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Edward G Jones

Publications and source records attributed to Edward G Jones.

10 recordsLinked to original sources
PubMed2004

Gender-specific gene expression in post-mortem human brain: localization to sex chromosomes.

Gender differences in brain development and in the prevalence of neuropsychiatric disorders such as depression have been reported. Gender differences in human brain might be related to patterns of gene expression. Microarray technology is one useful method for investigation of gene expression in brain. We investigated gene expression, cell types, and regional expression patterns of differentially expressed sex chromosome genes in brain. We profiled gene expression in male and female dorsolateral prefrontal cortex, anterior cingulate cortex, and cerebellum using the Affymetrix oligonucleotide microarray platform. Differentially expressed genes between males and females on the Y chromosome (DBY, SMCY, UTY, RPS4Y, and USP9Y) and X chromosome (XIST) were confirmed using real-time PCR measurements. In situ hybridization confirmed the differential expression of gender-specific genes and neuronal expression of XIST, RPS4Y, SMCY, and UTY in three brain regions examined. The XIST gene, which silences gene expression on regions of the X chromosome, is expressed in a subset of neurons. Since a subset of neurons express gender-specific genes, neural subpopulations may exhibit a subtle sexual dimorphism at the level of differences in gene regulation and function. The distinctive pattern of neuronal expression of XIST, RPS4Y, SMCY, and UTY and other sex chromosome genes in neuronal subpopulations may possibly contribute to gender differences in prevalence noted for some neuropsychiatric disorders. Studies of the protein expression of these sex-chromosome-linked genes in brain tissue are required to address the functional consequences of the observed gene expression differences.

Actins↗
PubMed2003

Fine structural localization of connexin-36 immunoreactivity in mouse cerebral cortex and thalamus.

The mounting physiological evidence for low-resistance electrical coupling between thalamic and cortical neurons contrasts with a lack of morphological data on gap junctions in thalamus and cortex. Connexin-36 is a neuronally specific protein associated with low-resistance gap junctions in the central nervous system. Connexin-36 localization was studied in the mouse somatosensory cortex and thalamus by using immunocytochemistry and immunoelectron microscopy. Expression of connexin-36 immunoreactivity is widespread in the forebrain and significantly enhanced in the barrel cortex and thalamic reticular nucleus during the second postnatal week, but it extends to other thalamic nuclei as well. At the electron microscopic level, pre- and postembedding immunogold labeling revealed that 70-76% of connexin-36-immunolabeled particles were localized at focal sites on apposed plasma membranes of cortical and thalamic dendrites; approximately 5% of the particles were associated with parasynaptic membranes; but on no occasion could overt, morphologically identifiable gap junctions be demonstrated in association with connexin-36 immunoreactivity. The widespread distribution of focal concentrations of connexin-36 subunits could provide a basis for the electrical coupling that exists between cortical and reticular thalamic neurons, but morphologically definable gap junctions may be too small to be adequately visualized by conventional immunoelectron microscopy.

Animals↗
PubMed2003

Corticothalamic inhibition in the thalamic reticular nucleus.

Mutual inhibition between the GABAergic cells of the thalamic reticular nucleus (RTN) is important in regulating oscillations in the thalamocortical network, promoting those in the spindle range of frequencies over those at lower frequencies. Excitatory inputs to the RTN from the cerebral cortex are numerically large and particularly powerful in inducing spindles. However, the extent to which corticothalamic influences can engage the inhibitory network of the RTN has not been fully explored. Focal electrical stimulation of layer VI in the barrel cortex of the mouse thalamocortical slice in vitro resulted in prominent di- or polysynaptic inhibitory postsynaptic currents (IPSCs) in RTN cells under the experimental conditions used. The majority of cortically induced responses consisted of mixed PSCs in which the inhibitory component predominated or of large IPSCs alone, implying inhibition of neighboring cells by other, cortically excited RTN cells. Within the mixed PSCs, fixed and variable latency components could commonly be identified. IPSCs could be blocked by application of ionotropic glutamate receptor antagonists or of GABA(A) receptor antagonists, also indicating their dependence on corticothalamic excitation triggering disynaptic or polysynaptic inhibition. Spontaneous GABA(A) receptor-dependent IPSCs were routinely observed in the RTN and, taken together with the results of cortical stimulation, indicate the existence of a substantial network of intrareticular inhibitory connections that can be effectively recruited by the corticothalamic system. These results suggest activation of cortical excitatory inputs triggers the propagation of inhibitory currents within the RTN and support the view that activation of the RTN from the somatosensory cortex, although focused by the topography of the corticothalamic projection, is capable of disynaptically engaging the whole inhibitory network of the RTN, by local and probably by reentrant GABA(A) receptor-based synapses, thus spreading the corticothalamic influence throughout the RTN.

6-Cyano-7-nitroquinoxaline-2,3-dione↗
PubMed2003

Two epochs in the development of gamma-aminobutyric acidergic neurons in the ferret thalamus.

These studies chart the development of gamma-aminobutyric acid (GABA)-ergic neurons in the three divisions of the thalamus (ventral thalamus, dorsal thalamus, and epithalamus). GABAergic neurons were identified by in situ hybridization to localize mRNA for 67-kDa glutamic acid decarboxylase (GAD(67)) and related to the morphological maturation of the thalamus in fetal and postnatal brains and to expression of transcription factors Gbx-2 and Tbr-1. Origins of GABAergic neurons were sought in in vitro slice preparations incubated in bromodeoxyuridine or injected with a carbocyanine dye. GABA neurons of ventral thalamus (reticular nucleus, ventral lateral geniculate nucleus, zona incerta, and nucleus of the fields of Forel) and of epithalamus appear at least 14 days before those intrinsic to dorsal thalamus. Ventral thalamus GABA cells are derived from a region connecting the ventricular zone of the third ventricle to the caudal ganglionic eminence. This region is delimited ventrally by the Tbr-1-expressing prethalamic eminence and dorsally by the Gbx-2-expressing part of the dorsal thalamus. GABA neurons of epithalamus are derived from the embryonic pretectum. Neurons continue to be added to the ventral thalamus, perireticular nucleus, entopeduncular nucleus, and substantia nigra from the ganglionic eminence as development proceeds. GAD(67)-expressing cells of dorsal thalamus become detectable only at birth and populate the thalamus from posterior to anterior over the first week of life. Although a very small number reaches the dorsal lateral geniculate nucleus from the caudal ganglionic eminence, there is no obvious new source of proliferating neurons at this stage. Intrinsic GABA cells of dorsal thalamus may, therefore, derive from an early generated population of cells that turns on a GABAergic phenotype only late in development.

Animals↗
PubMed2003

MRNA expression patterns and distribution of white matter neurons in dorsolateral prefrontal cortex of depressed patients differ from those in schizophrenia patients.

BACKGROUND: Schizophrenia, bipolar illness, and major depressive disorder have distinct presentations, but share some common symptoms. Hence, some common cellular and molecular abnormalities may be identifiable in these disorders. METHODS: We examined cell-specific markers in the dorsolateral prefrontal cortex of brains from 18 patients with bipolar or major depressive disorder, and 18 matched controls, using in situ hybridization histochemistry and staining for nicotinamide-dinucleotide phosphate-diaphorase (NADPH). The distribution of NADPH-positive interstitial cells of the white matter and the expression of the mRNA for the 67 KD form of glutamic acid decarboxylase (GAD(67)) had previously been shown to be altered in prefrontal cortex of schizophrenics. Other markers identifying glutamatergic neuronal populations were alpha-type II calcium/calmodulin dependent protein kinase (CAMKII-alpha), brain derived neurotrophic factor, (BDNF) and the putative transcription factor, T-brain-1 (TBR1). RESULTS: Expression of GAD67 and the distribution of NADPH-positive cells in the white matter were not significantly altered in the dorsolateral prefrontal cortex of depressed subjects. Expression of CAMKII-alpha and TBR1 mRNAs was significantly increased in bipolar patients but not in major depressed patients, and there was a trend toward reduced BDNF expression in both groups. Abnormal patterns of gene expression and neuronal distribution in schizophrenics are markedly different from those in depressed patients. CONCLUSIONS: The findings that TBR1 and CAMKII-alpha expression is increased only in bipolar patients suggests abnormalities of specific genes related to a major cortical cell type and its connectivity.

Adult↗
PubMed2003

Microarray technology: a review of new strategies to discover candidate vulnerability genes in psychiatric disorders.

OBJECTIVE: An international effort is in progress to discover candidate genes and pathways associated with psychiatric disorders, including two of the most serious diseases, schizophrenia and mood disorders, through the use of new technology-microarrays. Instead of studying one gene at a time, microarrays provide the opportunity to analyze thousands of genes at once. METHOD: This article reviews the steps in this discovery process, including the acquisition and characterization of high-quality postmortem brain tissue, RNA extraction, and preparation and use of microarray technology. Two alternative microarray methods and factors affecting the quality of array data are reviewed. RESULTS: New analytical strategies are being developed to process the massive data sets generated by microarray studies and to define the significance of implicated genes. Array results must be validated by other methods, including in situ hybridization and real-time polymerase chain reaction. Identified genes can also be evaluated in terms of their chromosomal locations and possible overlap with regions of suggestive linkage or association identified with genome-wide linkage analysis in psychiatry and in terms of overlap with genes identified by microarray studies in animals administered psychoactive drugs. Microarray studies are only the first major step in the process. Further efforts in the investigation involve multiple strategies for studying function and gene structure, including transgenic and knockout animal studies. CONCLUSIONS: Microarrays present a methodology that can identify genes or pathways for new and unique potential drug targets, determine premorbid diagnosis, predict drug responsiveness for individual patients, and, eventually, initiate gene therapy and prevention strategies.

Brain Chemistry↗
PubMed2002

Thalamic circuitry and thalamocortical synchrony.

The corticothalamic system has an important role in synchronizing the activities of thalamic and cortical neurons. Numerically, its synapses dominate the inputs to relay cells and to the gamma-amino butyric acid (GABA)ergic cells of the reticular nucleus (RTN). The capacity of relay neurons to operate in different voltage-dependent functional modes determines that the inputs from the cortex have the capacity directly to excite the relay cells, or indirectly to inhibit them via the RTN, serving to synchronize high- or low-frequency oscillatory activity respectively in the thalamocorticothalamic network. Differences in the alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) subunit composition of receptors at synapses formed by branches of the same corticothalamic axon in the RTN and dorsal thalamus are an important element in the capacity of the cortex to synchronize low-frequency oscillations in the network. Interactions of focused corticothalamic axons arising from layer VI cortical cells and diffuse corticothalamic axons arising from layer V cortical cells, with the specifically projecting core relay cells and diffusely projecting matrix cells of the dorsal thalamus, form a substrate for synchronization of widespread populations of cortical and thalamic cells during high-frequency oscillations that underlie discrete conscious events.

Animals↗
PubMed2002

Temporal and regional expression of NMDA receptor subunit NR3A in the mammalian brain.

NR3A is a developmentally regulated N-methyl-D-aspartate receptor (NMDAR) subunit that was previously known as NMDAR-L or chi-1. Unlike other NMDAR subunits, NR3A inhibits the NMDAR-associated ion channel in a novel manner, and a role in synaptogenesis has been suggested for this subunit. Here, we report a comprehensive study to delineate the temporal and anatomic expression of NR3A protein in the mammalian brain by using a monoclonal anti-NR3A antibody. NR3A protein was found to peak at postnatal day (P) 8, and to decrease gradually from P12 to adulthood in the rat central nervous system. Moreover, NR3A protein was heavily expressed in all areas of the isocortex, portions of the amygdaloid nuclei, and selective cell layers and nuclei of the hippocampus, thalamus, hypothalamus, brainstem, and spinal cord. NR3A protein was also expressed in the cerebellar cortex, whereas only weak signal was detected in the previous in situ studies by using riboprobes. At an ultrastructural level, NR3A was associated specifically with asymmetrical synapses and localized to postsynaptic membranes. This information will facilitate future research on NMDARs by providing clues to possible inclusion of the NR3A subunit in NMDARs in many brain regions.

Animals↗
PubMed2002

Thalamic organization and function after Cajal.

Cajal's many contributions to understanding the thalamus have been hidden by his body of work on the cerebral cortex. He delineated many thalamic nuclei in rodents, defined afferent fibers, thalamocortical relay neurons and interneurons, was first to demonstrate thalamocortical fibers and their terminations in the cortex, and recognized the feed-back provided by corticothalamic fibers. This presentation outlines modern methods for identifying classes of thalamic neurons, their chemical characteristics, synaptology and differential connections, and describes the intrinsic circuitry of the thalamus, showing how interactions between GABAergic cells of the reticular nucleus and glutamatergic relay cells underlie rhythmic activities of neurons in the thalamo-cortico-thalamic network, activities associated with changes in the conscious state, and which are generated and maintained by the corticothalamic projection. Corticothalamic fibers interact with reticular nucleus cells and relay cells through NMDA, AMPA and metabotropic receptors while interactions between reticular nucleus cells and relay cells are mediated by GABAA and GABAB receptors. Differing strengths of synaptic input to the two cell types, from which oscillatory behavior commences, depend upon differential expression at individual synapses of specific AMPA receptor subunits which modulate excitatory postsynaptic conductances. Two classes of relay cells can be distinguished by differential staining for calbindin and parvalbumin. The first forms a matrix in the thalamus, unconstrained by nuclear borders; the second is concentrated in certain nuclei in which it forms the topographically organized core. In projecting diffusely to the cortex, calbindin cells provide a substrate for binding together activities of multiple cortical areas that receive focused input from single thalamic nuclei. This, and the presence of specific and diffuse corticothalamic projections may serve to promote coherent activity of large populations of cortical and thalamic neurons in perception, attention and conscious awareness.

Animals↗