The Inferior Colliculus

The Inferior Colliculus

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Posted:  April 24, 2000 08:01 PM
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Eileen Nicole Simon

Blood flow | Deoxy-glucose uptake | Other Measures
Functional significance of high aerobic metabolism | Vulnerability
References
Blood Flow in the Brain

Measurements of blood flow in the brain have revealed the highest levels in the inferior colliculus. The table below is from Landau et al. (1955), in which distribution of a radioactive tracer was measured one minute after injection in cats. These researchers at first attributed the high levels in auditory structures to be due to noise of the equipment they were using, but repeated their experiments with deafened cats and found the same pattern of distribution.

Fisch (1970) questioned whether finding nuclei of the auditory system to be metabolically the most active should have been a surprise. He pointed out that hearing functions all the time, even while we sleep, and that hearing is the sense that continuously keeps us in touch with the environment around us. Fisch cited the research of Craigie (1920, 1938) who used India ink injections to investigate vascularity in the brain, and found the greatest capillary supply to brainstem auditory nuclei.

Cerebral Blood Flow in Cats
Brain Structurecc/gm/minBrain System
Inferior colliculus1.80auditory
Sensory-motor cortex1.38
Auditory cortex1.30
Visual cortex1.25
Medial geniculate1.22auditory
Lateral geniculate1.21visual
Superior colliculus1.15visual
Caudate1.10subcortical motor
Thalamus1.03
Association cortex0.88
Cerebellar nuclei0.87
Cerebellar white matter0.24
Cerebral white matter0.23
Spinal cord white matter0.14
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Glucose utilization

Sokoloff et al. (1977) substituted carbon-14 labeled deoxyglucose for the inert tracer used by Landau et al. (1955) to measure blood flow. Deoxyglucose is an analogue of glucose that enters the brain but then is not further metabolized. Uptake of deoxyglucose provides a measure of glucose utilization that can differ from blood flow in some circumstances. Normally glucose uptake is greatest in the same brain areas with the highest rate of circulation. Baseline values for blood flow and deoxyglucose uptake can both be used as estimates of metabolic rate, and these methods are now revealing more and more the often surprising effects of drugs and other factors that alter homeostasis in the brain.

The table below is adapted from data presented by Sokoloff (1981). As in the measurements of blood flow, baseline uptake of deoxyglucose is highest in the inferior colliculus. Sokoloff remarked that "the inferior colliculus is clearly the most metabolically active structure in the brain."

Deoxyglucose Uptake
Brain StructureMonkeyAlbino RatBrain System

SD 1-4SD 2-7
Inferior colliculus103197auditory
Auditory cortex79162
Vestibular nucleus66128
Medial geniculate65131auditory
Superior olivary nucleus63133auditory
Visual cortex59107
Mammillary body57121limbic
Superior colliculus5595auditory
Thalamus, lateral nucleus54116
Caudate-putamen52110subcortical motor
Cochlear nucleus51113auditory
Cerebellar nuclei45100
Sensorimotor cortex44120
Lateral geniculate3996visual
Hippocampus3979limbic
Cerebellar cortex3157
Cerebellar white matter1237
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Other Measures of High Aerobic Metabolism

High levels of glucose transport proteins and enzymes that drive aerobic metabolism match high blood flow and deoxyglucose uptake in the inferior colliculus. The table below (adapted from Zeller et al., 1997) shows that glucose transport protein (GLUT1) and capillary density are also highest in the inferior colliculus of laboratory rats.

GLUT1 and Capillary Density in Rats
Brain StructureGLUT1 DensityCapillary DensityBrain System

SD 31-109SD 19-108
Inferior colliculus652433auditory
Posterior cortex603401
Frontal cortex586365
Superior colliculus554309visual
Visual cortex548327
Anterior olfactory nucleus528227smell
Medial Geniculate body519303auditory
Hippocampus CA1 region 484230limbic
Caudate nucleus462287subcortical motor
Auditory cortex397216
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Functional Significance of High Aerobic Metabolism

The especially high metabolic rate in the inferior colliculus must support some essential function. Processing of acoustic stimuli in the inferior colliculus plays a key role in representation of space, and this involves moment to moment damping of some signals to enhance focus on sounds of greater importance. Inhibitory as well as excitatory neurotransmitters appear to work together in the inferior colliculi to provide functions such as detection of sound onset with a damping function to prevent persistent stimulation (Faingold et al. 1991, Zhang & Feng 1998).

The hypersensitivity to sounds displayed by some autistic children may represent loss of inhibitory function. Inability to distinguish sound onset then relegate it to background awareness could also be part of the difficulty in recognizing boundaries between words and syllables in spoken language.

Caspary et al. (1995) provided data showing decline with advancing age of neurotransmitter function in the inferior colliculus that may lead to loss of the capacity to detect and extract meaningful signals from background noise. They pointed out that this leads to difficulty following a conversation in a noisy environment and may be the reason some elderly people withdraw from participation in society. The same or similar disability may lead children with autism to avoid social contact.

Lack of social responsiveness and disinterest in communication are thought by many researchers to be the primary problem of children with autism. But any factor that diminishes the high rate of activity within the auditory system may decrease environmental awareness.

Jane et al. (1965) described loss of attention and behavioral changes in cats after severing the brachium of the inferior colliculus (its connection to the thalamus). Sprague et al. (1961) likewise observed a dramatic loss of attention, affect, and motivation in cats after severing the lateral lemniscal tracts between the superior olive and inferior colliculus. They commented that these behavior changes were reminiscent of autistic children, and compared their findings with those of Klver and Bucy (1939) who obtained similar behavioral deficits after removing the temporal lobes of monkeys.

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Denny-Brown (1962) also described profound losses of awareness, responsiveness, and drive in monkeys after ablation of the superior (visual) colliculi. He proposed that this might be the most essential structure for unitary function of the brain. Denny-Brown may have also removed portions of the inferior colliculi, or their connections with the superior colliculi in his experiments.

Hearing is an accessory to vision in the species familiar to most of us because the auditory system is the most recent evolutionary extension of senses that provide environmental awareness. We turn our heads and look for things that make noises but rarely try to hear something that happens to pass by our field of vision.

The auditory system likely has more work to do and thus requires more energy than if it evolved without any relationship to other sensory systems.


Vulnerability

The brainstem nuclei of high metabolic rate are vulnerable to anoxia and toxic substances that disrupt function of the aerobic enzymes. A distinctive pattern of brainstem damage known as Wernicke's encephalopathy is observed in cases of alcohol intoxication or exposure to poisonous substances such as lead, mercury, and toxic fumes.

Wernicke's encephalopathy is also caused by vitamin B1 (thiamine) deficiency; this vitamin is an essential co-enzyme for aerobic enzymes. A disease known as beriberi became common in the early twentieth century in areas of the world such as Japan in which refined white rice replaced brown rice as a dietary staple. The idea that brain damage in alcoholism is caused by thiamine deficiency is based on the assumption that loss of interest in food leads to under-nutrition. But alcohol is probably also directly toxic to aerobic enzymes.

Cardiac arrest and asphyxia also lead to brainstem damage in a pattern similar to Wernicke's encephalopathy, as do some infections of the brain. Variability in which of the brainstem nuclei of high metabolic rate are damaged is likely due to a variety of protective biofeedback mechanisms, and the most active inferior colliculus may have priority over areas with lesser metabolic demands. Thus the mammillary bodies are most prominently affected in Wernicke's encephalopathy but in acute thiamine deficiency, or poisoning with chemicals like pyrithiamine, the inferior colliculus is the most vulnerable.

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References

Metabolic measures | Functional signifigance | Vulnerability

Blood flow, deoxyglucose uptake, and other measures of aerobic activity

Chugani HT, Hovda DA, Villablanca JR, Phelps ME, Xu, W-F (1991) Metabolic maturation of the brain: a study of local cerebral glucose utilization in the developing cat. Journal of Cerebral Blood Flow and Metabolism 11:35-47.

Craigie EH (1920). On the relative vascularity of various parts of the central nervous system of the albino rat. Journal of Comparative Neurology, 31, 429-464.

Craigie EH (1938). Vascularity in the brain of the frog (Rana Pipiens). Journal of Comparative Neurology, 69, 453-479.

Fisch L (1970) The selective and differential vulnerability of the auditory system. In GEW Wolstenholm and J Knight, (Eds), Sensorineural Hearing Loss: A Ciba Foundation Symposium (pp 101-116). London: Churchill.

Gonzalez-Lima F, Valla J, Matos-Collazo S (1997) Quantitative cytochemistry of cytochrome oxidase and cellular morphometry of the human inferior colliculus in control and Alzheimer's patients. Brain Research 752:117-126.

Hovda DA, Villablanca JR, Chugani HT, Phelps ME (1996) Cerebral metabolism following neonatal or adult hemineodecortication in cats: I. effects on glucose metabolism using [14C]2-deoxy-D-glucose autoradiography. Journal of Cerebral Blood Flow and Metabolism 16:134-146.

Hovda DA, Chugani HT, Villablanca JR, Badie B, Sutton RL (1992) Maturation of cerebral oxidative metabolism in the cat: a cytochrome oxidase histochemistry study. Journal of Cerebral Blood Flow and Metabolism 12:1039-1048.

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Landau WM, Freygang WH, Rowland LP, Sokoloff L, Kety SS (1955) The local circulation of the living brain; values in the unanesthetized and anesthetized cat. Transactions of the American Neurological Association 80:125-129.

Rahner-Welsch S, Vogel J, Kuschinsky, W (1995) Regional congruence and divergence of glucose transporters (GLUT1) and capillaries in rat brains. Journal of Cerebral Blood Flow and Metabolism 15:681-686.

Sokoloff L (1981) Localization of functional activity in the central nervous system by measurement of glucose utilization with radioactive deoxyglucose. Journal of Cerebral Blood Flow and Metabolism 1:7-36.

Sokoloff L, Reivich M, Kennedy C, Des Rosiers MH, Patlak CS, Pettigrew KD, Sakurada O, Shinohara M (1977) The [14C]deoxyglucose method for the measurement of local cerebral glucose utilization: theory, procedure, and normal values in the conscious and anesthetized albino rat. Journal of Neurochemistry 28:897-916.

Zeller K, Rahner-Welsch S, Kuschinsky W (1997) Distribution of Glut1 glucose transporters in different brain structures compared to glucose utilization and capillary density of adult rat brains. Journal of Cerebral Blood Flow and Metabolism 17:204-209.

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Functional Significance

Caspary DM, Milbrandt JC, Helfert RH (1995) Central auditory aging: GABA changes in the inferior colliculus. Experimental Gerontology 30:349-360.

Denny-Brown D (1962) The midbrain and motor integration. Proceedings of the Royal Society of Medicine 55:527-538.

Faingold CL, Gehlbach G, Caspary DM (1991) Functional pharmacology of inferior coliculus neurons. In R.A. Altschuler et al. Neurobiology of Hearing: The Central Auditory System. New York: Raven Press, pp 223-252 (chapter 10).

Jane JA, Masterton RB, Diamond IT (1965) The function of the tectum for attention to auditory stimuli in the cat. Journal of Comparative Neurology 125:165-192.

Kluver H & Bucy PC (1939) Preliminary analysis of functions of the temporal lobes in monkeys. Archives of Neurology and Psychiatry 42:979-1000.

Sprague JM, Chambers WW, Stellar, E (1961) Attentive, affective, and adaptive behavior in the cat. Science 133:165-173.

Zhang H, Feng AS (1998) Sound direction modifies the inhibitory as well as the excitatory frequency tuning characteristics of single neurons in the frog torus semicircularis (inferior colliculus). J Comp Physiol [A] 1998 Jun;182(6):725-735

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Vulnerability

Bertoni JM and Sprenkle PM (1989) Lead acutely reduces glucose utilization in the rat brain especially in higher auditory centers. Neurotoxicology 9:235-242.

Bini L and Bollea G (1947). Fatal poisoning by lead-benzine (a clinico-pathologic study). Journal of Neuropathology and Experimental Neurology 6:271-285.

Bodian D (1949) Histopathologic basis of clinical findings in poliomyelitis. American Journal of Medicine 6:563-578.

Burchfield DJ, Abrams RM (1993). Cocaine depresses cerebral glucose utilization in fetal sheep. Developmental Brain Research 73:283-288.

Calingasan NY, Baker H, Sheu KF, Gibson GE (1994) Distribution of the alpha-ketoglutarate dehydrogenase complex in rat brain. Journal Of Comparative Neurology 346:461-479.

Call RA and Gunn FD (1949) Arsenical encephalopathy. Archives of Pathology 48:119-128.

Cavanagh JB (1992) Methyl bromide intoxication and acute energy deprivation syndromes. Neuropathology and Applied Neurobiology 18:575-578.

Cavanagh JB, Nolan CC (1993) The neurotoxicity of alpha-chlorohydrin in rats and mice: II. Lesion topography and factors in selective vulnerability in acute energy deprivation syndromes. Neuropathology and Applied Neurobiology 19:471-479.

Chen Q, Okada S, Okeda R (1997) Causality of parenchymal and vascular changes in rats with experimental thiamine deficiency encephalopathy. Pathology International 47:748-756

D'Aprile P, Gentile MA, Carella A (1994) Enhanced MR in the acute phase of Wernicke encephalopathy. AJNR. American Journal Of Neuroradiology 15:591-593.

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d'Avella D, Cicciarello R, Gagliardi ME, Albiero F, Mesiti M, Russi E, D'Aquino A, Tomasello F (1994) Progressive perturbations in cerebral energy metabolism after experimental whole-brain radiation in the therapeutic range. Journal of Neurosurgery 81:774-779.

d'Avella D, Cicciarello R, Zuccarello M, Albiero F, Romano A, Angileri FF, Salpietro FM, Tomasello F (1996) Brain energy metabolism in the acute stage of experimental subarachnoid haemorrhage: local changes in cerebral glucose utilization. Acta Neurochir (Wien) 138:737-743.

Dow-Edwards DL, Freed LA, Fico TA (1990) Structural and functional effects of prenatal cocaine exposure in adult rat brain. Brain Research Developmental Brain Research 57:263-268.

Dreyfus PM, Victor M (1961) Effects of thiamine deficiency on the central nervous system. American Journal of Clinical Nutrition 9: 414-425.

Evans CA, Carlson WE, Green EG (1942) The pathology of Chastek paralysis in foxes. A counterpart of Wernicke's hemorrhagic polioencephalitis of man. American Journal of Pathology 18:79-90.

Freo U (1996) Cerebral metabolic effects of serotonin drugs and neurotoxins. Life Sci 1996;59(11):877-91

Gilles FH (1963) Selective symmetrical neuronal necrosis of certain brain stem tegmental nuclei in temporary cardiac standstill. Journal of Neuropathology and Experimental Neurology 22:318-318.

Gilles FH (1969) Hypotensive brain stem necrosis: selective symmetrical necrosis of tegmental neuronal aggregates following cardiac arrest. Archives of Pathology 88:32-41.

Goulon M, Nouailhat R, Escourolle R, Zarranz-Imirizaldu JJ, Grosbuis S, Levy-Alcover MA (1975). Intoxication par le bromure de methyl: Trois observations, dont une mortelle. Etude neuro-pathologique d'un cas de stupeur avec myoclonies, suivi pendent cinq ans. Revue Neurologique (Paris) 131:445-468.

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Griffiths AD, Laurence KM (1974) The effect of hypoxia and hypoglycemia on the brain of the newborn human infant. Developmental Medicine and Child Neurology 16:308-319.

Grunnet ML, Curless RG, Bray PF, Jung AL (1974) Brain changes in newborns from an intensive care unit. Developmental Medicine and Child Neurology 16:320-328.

Hakim AM (1986) Effect of thiamine deficiency and its reversal on cerebral blood flow in the rat. Observations on the phenomena of hyperperfusion, "no reflow," and delayed hypoperfusion. Journal of Cerebral Blood Flow and Metabolism 6:79-85

Hakim AM and Pappius HM (1981) The effect of thiamine deficiency on local cerebral glucose utilization. Annals of Neurology 9:334-339.

Irle E, Markowitsch HJ (1983) Widespread neuroanatomical damage and learning deficits following chronic alcohol consumption or vitamin B1 (thiamine) deficiency in rats. Behavioral Brain Research 9:277-284.

Jacobson HN & Windle WF (1960) Responses of foetal and new-born monkeys to asphyxia. The Journal of Physiology (London) 153:447-456.

Johnston MV, Goldstein GW (1998) Selective vulnerability of the developing brain to lead. Current Opinion in Neurology 11:689-693

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Kelly PA, Ritchie IM, McBean DE, Sharkey J, Olverman HJ (1995) Enhanced cerebrovascular responsiveness to hypercapnia following depletion of central serotonergic terminals. Journal of Cerebral Blood Flow and Metabolism 15:706-713

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Leech RW, Alvord EC (1977) Anoxic-ischemic encephalopathy in the human neonatal period, the significance of brain stem involvement. Archives of Neurology 34:109-113.

Lucey JF, Hibbard E, Behrman RE, Esquival FO, Windle WF (1964) Kernicterus in asphyxiated newborn monkeys. Experimental Neurology 9:43-58.

Malamud N, Skillicorn SA (1956). Relationship between the Wernicke and the Korsakoff Syndrome. Archives of Neurology and Psychiatry, 76, 585-596.

Mirsky AF, Orren MM, Stanton L, Fullerton BC, Harris S, Myers RE (1979) Auditory evoked potentials and auditory behavior following prenatal and perinatal asphyxia in rhesus monkeys. Developmental Psychobiology 12:369-379

Myers R (1972) Two patterns of perinatal brain damage and their conditions of occurrence. American Journal of Obstetrics and Gynecology 112:246-276.

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Oyanagi K, Ohama E, and Ikuta F (1989). The auditory system in methyl mercurial intoxication: a neuropathological investigation on 14 autopsy cases in Niigata, Japan. Acta Neuropathologica (Berlin), 77, 561-568.

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Ranck JB, Windle WF (1959). Brain damage in the monkey, Macaca mulatta, by asphyxia neonatorum. Experimental Neurology 1:130-154.

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Squier MV, Thompson J, Rajgopalan B. (1992) Case report: neuropathology of methyl bromide intoxication. Neuropathology and Applied Neurobiology 18: 579-584.

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