Mapping of Functional Neural Pathways by Autoradiographic Survey of Local Metabolic Rate with [
            <sup>14</sup>
            C]Deoxyglucose

Kennedy, Charles; Rosiers, MH Des; Jehle, Jane; Reivich, Martin; Sharpe, F. T.; Sokoloff, Louis

doi:10.1126/science.1114332

Cited by 431 publications

(104 citation statements)

References 7 publications

(2 reference statements)

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“…See Table 5a for a description. greatest metabolic demands are thought to occur at post-synaptic sites during generation of exhitatory and inhibitory post-synaptic potentials (EPSP's and IPSP's) (Sokoloff 1977;Kennedy et al 1975;Jueptner and Weiller 1995). As mentioned, alpha-2 receptors can be pre-or post-synaptic, but the evidence suggests their actions in PFC be mediated through post-synaptic receptors.…”

Section: Discussionmentioning

confidence: 99%

The Effects of an Alpha-2 Adrenergic Agonist, Guanfacine, on rCBF in Human Cortex in Normal Controls and Subjects with Focal Epilepsy

Swartz

Kovalik²,

Thomas³

et al. 2000

Neuropsychopharmacology

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Alpha-2 noradrenergic agonists may have wide applicability in the treatment of pre-frontal cortex deficits in primates and behavioral dysfunction in man. We have undertaken this study to determine the effect of an alpha-2 agonist, guanfacine, on regional cerebral blood flow (rCBF) in humans. Three subject groups were evaluated: normal controls, subjects with frontal lobe epilepsy (FLE), and subjects with temporal lobe epilepsy (TLE). All underwent a number of PET scans using 15 O-water, with A growing body of evidence has established that norepinephrine (NE) plays an important role in the performance of cognitive functions in a variety of species (Stein et al. 1975;Oke and Adams 1978;McEntee and Mair 1980;Carli et al. 1983;McGaugh et al. 1984;Leslie et al. 1985). Aged monkeys and young monkeys with either surgical ablations or toxin-induced catecholamine depletion in the prefrontal region (principal sulcus) are unable to perform delayed-response tasks (Bartus et al. 1978;Goldman and Rosvold 1979;Brozoski et al. 1979). Arnsten and colleagues studied rhesus monkeys from 17 to over 30 years in age, and found improved baseline performance on a spatial delayed non-match to sample task following a single dose of the alpha-2 agonist, clonidine (Arnsten and Goldman-Rakic 1985). There were both dose and interval NO . 3 (delay) interactions, with greater effects observed as the delay was lengthened. Yohimbine, an alpha-2-antagonist, blocked the effect while neither beta nor alpha-1 antagonists did. A later study showed that guanfacine, an alpha-2A agonist, was 10-1000 times more potent than clonidine in this effect (Arnsten et al. 1988).The alpha-2A adrenergic receptor subtype appears to be the site of action of the beneficial effects of alpha-2 agonists on prefrontal cortex (PFC) function (reviewed in Arnsten et al. 1996;Arnsten 1998). Alpha-2A receptors are localized both pre-and post-synaptically, but several lines of evidence suggest that the site of action is post-synaptic in PFC (Arnsten and Goldman-Rakic 1985;Cai et al. 1993). Their effects on working memory are more pronounced in animals with cell loss or catecholamine depletion, being found at low concentrations in old or depleted monkeys but only at high concentrations in young intact monkeys (Franowicz and Arnsten 1998;Arnsten and Goldman-Rakic 1985 1990;Cai et al. 1993). Stimulation of the locus coeruleus produces a largely inhibitory effect on cortical neurons, whereas a presynaptic action would be expected to produce disinhibition through reduced NE release (Langer 1974). Iontophoresis of the alpha-2 antagonist, yohimbine in monkey PFC neurons suppresses delay-related cellular activity during working memory tasks (Li and Kubota 1998; Sawaguchi 1998). Systemic clonidine enhances this delay-related activity, and this enhancement is reversed by iontophoresis of yohimbine in PFC.Efficacy has also been found with clonidine in an object working memory paradigm, a function believed to rely on ventral prefrontal regions (Jackson and Buccafusco 1991). High ...

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Section: Discussionmentioning

confidence: 99%

The Effects of an Alpha-2 Adrenergic Agonist, Guanfacine, on rCBF in Human Cortex in Normal Controls and Subjects with Focal Epilepsy

Swartz

Kovalik²,

Thomas³

et al. 2000

Neuropsychopharmacology

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“…This belief is based on 2-deoxyglucose experiments conducted on monkeys (Kennedy, Des Rosiers, Jehle, Reivich, Sharpe & Sokoloff, 1975;Kennedy, des Rosiers, Sakurada, Shinohara, Reivich, Jehle & Sokoloff, 1976;Horton, 1984;LeVay, Connolly, Houde & Van Essen, 1985). The blind spot is represented as a disk in the striate cortex, driven entirely by the ipsilateral eye and devoid of ocular dominance columns.…”

Section: Blind Spot Contour Interaction Long-range Horizontal Connectmentioning

confidence: 99%

Long-range dichoptic interactions in the human visual cortex in the region corresponding to the blind spot

Tripathy

Levi

1994

Vision Research

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Tbe region of tbe visual field of one eye tbat corresponds to tbe blind spot of the coutraIatera1 eye is beiieved to be monocular. We measured dicboptic coatour interaction in this region of tbe visual field in bumans by having observers report tbe orientation of a test letter "T" presenH to tbis region, in the presence of thud&g T's presented around tbe blind spot of the fellow eye. A large drop in performance was seen because of tbe Bauks, showing clearly tbe existence of dicboptic contour interaction in this 'cmonocular" region of tbe visual field. Tbis suggests that the cortical representatioa of the region of tbe visual field tbat corresponds to the -t&ate& eye's blind spot is sot strictly monocular. Tbe absence of direct retinal aiferents from oue eye to tbis region of cortex swggests tbe involvement of horizontal cortical connectious in tbe contour interaction phenomenon. Our estimates of the extent of contour interaction in mm of striate cortex are comparable to the reported lengths of the long-range horizontal connections in tbe striate cortex of monkeys. Our results are consistent with the proposition that long-range horizontal conuections of the striate cortex may mediate the eontour interaction p~~rnenon.

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“…Regional brain activity was determined by measuring [ 14 C]-2DG uptake (Kennedy et al, 1975) as previously described elsewhere (Kennedy et al, 1975;Duncan et al, 1999) with minimal modifications. Animals were injected with ketamine (30 mg/kg, i.p.)…”

Section: Methodsmentioning

confidence: 99%

GluN2D N-Methyl-D-Aspartate Receptor Subunit Contribution to the Stimulation of Brain Activity and Gamma Oscillations by Ketamine: Implications for Schizophrenia

Sapkota

Mao

Synowicki

et al. 2015

Journal of Pharmacology and Experimental Therapeutics

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The dissociative anesthetic ketamine elicits symptoms of schizophrenia at subanesthetic doses by blocking N-methyl-Daspartate receptors (NMDARs). This property led to a variety of studies resulting in the now well-supported theory that hypofunction of NMDARs is responsible for many of the symptoms of schizophrenia. However, the roles played by specific NMDAR subunits in different symptom components are unknown. To evaluate the potential contribution of GluN2D NMDAR subunits to antagonist-induced cortical activation and schizophrenia symptoms, we determined the ability of ketamine to alter regional brain activity and gamma frequency band neuronal oscillations in wild-type (WT) and GluN2D-knockout (GluN2D-KO) mice. In WT mice, ketamine (30 mg/kg, i.p.) significantly increased [14 C]-2-deoxyglucose ([ 14 C]-2DG) uptake in the medial prefrontal cortex (mPFC), entorhinal cortex and other brain regions, and decreased activity in the somatosensory cortex and inferior colliculus. In GluN2D-KO mice, however, ketamine did not significantly increase [14 C]-2DG uptake in any brain region examined, yet still decreased [14 C]-2DG uptake in the somatosensory cortex and inferior colliculus. Ketamine also increased locomotor activity in WT mice but not in GluN2D-KO mice. In electrocorticographic analysis, ketamine induced a 111% 6 16% increase in cortical gamma-band oscillatory power in WT mice, but only a 15% 6 12% increase in GluN2D-KO mice. Consistent with GluN2D involvement in schizophrenia-related neurologic changes, GluN2D-KO mice displayed impaired spatial memory acquisition and reduced parvalbumin (PV)-immunopositive staining compared with control mice. These results suggest a critical role of GluN2D-containing NMDARs in neuronal oscillations and ketamine's psychotomimetic, dissociative effects and hence suggests a critical role for GluN2D subunits in cognition and perception.

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Mapping of Functional Neural Pathways by Autoradiographic Survey of Local Metabolic Rate with [ ¹⁴ C]Deoxyglucose

Cited by 431 publications

References 7 publications

The Effects of an Alpha-2 Adrenergic Agonist, Guanfacine, on rCBF in Human Cortex in Normal Controls and Subjects with Focal Epilepsy

The Effects of an Alpha-2 Adrenergic Agonist, Guanfacine, on rCBF in Human Cortex in Normal Controls and Subjects with Focal Epilepsy

Long-range dichoptic interactions in the human visual cortex in the region corresponding to the blind spot

GluN2D N-Methyl-D-Aspartate Receptor Subunit Contribution to the Stimulation of Brain Activity and Gamma Oscillations by Ketamine: Implications for Schizophrenia

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Mapping of Functional Neural Pathways by Autoradiographic Survey of Local Metabolic Rate with [ 14 C]Deoxyglucose

Cited by 431 publications

References 7 publications

The Effects of an Alpha-2 Adrenergic Agonist, Guanfacine, on rCBF in Human Cortex in Normal Controls and Subjects with Focal Epilepsy

The Effects of an Alpha-2 Adrenergic Agonist, Guanfacine, on rCBF in Human Cortex in Normal Controls and Subjects with Focal Epilepsy

Long-range dichoptic interactions in the human visual cortex in the region corresponding to the blind spot

GluN2D N-Methyl-D-Aspartate Receptor Subunit Contribution to the Stimulation of Brain Activity and Gamma Oscillations by Ketamine: Implications for Schizophrenia

Contact Info

Product

Resources

About

Mapping of Functional Neural Pathways by Autoradiographic Survey of Local Metabolic Rate with [ ¹⁴ C]Deoxyglucose