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T Curran

Publications and source records attributed to T Curran.

At least 37 records · Page 2Linked to original sources
PubMed2000

Brain potentials of recollection and familiarity.

It is widely hypothesized that separate recollection and familiarity processes contribute to recognition memory. The present research measured event-related brain potentials (ERPs) from 128 head locations to identify patterns of brain activity related to recollection and familiarity. In two experiments, subjects performed a recognition memory task requiring discrimination between previously studied words, similar words that changed plurality between study and test, and new words (following Hintzman & Curran, 1994). The FN400 ERP component (300-500 msec) varied with the familiarity of words (new > studied = similar). The parietal component (400-800 msec) was associated with the recollection of plurality (studied > similar = new). Differences in the timing and spatial topography of the FN400 and parietal effects support the view that familiarity and recollection arise from distinct neurocognitive processes.

Adult↗
PubMed1999

Disabled-1 binds to the cytoplasmic domain of amyloid precursor-like protein 1.

Disruption of the disabled-1 gene (Dab1) results in aberrant migration of neurons during development and disorganization of laminar structures throughout the brain. Dab1 is thought to function as an adapter molecule in signal transduction processes. It contains a protein-interaction (PI) domain similar to the phosphotyrosine-binding domain of the Shc oncoprotein, it is phosphorylated by the Src protein tyrosine kinase, and it binds to SH2 domains in a phosphotyrosine-dependent manner. To investigate the function of Dab1, we searched for binding proteins using the yeast two-hybrid system. We found that the PI domain of Dab1 interacts with the amyloid precursor-like protein 1 (APLP1). The association of Dab1 with APLP1 was confirmed in biochemical assays, and the site of interaction was localized to a cytoplasmic region of APLP1 containing the amino acid sequence motif Asn-Pro-x-Tyr (NPxY). NPxY motifs are involved in clathrin-mediated endocytosis, and they have been shown to bind to PI domains present in several proteins. This region of APLP1 is conserved among all members of the amyloid precursor family of proteins. Indeed, we found that Dab1 also interacts with amyloid precursor protein (APP) and APLP2 in biochemical association experiments. In transiently transfected cells, Dab1 and APLP1 colocalized in membrane ruffles and vesicular structures. Cotransfection assays in cultured cells indicated that APP family members increased serine phosphorylation of Dab1. Dab1 and APLP1 are expressed in similar cell populations in developing and adult brain tissue. These results suggest that Dab1 may function, at least in part, through association with APLP1 in the brain.

Adaptor Proteins, Signal Transducing↗
PubMed1999

Thyroid hormone regulates reelin and dab1 expression during brain development.

The reelin and dab1 genes are necessary for appropriate neuronal migration and lamination during brain development. Since these processes are controlled by thyroid hormone, we studied the effect of thyroid hormone deprivation and administration on the expression of reelin and dab1. As shown by Northern analysis, in situ hybridization, and immunohistochemistry studies, hypothyroid rats expressed decreased levels of reelin RNA and protein during the perinatal period [embryonic day 18 (E18) and postnatal day 0 (P0)]. The effect was evident in Cajal-Retzius cells of cortex layer I, as well as in layers V/VI, hippocampus, and granular neurons of the cerebellum. At later ages, however, Reelin was more abundant in the cortex, hippocampus, cerebellum, and olfactory bulb of hypothyroid rats (P5), and no differences were detected at P15. Conversely, Dab1 levels were higher at P0, and lower at P5 in hypothyroid animals. In line with these results, reelin RNA and protein levels were higher in cultured hippocampal slices from P0 control rats compared to those from hypothyroid animals. Significantly, thyroid-dependent regulation of reelin and dab1 was confirmed in vivo and in vitro by hormone treatment of hypothyroid rats and organotypic cultures, respectively. In both cases, thyroid hormone led to an increase in reelin expression. Our data suggest that the effects of thyroid hormone on neuronal migration may be in part mediated through the control of reelin and dab1 expression during brain ontogenesis.

Animals↗
PubMed1999

Reelin regulates the development and synaptogenesis of the layer-specific entorhino-hippocampal connections.

Here we examine the role of Reelin, an extracellular protein involved in neuronal migration, in the formation of hippocampal connections. Both at prenatal and postnatal stages, the general laminar and topographic distribution of entorhinal projections is preserved in the hippocampus of reeler mutant mice, in the absence of Reelin. However, developing and adult entorhinal afferents show severe alterations, including increased numbers of misrouted fibers and the formation of abnormal patches of termination from the medial and lateral entorhinal cortices. At perinatal stages, single entorhinal axons in reeler mice are grouped into thick bundles, and they have decreased axonal branching and decreased extension of axon collaterals. We also show that the number of entorhino-hippocampal synapses is lower in reeler mice than in control animals during development. Studies performed in mixed entorhino-hippocampal co-cultures combining slices from reeler and wild-type mice indicate that these abnormalities are caused by the lack of Reelin in the target hippocampus. These findings imply that Reelin fulfills a modulatory role during the formation of layer-specific and topographic connections in the hippocampus. They also suggest that Reelin promotes maturation of single fibers and synaptogenesis by entorhinal afferents.

Animals↗
PubMed1999

Role of DNA 5-methylcytosine transferase in cell transformation by fos.

The Fos and Jun oncoproteins form dimeric complexes that stimulate transcription of genes containing activator protein-1 regulatory elements. We found, by representational difference analysis, that expression of DNA 5-methylcytosine transferase (dnmt1) in fos-transformed cells is three times the expression in normal fibroblasts and that fos-transformed cells contain about 20 percent more 5-methylcytosine than normal fibroblasts. Transfection of the gene encoding Dnmt1 induced morphological transformation, whereas inhibition of dnmt1 expression or activity resulted in reversion of fos transformation. Inhibition of histone deacetylase, which associates with methylated DNA, also caused reversion. These results suggest that fos may transform cells through alterations in DNA methylation and in histone deacetylation.

5-Methylcytosine↗
PubMed1999

Medial temporal lobe activation during episodic encoding and retrieval: a PET study.

Recent neuroimaging studies have obtained evidence of activation in the medial temporal lobe (MTL) during episodic encoding and retrieval. On the basis of a meta-analysis of MTL activations in studies that used positron emission tomography (PET), Lepage et al. (Hippocampus 1998;8:313-322) suggested that episodic encoding tends to involve the anterior MTL, whereas episodic retrieval tends to involve the posterior MTL. In a meta-analysis of studies that used PET and functional magnetic resonance imaging, Schacter and Wagner (Hippocampus 1999;9:7-24) reported weaker evidence for such a rostrocaudal distribution of encoding and retrieval activations. However, these meta-analyses were based largely on studies that examined encoding or retrieval separately. Here, we report a direct, within-subjects comparison of MTL activation during episodic encoding and retrieval by using PET. Results indicated that both encoding and retrieval were associated with blood flow increases in similar MTL regions with little indication that encoding and retrieval are preferentially associated with activity in the anterior versus the posterior MTL. Direct comparisons revealed greater blood flow increases in posterior MTL during encoding than retrieval.

Adult↗
PubMed1999

Cross-modal priming and explicit memory in patients with verbal production deficits.

Implicit memory is often thought to reflect an influence of past experience on perceptual processes, yet priming effects are found when the perceptual format of stimuli changes between study and test episodes. Such cross-modal priming effects have been hypothesized to depend upon stimulus recoding processes whereby a stimulus presented in one modality is converted to other perceptual formats. The present research examined recoding accounts of cross-modal priming by testing patients with verbal production deficits that presumably impair the conversion of visual words into auditory/phonological forms. The patients showed normal priming in a visual stem completion task following visual study (Experiment 1), but showed impairments following auditory study in both implicit (Experiment 2) and explicit (Experiment 3) stem completion. The results are consistent with the hypothesis that verbal production processes contribute to the recoding of visual stimuli and support cross-modal priming. The results also indicate that shared processes contribute to both explicit memory and cross-modal implicit memory.

Aged↗
PubMed1999

The electrophysiology of incidental and intentional retrieval: ERP old/new effects in lexical decision and recognition memory.

Event-related brain potentials (ERPs), recorded from a 128-sensor array were used to differentiate brain processes associated with intentional vs incidental memory retrieval. Two experiments examined ERP differences between old (studied) and new (non-studied) words and pseudowords while subjects performed either a recognition memory task or lexical decision task. Previous research has related a P600 old/new effect to the recollection of details, and the present experiments show that this effect was not amplified by intentional retrieval. The P600 effect was larger for words than pseudowords. An earlier (300 to 500 ms), frontally maximal, N400-like old/new effect ('FN400') was similar for words and pseudowords. A third, previously unidentified, mid-frontal, old/new effect was associated with only pseudoword recognition from 300 to 500 ms. Results are discussed with respect to dual-process theories of recognition memory.

Adult↗
PubMed1999

Reelin is a ligand for lipoprotein receptors.

A signaling pathway involving the extracellular protein Reelin and the intracellular adaptor protein Disabled-1 (Dab1) controls cell positioning during mammalian brain development. Here, we demonstrate that Reelin binds directly to lipoprotein receptors, preferably the very low-density lipoprotein receptor (VLDLR) and apolipoprotein E receptor 2 (ApoER2). Binding requires calcium, and it is inhibited in the presence of apoE. Furthermore, the CR-50 monoclonal antibody, which inhibits Reelin function, blocks the association of Reelin with VLDLR. After binding to VLDLR on the cell surface, Reelin is internalized into vesicles. In dissociated neurons, apoE reduces the level of Reelin-induced tyrosine phosphorylation of Dab1. These data suggest that Reelin directs neuronal migration by binding to VLDLR and ApoER2.

Animals↗
PubMed1998

A gene expression approach to mapping the functional maturation of the hippocampus.

Previous studies have shown an association among seizures, neuronal death and the expression of cellular immediate-early genes (cIEG). To understand further the relationship between these processes, we investigated the ability of kainic acid (KAI) to induce behavioral responses and gene expression in the hippocampus of developing fos-lacZ transgenic mice. Despite the fact that KAI elicited seizure-like activity from P2 onwards, Fos-lacZ was first detected at P5 in CA3 pyramidal neurons. Thus, intense behavioral responses were not invariably associated with fos-lacZ expression. Furthermore, while adult CA3 neurons are highly susceptible to KAI toxicity, they are resistant at P5. Therefore, the presence of Fos-lacZ in CA3 neurons is not necessarily predictive of their fate. By P10, Fos-lacZ was induced in CA3 neurons and in the most mature granule neurons of the dentate gyrus (DG). Between P15 and P20, KAI induced fos-lacZ in all CA1 and CA3 pyramidal neurons and most granule neurons of the DG. This stereotypical pattern of fos-lacZ expression mirrors the ontogeny of hippocampal circuitry and glutamate signalling. Thus the fos-lacZ mice can be used to map the functional maturation of the nervous system with single cell resolution. The scope of this approach was extended by administration of additional chemoconvulsants to fos-lacZ mice and by analysis of fos-lacZ transgenic mice with mutations in their FAP site. These additional studies revealed anatomical and mechanistic differences in glutamate receptor-mediated transcriptional responses in the nervous system.

Animals↗
PubMed1998

Regional and cellular patterns of reelin mRNA expression in the forebrain of the developing and adult mouse.

The reelin gene encodes an extracellular protein that is crucial for neuronal migration in laminated brain regions. To gain insights into the functions of Reelin, we performed high-resolution in situ hybridization analyses to determine the pattern of reelin expression in the developing forebrain of the mouse. We also performed double-labeling studies with several markers, including calcium-binding proteins, GAD65/67, and neuropeptides, to characterize the neuronal subsets that express reelin transcripts. reelin expression was detected at embryonic day 10 and later in the forebrain, with a distribution that is consistent with the prosomeric model of forebrain regionalization. In the diencephalon, expression was restricted to transverse and longitudinal domains that delineated boundaries between neuromeres. During embryogenesis, reelin was detected in the cerebral cortex in Cajal-Retzius cells but not in the GABAergic neurons of layer I. At prenatal stages, reelin was also expressed in the olfactory bulb, and striatum and in restricted nuclei in the ventral telencephalon, hypothalamus, thalamus, and pretectum. At postnatal stages, reelin transcripts gradually disappeared from Cajal-Retzius cells, at the same time as they appeared in subsets of GABAergic neurons distributed throughout neocortical and hippocampal layers. In other telencephalic and diencephalic regions, reelin expression decreased steadily during the postnatal period. In the adult, there was prominent expression in the olfactory bulb and cerebral cortex, where it was restricted to subsets of GABAergic interneurons that co-expressed calbindin, calretinin, neuropeptide Y, and somatostatin. This complex pattern of cellular and regional expression is consistent with Reelin having multiple roles in brain development and adult brain function.

Age Factors↗
PubMed1998

Absence of thyroid hormone receptor beta-retinoid X receptor interactions in auditory function and in the pituitary-thyroid axis.

THYROID hormone receptor beta-deficient (TRbeta-/-) mice have defective auditory-evoked brain stem responses (ABR). Since in vitro, TRbeta binds to DNA as homodimers or as heterodimers with retinoid X receptors (RXRs), we investigated whether the TRbeta-/- phenotype may reflect loss of RXR-TRbeta heterodimer or TRbeta homodimer function. Normal ABR thresholds were recorded in RXRbeta-/-, RXRgamma-/-, RXRalpha-/+ and RXR compound mutant mice. When RXR mutations were introduced onto TRbeta-/+ or TRbeta-/- backgrounds, thresholds were dictated solely by TRbeta and not RXR genotype. TRbeta-/-mice also over-produce thyroid hormones and thyroid stimulating hormone; however, levels of these hormones were unaltered by RXR mutations. This suggests that, contrary to in vitro models, RXRs may be dispensable and that TRbeta may function in vivo by an RXR-independent mechanism in the auditory system and pituitary-thyroid axis.

Acoustic Stimulation↗
PubMed1998

Thalamic deactivation during early implicit sequence learning: a functional MRI study.

Previous research has implicated the striatum in implicit sequence learning. However, imaging findings have been inconsistent with regard to activity within the thalamus during performance of such tasks. Contemporary models of cortico-striato-thalamic circuitry suggest opposing influences on thalamic activity; suppression of thalamic activity is mediated by the indirect pathway and enhancement is mediated by the direct pathway. Using functional magnetic resonance imaging, we studied activity within human thalamus during early and late phases of an implicit sequence learning task known to reliably recruit the striatum. Significant deactivation (decreased signal relative to a baseline condition) was observed within the thalamus during early implicit learning. This finding is consistent with models of cortico-striato-thalamic function and specifically supports a profile of early 'thalamic gating' via the indirect pathway.

Basal Ganglia↗
PubMed1998

Reeler: new tales on an old mutant mouse.

Neurological mouse mutants provide an opportunity to dissect the complex mechanisms that underlie vertebrate brain development. Advances in genetic technologies have permitted the identification of genes disrupted in many mutants, allowing a molecular interpretation of the phenotypes. For several decades, the spontaneous mutant mouse reeler has been used as a model for the analysis of the development of laminated brain structures. In this ataxic mutant, the migration of many neurons is aberrant, resulting in disrupted cellular organization. Recently, reelin, the gene disrupted in the reeler mouse, has been identified, reelin encodes a novel extracellular molecule that controls neural cell positioning through mechanisms that are not yet completely understood. Analysis of the expression pattern and the properties of the reelin gene product (Reelin) suggests models for its function during brain development. Furthermore, the recent identification of genes that may function in the Reelin signaling pathway advances our knowledge of the molecular basis of neuronal migration.

Animals↗