Scott Manaker

Identification of Sodium-Dependent, High-Affinity Choline Uptake Sites in Rat Brain with [3H]Hemicholinium-3

Abstract: [3H]Hemicholinium‐3 (HC‐3) was used to label sodium‐dependent, high‐affinity choline uptake sites in regions of rat brain. Autoradiography revealed a high density of [3H]HC‐3 binding sites in brain regions with a high density of cholinergic terminals, such as the interpeduncular nucleus, caudate‐putamen, and olfactory tubercle. This distribution of [3H]HC‐3 binding sites was in close agreement with the amounts of choline acetyltrans‐ferase in specific nuclei and subregions of rat brain. Destruction of presynaptic cholinergic projections in the cerebral cortex and the basal ganglia by injection of excitotoxins reduced [3H]HC‐3 binding by 40–50%. These data indicate that sodium‐dependent [3H]HC‐3 binding sites are related to the choline transport system present in cholinergic neurons.

Localization and quantification of beta‐adrenergic receptors in human brain

Little information is currently available on the localization of noradrenergic systems in the human CNS. We used quantitative autoradiography with [125I] iodopindolol to examine beta-adrenergic receptors in postmortem human brain. The concentration of beta-receptors was highest in all subfields of the hippocampus, followed by cerebellum, and then thalamic nuclei, basal ganglia, midbrain, and cerebral cortex. Low levels were found in white matter and hypothalamus. This distribution differed from the distribution of beta-receptors reported in membrane homogenates of human brain and also from the distribution of beta-receptors in rat brain determined by autoradiography. The similarities and differences between the distribution of beta-receptors in the human and rat brains may have implications regarding the role of norepinephrine in the CNS of these two species.

Localization in rat brain of binding sites for parkinsonian toxin MPTP: similarities with [3H]parygyline binding to monoamine oxidase

A high-affinity binding site exists in rat brain for the parkinsonian toxin 1-methyl-4-phenyl-1,2,5,6-tetrahydropyridine (MPTP). The pharmacological specificity of this binding site suggests that it may correspond to monoamine oxidase (MAO). We have used quantitative autoradiography to map in detail the anatomical distribution of the [3H]MPTP binding site in rat brain and compared it with the anatomical distribution of MAO as determined by in vitro autoradiography with [3H]pargyline. Under the conditions of the assay, [3H]pargyline labeled the type B form of MAO. There were strong similarities in the anatomical distribution of [3H]MPTP and [3H]pargyline, with high levels of both binding sites occurring in the arcuate nucleus, the locus coeruleus, the dorsal raphe nucleus and all circumventricular organs. Low levels of both binding sites were found in the substantia nigra and the caudate-putamen. These results provide additional evidence that the high-affinity binding site for MPTP is MAO. The parkinsonian actions of MPTP might result from metabolites produced by MAO.

Autoradiographic localization of thyrotropin‐releasing hormone (TRH) receptors in human spinal cord

Thyrotropin-releasing hormone (TRH) exerts many effects upon spinal cord function in animals, and may also play a role in human spinal cord function. We have used the technique of quantitative autoradiography to anatomically localize specific receptors for TRH within human spinal cord. Highest concentrations of TRH receptors were localized within lamina II, the substantia gelatinosa. A moderate density of TRH receptors was found in lamina IX, the motor neurons of the anterior horn. Low levels of TRH receptors were noted throughout the remainder of the gray matter of the human spinal cord, and no TRH receptors were localized within white matter. This anatomic distribution of TRH receptors within the human spinal cord is consistent with the localization of endogenous TRH and the effects of exogenously applied TRH in animal studies. These results suggest that any effects of TRH on human spinal cord function may be mediated by TRH receptors.

Autoradiographic localization of thyr tropin releasing hormone receptors in human brain

We used quantitative autoradiography to localize thyrotropin releasing hormone (TRH) receptors in human brain. Highest concentrations of TRH receptors were localized within the cortical, basal, and lateral nuclei of the amygdala and the molecular layer of the hippocampus. Low levels were found in the cortex, diencephalon, and basal ganglia. The radioligand bound with similar affinity and pharmacology to pituitary gland as to brain. These data suggest that authentic TRH receptors in the hippocampus and amygdala may mediate the putative effects of TRH on the human brain.

Colocalization of substance P or enkephalin in serotonergic neuronal afferents to the hypoglossal nucleus in the rat

The serotonergic innervation of the hypoglossal nucleus originates from the caudal raphe nuclei. Non‐serotonergic neurons in the caudal raphe nuclei also project to the hypoglossal nucleus. We employed a triple‐fluorescence technique to determine whether the substance P‐ or the enkephalin‐containing neurons in the caudal raphe nuclei that projected to the hypoglossal nucleus also contained serotonin. Rhodamine latex microspheres were injected into the hypoglossal nucleus, and then serotonin and peptide dual‐immunofluorescence was performed to colocalize perikarya containing serotonin, substance P, and rhodamine microspheres; or perikarya containing serotonin, enkephalin, and rhodamine microspheres. Our results demonstrate that most substance P‐containing neuronal afferents to the hypoglossal nucleus colocalize serotonin. In contrast, few enkephalin‐containing neuronal afferents to the hypoglossal nucleus also contain serotonin. These data suggest that substance P projections to the hypoglossal nucleus are a subset of serotonergic projections and that limited overlap exists between the populations of enkephalinergic and serotonergic neuronal afferents to the hypoglossal nucleus. Either substance P‐ or enkephalin‐containing somata account for a very small proportion of non‐serotonergic caudal raphe projections to the hypoglossal nucleus. Finally, these data demonstrate the medial tegmental field origins of the substance P projections and the enkephalin projections to the hypoglossal nucleus. J. Comp. Neurol. 391:491–505, 1998.

Ten Commandments for Effective Clinical Decision Support for Imaging: Enabling Evidence-Based Practice to Improve Quality and Reduce Waste

OBJECTIVE We describe best practices for effective imaging clinical decision support (CDS) derived from firsthand experience, extending the Ten Commandments for CDS published a decade ago. Our collective perspective is used to set expectations for providers, health systems, policy makers, payers, and health information technology developers. CONCLUSION Highlighting unique attributes of effective imaging CDS will help radiologists to successfully lead and optimize the value of the substantial federal and local investments in health information technology in the United States.

Neurons of the motor trigeminal nucleus project to the hypoglossal nucleus in the rat.

SummaryThe hypoglossal nucleus (Mo12) contains motoneurons that innervate the tongue, while the motor trigeminal nucleus (Mo5) contains motoneurons that elevate or depress the mandible. Previous studies have revealed lateral and medial tegmental field neuronal afferents to the Mo12 adjacent to, but not within, the motor trigeminal nucleus (Mo5). The current studies demonstrate the presence of retrogradely labeled neuronal afférents to the Mo12 within the Mo5 produced by as little as 10 nl of Fast Blue (FB) injected into the Mo12. Retrograde labeling of Mo5 afferents to the Mo12 with injections of Diamidino Yellow (DY) combined with injections of FB into the lumbar spinal cord showed these neuronal afferents to the Mo12 are not part of the diffuse projections to motoneurons from the nucleus subcoeruleus. Retrograde labeling of Mo5 afferents to the Mo12 with DY combined with injections of FB into the masseter revealed these neuronal afferents to the Mo12 are not trigeminal motoneurons. These results indicate that Mo5 interneurons are part of the lateral tegmental field projections to the Mo12, and are likely to comprise part of the neural substrate coordinating the motor activity of the jaw and tongue.

Autoradiographic localization of neurotransmitter binding sites in the hypoglossal and motor trigeminal nuclei of the rat.

The hypoglossal and motor trigeminal nuclei contain somatic motoneurons innervating the tongue, jaw, and palate. These two cranial motor nuclei are myotopically organized and contain neurotransmitter binding sites for thyrotropin‐releasing hormone, substance P, and serotonin. Quantitative autoradiography was used to localize thyrotropin‐releasing hormone, substance P, and serotonin‐1A and serotonin‐1B binding sites in the hypoglossal and motor trigeminal nuclei and to relate the relative distributions of these binding sites to the myotopic organizations of the two nuclei. In the hypoglossal nucleus, high‐to‐moderate concentrations of all four binding sites were present in the dorsal and ventromedial subnuclei, whereas low concentrations were noted in the ventrolateral subnucleus. In the motor trigeminal nucleus, high concentrations of serotonin‐1B, moderate densities of thyrotropin‐releasing hormone, and low levels of substance P and serotonin‐1A binding sites were present in both the ventromedial and dorsolateral subnuclei. These observations demonstrate that neurotransmitter binding sites in the hypoglossal and motor trigeminal nuclei are heterogeneously localized and that their distributions correspond to the previously described myotopic organizations of each nucleus. Synapse 28:44–59, 1998.

TRH and TRH Receptors in the Spinal Cord

Over the past 12 years, substantial progress has been made in delineating the localization of TRH and TRH receptors in spinal cord. High concentrations of both the peptide and its receptor have been observed in the ventral horn in the region of the motoneurons and in the dorsal horn in the substantia gelatinosa. As noted, pharmacological effects of TRH administration on various parameters of spinal cord function have been reported in a number of studies. To date, however, substantial questions remain regarding the physiological role of TRH in the spinal cord. Nevertheless, it is hoped that the extensive information that has been obtained on localization of TRH and TRH receptors in spinal cord will provide a basis for answering these complex questions.