Neuregulin links dopaminergic and glutamatergic neurotransmission to control hippocampal synaptic plasticity

Neddens, Joerg; Vullhorst, Detlef; Paredes, Daniel; Buonanno, Andrés

doi:10.4161/cib.2.3.7825

Cited by 22 publications

(13 citation statements)

References 53 publications

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“…20,22 However, the nature of NRG1 activity on dopaminergic development or function is still poorly understood. 23 In this study, we have designed an experimental protocol based on the neurodevelopmental hypothesis of schizophrenia [24][25][26] and assessed the pathological roles of excess NRG1 signals on dopaminergic neurons and their functions during and after development. 27 As upregulation of type-1 NRG1 expression is reported in schizophrenia brain pathology, 4,5 we selected this isoform of NRG1 protein and administered it to the periphery of mouse pups.…”

Section: Introductionmentioning

confidence: 99%

Transient exposure of neonatal mice to neuregulin-1 results in hyperdopaminergic states in adulthood: implication in neurodevelopmental hypothesis for schizophrenia

et al. 2010

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Neuregulin-1 (NRG1) is implicated in the etiology or pathology of schizophrenia, although its biological roles in this illness are not fully understood. Human midbrain dopaminergic neurons highly express NRG1 receptors (ErbB4). To test its neuropathological role in the neurodevelopmental hypothesis of schizophrenia, we administered type-1 NRG1 protein to neonatal mice and evaluated the immediate and subsequent effects on dopaminergic neurons and their associated behaviors. Peripheral NRG1 administration activated midbrain ErbB4 and elevated the expression, phosphorylation and enzyme activity of tyrosine hydroxylase (TH), which ultimately increased dopamine levels. The hyperdopaminergic state was sustained in the medial prefrontal cortex after puberty. There were marked increases in dopaminergic terminals and TH levels. In agreement, higher amounts of dopamine were released from this brain region of NRG1-treated mice following high potassium stimulation. Furthermore, NRG1-treated mice exhibited behavioral impairments in prepulse inhibition, latent inhibition, social behaviors and hypersensitivity to methamphetamine. However, there were no gross abnormalities in brain structures or other phenotypic features of neurons and glial cells. Collectively, our findings provide novel insights into neurotrophic contribution of NRG1 to dopaminergic maldevelopment and schizophrenia pathogenesis.

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Section: Introductionmentioning

confidence: 99%

Transient exposure of neonatal mice to neuregulin-1 results in hyperdopaminergic states in adulthood: implication in neurodevelopmental hypothesis for schizophrenia

et al. 2010

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“…Recent studies suggest that Erbb4 is expressed exclusively in interneurons and not at all in excitatory neurons (Vullhorst et al, 2009; Fazzari et al, 2010). At the subcellular level, Erbb4 was shown to be in axonal terminals of interneurons by electron microscopy or immunofluorescence staining (Fazzari et al, 2010; Woo et al, 2007) although this notion was challenged (Neddens and Buonanno, 2011; Neddens et al, 2009). Erbb4 has also been found on the postsynaptic site of excitatory and inhibitory synapses in GABAergic interneurons (Fazzari et al, 2010; Huang et al, 2001; Krivosheya et al, 2008; Vullhorst et al, 2009; Woo et al, 2007) (Figure 3).…”

Section: Assembly Of Neuronal Circuitrymentioning

confidence: 99%

Neuregulin-ERBB Signaling in the Nervous System and Neuropsychiatric Diseases

Mei

Nave

2014

Neuron

508

464

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Summary Neuregulins (NRGs) comprise a large family of growth factors that stimulate ERBB receptor tyrosine kinases. NRGs and their receptors ERBBs have been identified as susceptibility genes for diseases such as schizophrenia (SZ) and bipolar disorder. Recent studies have revealed complex Nrg/Erbb signaling networks that regulate the assembly of neural circuitry, myelination, neurotransmission and synaptic plasticity. Evidence indicates there is an optimal level of NRG/ERBB signaling in the brain and deviation from it impairs brain functions. NRGs/ERBBs and downstream signaling pathways may provide therapeutic targets for specific neuropsychiatric symptoms.

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“…Nrg1 signaling is important in nervous system development contributing to aspects of neuronal migration, synaptogenesis, gliogenesis, and neuron-glia communication (Taveggia et al, 2005;Lopez-Bendito et al, 2006;Quintes et al, 2010;Ting et al, 2011). In mature animals, alterations in Nrg1/ErbB signaling are manifest in aberrant peripheral myelination, and deficits in synaptic plasticity in hippocampal and cortical slices (Michailov et al, 2004;Bjarnadottir et al, 2007;Li et al, 2007;Brinkmann et al, 2008;Chen et al, 2008b;Pitcher et al, 2011;Shamir et al, 2012). Likewise, Nrg1 and ErbB receptor interactions have been shown to affect the synaptic function of many neuronal transmitter receptors, including glutamate ␣-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) receptors, N-methyl-D-aspartate (NMDA) receptors, and nicotinic acetylcholine receptors (nAChRs) Bjarnadottir et al, 2007;Zhong et al, 2008;Abe et al, 2011;Canetta et al, 2011;Pitcher et al, 2011;Ting et al, 2011;Fenster et al, 2012).…”

Section: Introductionmentioning

confidence: 99%

“…Type III Nrg1 is expressed in the basolateral nucleus of the amygdala (BLA) and in cortical neurons that project to the BLA (see below), and ErbB4 is expressed in interneu-rons within the BLA as well as highly expressed in the basomedial area (Shamir et al, 2012). The BLA receives extensive cholinergic input from the nucleus basalis of Meynert (Carlsen et al, 1985;Wenk, 1997;Schafer et al, 1998;Muller et al, 2011). Both ␣7* and non ␣7* nAChRs have been shown to contribute to presynaptic modulation of cortical-BLA synapses by exogenously applied nicotine (Jiang and Role, 2008).…”

Section: Introductionmentioning

confidence: 99%

Type III Neuregulin 1 Is Required for Multiple Forms of Excitatory Synaptic Plasticity of Mouse Cortico-Amygdala Circuits

Jiang

Emmetsberger

Talmage

et al. 2013

Journal of Neuroscience

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The amygdala plays an important role in the formation and storage of memories associated with emotional events. The cortical glutamatergic inputs onto pyramidal neurons in the basolateral nucleus of the amygdala (BLA) contribute to this process. As the interaction between neuregulin 1 (Nrg1) and its ErbB receptors has been implicated in the pathological mechanisms of schizophrenia, loss of Nrg1 may disrupt cortical-amygdala neural circuits, resulting in altered processing of salient memories. Here we show that Nrg1 is critical in multiple forms of plasticity of cortical projections to pyramidal neurons of the BLA. The miniature EPSCs in Nrg1 heterozygous animals have a faster time constant of decay and evoked synaptic currents have a smaller NMDA/AMPA ratio than those recorded in wild-type (WT) littermates. Both high-frequency electrical stimulation of cortical inputs and burst stimulation combined with nicotine exposure results in long-lasting potentiation in WT animals. However, the same manipulations have little to no effect on glutamatergic synaptic plasticity in the BLA from Nrg1 heterozygous mice. Comparison of WT, Nrg1 heterozygous animals and ␣7 nicotinic receptor heterozygous mice reveals that the sustained phase of potentiation of glutamatergic transmission after burst stimulation with or without nicotine only occurs in the WT mice. Together, these findings support the idea that type III Nrg1 is essential to multiple aspects of the modulation of excitatory plasticity at cortical-BLA synapses.

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Neuregulin links dopaminergic and glutamatergic neurotransmission to control hippocampal synaptic plasticity

Cited by 22 publications

References 53 publications

Transient exposure of neonatal mice to neuregulin-1 results in hyperdopaminergic states in adulthood: implication in neurodevelopmental hypothesis for schizophrenia

Transient exposure of neonatal mice to neuregulin-1 results in hyperdopaminergic states in adulthood: implication in neurodevelopmental hypothesis for schizophrenia

Neuregulin-ERBB Signaling in the Nervous System and Neuropsychiatric Diseases

Type III Neuregulin 1 Is Required for Multiple Forms of Excitatory Synaptic Plasticity of Mouse Cortico-Amygdala Circuits

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