in single molluscan neurones , 1980, Nature.

[27]  F. Sharp,et al.  Localization of [3H]2-deoxyglucose at the cellular level using freeze-dried tissue and dry-looped emulsion , 1982, Brain Research.

[28]  F R Sharp,et al.  Laminar analysis of 2-deoxyglucose uptake in olfactory bulb and olfactory cortex of rabbit and rat. , 1977, Journal of neurophysiology.

[29]  T. Woolsey,et al.  Cellular localization of 2-[3H]deoxy-D-glucose from paraffin-embedded brains , 1981, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[30]  A. Miller,et al.  Loss of radioactive 2-deoxy-d-glucose-6-phosphate from brains of conscious rats: Implications for quantitative autoradiographic determination of regional glucose utilization , 1978, Neuroscience.

[31]  C. Pilgrim,et al.  A system of cells in the unstimulated rat brain characterized by preferential accumulation of [3H]deoxyglucose , 1979, Neuroscience Letters.

[32]  C. P. Leblond,et al.  Investigation of glial cells in semithin sections. III. Transformation of subependymal cells into glial cells, as shown by radioautography after 3H‐thymidine injection into the lateral ventricle of the brain of young rats , 1973, The Journal of comparative neurology.

[33]  M. Salpeter,et al.  Resolution of electron microscope autoradiography. IV. Application to analysis of autoradiographs , 1978, The Journal of cell biology.

[34]  A. Privat Postnatal gliogenesis in the mammalian brain. , 1975, International review of cytology.

[35]  V. Pentreath,et al.  High resolution analysis of [3H]2-deoxyglucose incorporation into neurons and glial cells in invertebrate ganglia: Histological processing of nervous tissue for selective marking of glycogen , 1981, Journal of neurocytology.

[36]  G. Shepherd,et al.  Functional organization of rat olfactory bulb analysed by the 2‐deoxyglucose method , 1979, The Journal of comparative neurology.

[37]  C. Stirling,et al.  HIGH-RESOLUTION RADIOAUTOGRAPHY OF GALACTOSE-3H ACCUMULATION IN RINGS OF HAMSTER INTESTINE , 1967, The Journal of cell biology.

[38]  T. Powell,et al.  The neuron types of the glomerular layer of the olfactory bulb. , 1971, Journal of cell science.

[39]  Sanford L. Palay,et al.  The fine structure of the nervous system: The neurons and supporting cells , 1976 .

[40]  H. Gundersen,et al.  Notes on the estimation of the numerical density of arbitrary profiles: the edge effect , 1977 .

[41]  T. Reese,et al.  Preservation of synaptic structure by rapid freezing. , 1976, Cold Spring Harbor symposia on quantitative biology.