Neuregulin-1β modulates in vivo entorhinal–hippocampal synaptic transmission in adult rats

Roysommuti, Sanya; Carroll, Steven L.; Wyss, J. Michael

doi:10.1016/s0306-4522(03)00503-7

Cited by 38 publications

(23 citation statements)

References 40 publications

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“…262 The large number of NRG1 signalling mechanisms and isoforms parallel the range of its functional effects. 258,260,[263][264][265][266] These include neuronal and glial functions implicated in schizophrenia, ranging from development (eg neuronal migration, axon guidance, synaptogenesis, glial differentiation, myelination), to neurotransmission and synaptic plasticity (eg recruitment of nicotinic, GABA, and NMDA receptors, long-term potentiation). It is a reasonable if vague working hypothesis that the genetic risk for schizophrenia associated with NRG1 is mediated by a molecular 'bottleneck' in NRG1 signalling that alters, probably to a small degree and in a temporally, spatially, and isoform-limited fashion, the efficiency of NRG1 effects on neural development and plasticity.…”

Section: à6mentioning

confidence: 99%

Schizophrenia genes, gene expression, and neuropathology: on the matter of their convergence

2004

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This review critically summarizes the neuropathology and genetics of schizophrenia, the relationship between them, and speculates on their functional convergence. The morphological correlates of schizophrenia are subtle, and range from a slight reduction in brain size to localized alterations in the morphology and molecular composition of specific neuronal, synaptic, and glial populations in the hippocampus, dorsolateral prefrontal cortex, and dorsal thalamus. These findings have fostered the view of schizophrenia as a disorder of connectivity and of the synapse. Although attractive, such concepts are vague, and differentiating primary events from epiphenomena has been difficult. A way forward is provided by the recent identification of several putative susceptibility genes (including neuregulin, dysbindin, COMT, DISC1, RGS4, GRM3, and G72). We discuss the evidence for these and other genes, along with what is known of their expression profiles and biological roles in brain and how these may be altered in schizophrenia. The evidence for several of the genes is now strong. However, for none, with the likely exception of COMT, has a causative allele or the mechanism by which it predisposes to schizophrenia been identified. Nevertheless, we speculate that the genes may all converge functionally upon schizophrenia risk via an influence upon synaptic plasticity and the development and stabilization of cortical microcircuitry. NMDA receptor-mediated glutamate transmission may be especially implicated, though there are also direct and indirect links to dopamine and GABA signalling. Hence, there is a correspondence between the putative roles of the genes at the molecular and synaptic levels and the existing understanding of the disorder at the neural systems level. Characterization of a core molecular pathway and a 'genetic cytoarchitecture' would be a profound advance in understanding schizophrenia, and may have equally significant therapeutic implications. Molecular Psychiatry (2005) 10, 40-68.

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Section: à6mentioning

confidence: 99%

Schizophrenia genes, gene expression, and neuropathology: on the matter of their convergence

2004

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“…41 In culture studies, NRG stimulates the generation of neuronal precursors, 42 and radial glia transform into astrocytes only in the presence of NRG1 and its receptor. 43 Further, NRG1 is a likely modulator of neurotransmission in vivo, as Roysommuti et al 44 demonstrated that NRG1 can potentiate glutamate neurotransmission at rat entorhinal-CA1 synapses.…”

Section: Discussionmentioning

confidence: 99%

Neuregulin 1 (8p12) and childhood-onset schizophrenia: susceptibility haplotypes for diagnosis and brain developmental trajectories

Addington¹,

Gornick²,

Shaw³

et al. 2006

Mol Psychiatry

110

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Childhood-onset schizophrenia (COS), defined as onset of psychosis by the age of 12, is a rare and malignant form of the illness, which may have more salient genetic influence. Since the initial report of association between neuregulin 1 (NRG1) and schizophrenia in 2002, numerous independent replications have been reported. In the current study, we genotyped 56 markers (54 single-nucleotide polymorphisms (SNPs) and two microsatellites) spanning the NRG1 locus on 78 COS patients and their parents. We used family-based association analysis for both diagnostic (extended transmission disequilibrium test) and quantitative phenotypes (quantitative transmission disequilibrium test) and mixed-model regression. Most subjects had prospective anatomic brain magnetic resonance imaging (MRI) scans at 2-year intervals. Further, we genotyped a sample of 165 healthy controls in the MRI study to examine genetic risk effects on normal brain development. Individual markers showed overtransmission of alleles to affecteds (P = 0.009-0.05). Further, several novel four-marker haplotypes demonstrated significant transmission distortion. There was no evidence of epistasis with SNPs in erbB4. The risk allele (0) at 420M9-1395 was associated with poorer premorbid social functioning. Further, possession of the risk allele was associated with different trajectories of change in lobar volumes. In the COS group, risk allele carriers had greater total gray and white matter volume in childhood and a steeper rate of subsequent decline in volume into adolescence. By contrast, in healthy children, possession of the risk allele was associated with different trajectories in gray matter only and was confined to frontotemporal regions, reflecting epistatic or other illness-specific effects mediating NRG1 influence on brain development in COS. This replication further documents the role of NRG1 in the abnormal brain development in schizophrenia. This is the first demonstration of a disease-specific pattern of gene action in schizophrenia.

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“…In the prefrontal cortex, NRG 1␤ reduces NMDA currents by enhancing NR1 internalization (Gu et al, 2005). Other rapid NRG 1 actions include increase of calcium-activated potassium channels (Chae et al, 2005) and modulating in vivo entorhinal-hippocampal synaptic transmission (Roysommuti et al, 2003).…”

Section: Discussionmentioning

confidence: 99%

An Acute Effect of Neuregulin 1β to Suppress α7-Containing Nicotinic Acetylcholine Receptors in Hippocampal Interneurons

Chang¹,

Fischbach²

2006

J. Neurosci.

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We examined rapid effects of neuregulin (NRG) on nicotinic acetylcholine (ACh) receptors in interneurons located in the stratum radiatum of the hippocampus. Two types of response were detected by whole-cell recordings after brief pulses of ACh. One type was a rapidly rising and falling (monophasic) current that was blocked by methyllycaconitine. The other type was a similar fast response followed by a more slowly rising and falling current. The slow component of the biphasic response was resistant to methyllycaconitine. Perfusion or local application with NRG 1␤ rapidly decreased fast inward ACh currents. NRG 1␤ had no effect on slow responses. NRG

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Neuregulin-1β modulates in vivo entorhinal–hippocampal synaptic transmission in adult rats

Cited by 38 publications

References 40 publications

Schizophrenia genes, gene expression, and neuropathology: on the matter of their convergence

Schizophrenia genes, gene expression, and neuropathology: on the matter of their convergence

Neuregulin 1 (8p12) and childhood-onset schizophrenia: susceptibility haplotypes for diagnosis and brain developmental trajectories

An Acute Effect of Neuregulin 1β to Suppress α7-Containing Nicotinic Acetylcholine Receptors in Hippocampal Interneurons

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