GluN2B-Containing NMDA Receptors Promote Wiring of Adult-Born Neurons into Olfactory Bulb Circuits

Kelsch, Wolfgang; Li, Zhijun; Eliava, Marina; Goengrich, Christina; Monyer, Hannah

doi:10.1523/jneurosci.1459-12.2012

Cited by 37 publications

(26 citation statements)

References 35 publications

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“…Spine density in the proximal compartment of adult-born GCs peaks at 15-30 d before further pruning at 90 dpi (29). Moreover, impairing NMDA receptors decreases the proximal spine density but sensory deprivation distinctly alters proximal and basal domains (22,31). Collectively, these data indicate that sensory experience strongly influences the direction and location of structural synaptic plasticity.…”

Section: Discussionmentioning

confidence: 84%

Olfactory learning promotes input-specific synaptic plasticity in adult-born neurons

Lepousez

Nissant

Bryant

et al. 2014

Proc. Natl. Acad. Sci. U.S.A.

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The production of new neurons in the olfactory bulb (OB) through adulthood is a major mechanism of structural and functional plasticity underlying learning-induced circuit remodeling. The recruitment of adult-born OB neurons depends not only on sensory input but also on the context in which the olfactory stimulus is received. Among the multiple steps of adult neurogenesis, the integration and survival of adult-born neurons are both strongly influenced by olfactory learning. Conversely, optogenetic stimulation of adultborn neurons has been shown to specifically improve olfactory learning and long-term memory. However, the nature of the circuit and the synaptic mechanisms underlying this reciprocal influence are not yet known. Here, we showed that olfactory learning increases the spine density in a region-restricted manner along the dendritic tree of adult-born granule cells (GCs). Anatomical and electrophysiological analysis of adult-born GCs showed that olfactory learning promotes a remodeling of both excitatory and inhibitory inputs selectively in the deep dendritic domain. Circuit mapping revealed that the malleable dendritic portion of adult-born neurons receives excitatory inputs mostly from the regions of the olfactory cortex that project back to the OB. Finally, selective optogenetic stimulation of olfactory cortical projections to the OB showed that learning strengthens these inputs onto adult-born GCs. We conclude that learning promotes input-specific synaptic plasticity in adult-born neurons, which reinforces the top-down influence from the olfactory cortex to early stages of olfactory information processing.sensory systems | inhibitory circuits | piriform cortex | cortico-bulbar projections | glutamate

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Section: Discussionmentioning

confidence: 84%

Olfactory learning promotes input-specific synaptic plasticity in adult-born neurons

Lepousez

Nissant

Bryant

et al. 2014

Proc. Natl. Acad. Sci. U.S.A.

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“…NMDAR-mediated currents are prominent in several neuronal populations, including maturing cortical pyramidal cells 26 , olfactory granule cells 27 and hippocampal interneurons 28 . To dissect the receptor composition of thalamic and intracortical synapses, we used a Rosa26 LSL.ChR.EYFP line in combination with either Emx1 Cre and Bhlhb5 Cre driver lines, which exclusively target excitatory cortical neurons, or a VGlut2 Cre driver line, which preferentially (but not exclusively) induces recombination in thalamic neurons (hereafter Emx1-ChR2 and VGlut2-ChR2 , respectively) (Fig.…”

Section: Resultsmentioning

confidence: 99%

Sensory inputs control the integration of neurogliaform interneurons into cortical circuits

et al. 2015

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Neuronal microcircuits in the superficial layers of the mammalian cortex provide the substrate for associative cortical computation. Inhibitory interneurons constitute an essential component of the circuitry and are fundamental to the integration of local and long-range information. Here we report that, during early development, superficially positioned Reelin-expressing neurogliaform interneurons in the mouse somatosensory cortex receive afferent innervation from both cortical and thalamic excitatory sources. Attenuation of ascending sensory, but not intracortical, excitation leads to axo-dendritic morphological defects in these interneurons. Moreover, abrogation of the NMDA receptors through which the thalamic inputs signal results in a similar phenotype, as well as in the selective loss of thalamic and a concomitant increase in intracortical connectivity. These results suggest that thalamic inputs are critical in determining the balance between local and long-range connectivity and are fundamental to the proper integration of Reelin-expressing interneurons into nascent cortical circuits.

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“…The requirement for depolarization and synaptic release of glutamate renders NMDA receptors a trigger for synaptic plasticity, a cellular correlate of learning and memory (Lisman 2003;Huganir and Nicoll, 2013). NMDA receptors participate in the development of the CNS (Colonnese et al, 2005;Colonnese and Constantine-Paton, 2006;Kelsch et al, 2012). In addition, overactivation of NMDA receptors can promote seizures and cell death (Choi, 1994;Rothman and Olney, 1995;Obrenovitch et al, 1997;Dirnagl et al, 1999;Yurkewicz et al, 2005), and NMDA receptor hypofunction is a leading hypothesis for schizophrenia (Coyle, 2012;Menniti et al, 2013).…”

Section: Gaba/glutamate Receptor Mutations In Neurologic Diseasesmentioning

confidence: 99%

Ionotropic GABA and Glutamate Receptor Mutations and Human Neurologic Diseases

Yuan¹,

Low²,

Moody³

et al. 2015

Mol Pharmacol

186

176

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The advent of whole exome/genome sequencing and the technology-driven reduction in the cost of next-generation sequencing as well as the introduction of diagnostic-targeted sequencing chips have resulted in an unprecedented volume of data directly linking patient genomic variability to disorders of the brain. This information has the potential to transform our understanding of neurologic disorders by improving diagnoses, illuminating the molecular heterogeneity underlying diseases, and identifying new targets for therapeutic treatment. There is a strong history of mutations in GABA receptor genes being involved in neurologic diseases, particularly the epilepsies. In addition, a substantial number of variants and mutations have been found in GABA receptor genes in patients with autism, schizophrenia, and addiction, suggesting potential links between the GABA receptors and these conditions. A new and unexpected outcome from sequencing efforts has been the surprising number of mutations found in glutamate receptor subunits, with the GRIN2A gene encoding the GluN2A N-methyl-D-aspartate receptor subunit being most often affected. These mutations are associated with multiple neurologic conditions, for which seizure disorders comprise the largest group. The GluN2A subunit appears to be a locus for epilepsy, which holds important therapeutic implications. Virtually all a-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor mutations, most of which occur within GRIA3, are from patients with intellectual disabilities, suggesting a link to this condition. Similarly, the most common phenotype for kainate receptor variants is intellectual disability. Herein, we summarize the current understanding of disease-associated mutations in ionotropic GABA and glutamate receptor families, and discuss implications regarding the identification of human mutations and treatment of neurologic diseases.

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GluN2B-Containing NMDA Receptors Promote Wiring of Adult-Born Neurons into Olfactory Bulb Circuits

Cited by 37 publications

References 35 publications

Olfactory learning promotes input-specific synaptic plasticity in adult-born neurons

Olfactory learning promotes input-specific synaptic plasticity in adult-born neurons

Sensory inputs control the integration of neurogliaform interneurons into cortical circuits

Ionotropic GABA and Glutamate Receptor Mutations and Human Neurologic Diseases

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