Glutamate Delta-1 Receptor Regulates Inhibitory Neurotransmission in the Nucleus Accumbens Core and Anxiety-Like Behaviors

Gawande, Dinesh Y.; Shelkar, Gajanan P.; Liu, Jinxu; Ayala, Anna D; Pavuluri, Ratnamala; Choi, Diane; Smith, Yoland; Dravid, Shashank M.

doi:10.1007/s12035-021-02461-3

Cited by 12 publications

(6 citation statements)

References 34 publications

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“…The dysfunction of neurotransmitters in the NAc is related to the NMS of PD, which may support the association between neural network changes in NAc and the NMS in PD. The loss of glutamate delta‐1 receptor leads to reduced inhibitory neurotransmitters of medium spiny neurons in the core of NAc and results in neuropsychiatric disorders, especially anxiety and depression‐like behaviors 44 . The decreased levels of dopamine D2/D3 receptors in NAc may account for the apathy in PD 45 .…”

Section: Discussionmentioning

confidence: 99%

“…The loss of glutamate delta‐1 receptor leads to reduced inhibitory neurotransmitters of medium spiny neurons in the core of NAc and results in neuropsychiatric disorders, especially anxiety and depression‐like behaviors. 44 The decreased levels of dopamine D2/D3 receptors in NAc may account for the apathy in PD. 45 The dysfunction of adenosine A 2A receptors in NAc is relevant to cognitive impairment via modulating dopamine and glutamate homeostasis in PD.…”

Section: Discussionmentioning

confidence: 99%

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Altered functional connectivity of nucleus accumbens subregions associates with non‐motor symptoms in Parkinson's disease

et al. 2022

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Aims This study aimed to identify the functional connectivity (FC) changes of nucleus accumbens (NAc) subregions and characterize the association of network changes and non‐motor symptoms (NMS) in Parkinson's disease (PD). Methods We enrolled 129 PD patients and 106 healthy controls from our center and the PPMI (Parkinson's Progression Markers Initiative) database. The FC of the bilateral core and shell of the NAc were measured and compared between the two groups. We further used partial least squares correlation to reveal the relationships between altered FC of NAc subregions and manifestations of NMS of PD. Results The subregions of left core, left shell, and right core had reduced FC with extensive brain regions in PD patients compared with healthy controls. These three subregions were commonly associated with depression, anxiety, apathy, and cognitive impairment. Moreover, the left core and left shell were associated with excessive daytime sleepiness, whereas the right core was associated with olfactory impairment and rapid eye movement sleep behavior disorder. Conclusion This study for the first time identified the neural network changes of NAc subregions in PD and the associations between network changes and phenotypes of NMS. Our findings provide new insights into the pathogenesis of NMS in PD.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Altered functional connectivity of nucleus accumbens subregions associates with non‐motor symptoms in Parkinson's disease

et al. 2022

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“…Whether neurexins are required for GluD1/Cbln4 signaling at SOM synapses in somatosensory cortex remains untested. Finally, in nucleus accumbens core of ventral striatum, GluD1 loss led to reduced mIPSC amplitude and frequency, density of inhibitory terminals, and inhibitory release probability, suggesting pre- and post-synaptic effects on synaptic transmission ( Gawande et al, 2021 ). Loss of GluD1 in dorsal striatum, however, produced excitatory but not inhibitory deficits, indicating region-specific localization and function of GluD1.…”

Section: Function Of Neurexin Binding Partners At Inhibitory Synapsesmentioning

confidence: 99%

Neurexins and their ligands at inhibitory synapses

Boxer

Aoto

2022

Front. Synaptic Neurosci.

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Since the discovery of neurexins (Nrxns) as essential and evolutionarily conserved synaptic adhesion molecules, focus has largely centered on their functional contributions to glutamatergic synapses. Recently, significant advances to our understanding of neurexin function at GABAergic synapses have revealed that neurexins can play pleiotropic roles in regulating inhibitory synapse maintenance and function in a brain-region and synapse-specific manner. GABAergic neurons are incredibly diverse, exhibiting distinct synaptic properties, sites of innervation, neuromodulation, and plasticity. Different classes of GABAergic neurons often express distinct repertoires of Nrxn isoforms that exhibit differential alternative exon usage. Further, Nrxn ligands can be differentially expressed and can display synapse-specific localization patterns, which may contribute to the formation of a complex trans-synaptic molecular code that establishes the properties of inhibitory synapse function and properties of local circuitry. In this review, we will discuss how Nrxns and their ligands sculpt synaptic inhibition in a brain-region, cell-type and synapse-specific manner.

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“…Either GluD1 R or GluD2 R is expressed in the central neurons in nearly every region of the adult mouse brain, with a high level of overlap at the regional and cellular level (Konno et al , 2014; Hepp et al , 2015; Nakamoto et al , 2020). Predominately, GluD1 R and GluD2 R are found in postsynaptic specializations on the dendrites and spines (Landsend et al , 1997; Hepp et al , 2015; Nakamoto et al , 2020; Hoover et al , 2021), where they regulate synapse formation, composition, and autophagy in complex with trans‐synaptic and secreted proteins (Tao et al , 2018; Fossati et al , 2019; Dai et al , 2021; Gawande et al , 2021, 2022). The study of ion channel function of GluD1 R has been limited since there is no known agonist that binds to GluD1 R directly to gate opening of the channel.…”

Section: Introductionmentioning

confidence: 99%

Potentiation of neuronal activity by tonic GluD1 current in brain slices

Copeland,

Gugel,

Gantz

2023

EMBO Reports

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Ion channel function of native delta glutamate receptors (GluD R ) is incompletely understood. Previously, we and others have shown that activation of Gaq protein-coupled receptors (GqPCR) produces a slow inward current carried by GluD1 R . GluD1 R also carries a tonic cation current of unknown cause. Here, using voltage-clamp electrophysiological recordings from adult mouse brain slices containing the dorsal raphe nucleus, we find no role of ongoing G-proteincoupled receptor activity in generating or sustaining tonic GluD1 R currents. Neither augmentation nor disruption of G protein activity affects tonic GluD1 R currents, suggesting that ongoing G-proteincoupled receptor activity does not give rise to tonic GluD1 R currents. Further, the tonic GluD1 R current is unaffected by the addition of external glycine or D-serine, which influences GluD2 R current at millimolar concentrations. Instead, GqPCR-stimulated and tonic GluD1 R currents are regulated by physiological levels of external calcium. In current-clamp recordings, block of GluD1 R channels hyperpolarizes the membrane by ~7 mV at subthreshold potentials, reducing excitability. Thus, GluD1 R carries a G-protein-independent tonic current that contributes to subthreshold neuronal excitation in the dorsal raphe nucleus.

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Glutamate Delta-1 Receptor Regulates Inhibitory Neurotransmission in the Nucleus Accumbens Core and Anxiety-Like Behaviors

Cited by 12 publications

References 34 publications

Altered functional connectivity of nucleus accumbens subregions associates with non‐motor symptoms in Parkinson's disease

Altered functional connectivity of nucleus accumbens subregions associates with non‐motor symptoms in Parkinson's disease

Neurexins and their ligands at inhibitory synapses

Potentiation of neuronal activity by tonic GluD1 current in brain slices

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