Glutamate Transporters Contribute to the Time Course of Synaptic Transmission in Cerebellar Granule Cells

Overstreet, Linda S.; Kinney, Gregory A.; Liu, Ying Bing; Billups, Daniela; Slater, N. T.

doi:10.1523/jneurosci.19-21-09663.1999

Cited by 90 publications

(86 citation statements)

References 68 publications

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“…In addition, maturation of glutamate reuptake would almost certainly influence the decay kinetics of glutamate receptors (Overstreet et al, 1999), whereas we show that AMPA decay remains constant throughout maturation in all cell types (Fig. 4).…”

Section: Underlying Mechanisms For Increases In the Ampa:nmda Ratiomentioning

confidence: 64%

Functional Maturation of the First Synapse in Olfaction: Development and Adult Neurogenesis

Grubb

Nissant²,

Murray³

et al. 2008

J. Neurosci.

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The first synapse in olfaction undergoes considerable anatomical plasticity in both early postnatal development and adult neurogenesis, yet we know very little concerning its functional maturation at these times. Here, we used whole-cell recordings in olfactory bulb slices to describe olfactory nerve inputs to developing postnatal neurons and to maturing adult-born cells labeled with a GFP-encoding lentivirus. In both postnatal development and adult neurogenesis, the maturation of olfactory nerve synapses involved an increase in the relative contribution of AMPA over NMDA receptors, and a decrease in the contribution of NMDA receptors containing the NR2B subunit. These postsynaptic transformations, however, were not mirrored by presynaptic changes: in all cell groups, paired-pulse depression remained constant as olfactory nerve synapses matured. Although maturing cells may therefore offer, transiently, a functionally distinct connection for inputs from the nose, presynaptic function at the first olfactory connection remains remarkably constant in the face of considerable anatomical plasticity.

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Section: Underlying Mechanisms For Increases In the Ampa:nmda Ratiomentioning

confidence: 64%

Functional Maturation of the First Synapse in Olfaction: Development and Adult Neurogenesis

Grubb

Nissant²,

Murray³

et al. 2008

J. Neurosci.

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“…For example, the glutamate transporter, EAAT4, is highly enriched on Purkinje cell spines (66) where it is thought to modulate postsynaptic excitation (67,68). Similarly, EAAC1 is associated with dendritic spines and shafts in the CA1 region of the hippocampus (57).…”

Section: Discussionmentioning

confidence: 99%

Activation of Metabotropic Glutamate Receptor mGlu5 on Nuclear Membranes Mediates Intranuclear Ca2+ Changes in Heterologous Cell Types and Neurons

O’Malley

Jong

Gonchar

et al. 2003

Journal of Biological Chemistry

121

116

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Nuclear Ca2؉ plays a critical role in many cellular functions although its mode (s) of regulation is unclear. This study shows that the metabotropic glutamate receptor, mGlu5, mobilizes nuclear Ca 2؉ independent of cytosolic Ca 2؉ regulation. Immunocytochemical, ultrastructural, and subcellular fractionation techniques revealed that the metabotropic glutamate receptor, mGlu5, can be localized to nuclear membranes in heterologous cells as well as midbrain and cortical neurons. Changes in nuclear Ca2ϩ play an integral role in cellular functions such as protein import, apoptosis, and gene transcription (1, 2). Nuclear Ca 2ϩ may be generated from a number of sources including diffusion of cytosolic Ca 2ϩ waves through nuclear pore complexes (2). Because the outer nuclear envelope is continuous with the endoplasmic reticulum, which serves as an internal store of Ca 2ϩ , rises in nuclear Ca 2ϩ may also be attributable to a luminal source (3). Recent studies using high speed imaging of intracellular Ca 2ϩ have shown that waves of Ca 2ϩ can invade the nucleus by emptying intracellular stores (4). Calcium release from internal stores is controlled by various channels including the inositol 1,4,5-trisphosphate (IP 3 ) 1 receptor and ryanodine receptor families (5, 6) both of which are present on nuclear membranes (7,8). Calcium itself is an activator of these channels (1) although nuclear IP 3 can stimulate IP 3 receptors located on the inner nuclear membrane and cADP ribose has been shown to activate nuclear ryanodine receptors (7,8). Luminal Ca 2ϩ is refilled at least in part by the nuclear Ca 2ϩ -ATPase (9, 10) located on the outer nuclear membrane. Thus, although signals originating at the plasma membrane may be transmitted to the nucleus (4), the presence of specific Ca 2ϩ transporters on the nuclear envelope argues for a nuclear Ca 2ϩ regulatory system that may be independent of cytosolic Ca 2ϩ regulation. Many components of G protein signaling pathways are also found in the nucleus or associated with nuclear membranes. These include phospholipase C isozymes (11, 12), nuclear inositol phosphates (12, 13), DAG (13), PKC isozymes (14), adenylate cyclase (15), regulators of G protein signaling (RGS proteins; Refs. 16 and 17) as well as heterotrimeric G proteins themselves (18). These observations raise the possibility that plasma membrane-based signaling components may also serve a similar function at nuclear membranes. Indeed, several recent reports are consistent with the notion that nuclear G protein-coupled receptors directly modulate nuclear signal transduction pathways. For example, angiotensin II receptors were found on hepatocyte nuclear membranes (19), opioid binding sites were described on ventricular myocardial nuclei (20) and endothelin-1 receptors were reported on vascular smooth muscle nuclear membranes (21). Direct evidence of nuclear receptor G protein signaling has also been demonstrated for prostaglandin receptors which, when stimulated, cause rapid Ca 2ϩ influx into the nucleus (22,23). Taken togeth...

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“…Previous studies that used the electrophysiological method have shown that inhibition of GT activity may not prolong significantly the single stimulus-induced excitatory postsynaptic glutamate-mediated currents, but it does so if the stimulus is repetitive and excessive (Overstreet et al, 1999), a condition that is encountered after peripheral nerve injury (Wall et al, 1974;Seltzer et al, 1991). In this regard, enhancing GT uptake activity by the positive GT activity regulator riluzole would be expected to reduce glutamate excitation regardless of changes in GT expression.…”

Section: Possible Mechanisms Of Gt Changes After CCImentioning

confidence: 99%

Altered Expression and Uptake Activity of Spinal Glutamate Transporters after Nerve Injury Contribute to the Pathogenesis of Neuropathic Pain in Rats

2003

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The central glutamatergic system has been implicated in the pathogenesis of neuropathic pain, and a highly active central glutamate transporter (GT) system regulates the uptake of endogenous glutamate. Here we demonstrate that both the expression and uptake activity of spinal GTs changed after chronic constriction nerve injury (CCI) and contributed to neuropathic pain behaviors in rats. CCI induced an initial GT upregulation up to at least postoperative day 5 primarily within the ipsilateral spinal cord dorsal horn, which was followed by a GT downregulation when examined on postoperative days 7 and 14 by Western blot and immunohistochemistry. Intrathecal administration of the tyrosine kinase receptor inhibitor K252a and the mitogen-activated protein kinase inhibitor PD98059 for postoperative days 1-4 reduced and nearly abolished the initial GT upregulation in CCI rats, respectively. Prevention of the CCI-induced GT upregulation by PD98059 resulted in exacerbated thermal hyperalgesia and mechanical allodynia reversible by the noncompetitive NMDA receptor antagonist MK-801, indicating that the initial GT upregulation hampered the development of neuropathic pain behaviors. Moreover, CCI significantly reduced glutamate uptake activity of spinal GTs when examined on postoperative day 5, which was prevented by riluzole (a positive GT activity regulator) given intrathecally twice a day for postoperative days 1-4. Consistently, riluzole attenuated and gradually reversed neuropathic pain behaviors when the 4 d riluzole treatment was given for postoperative days 1-4 and 5-8, respectively. These results indicate that changes in the expression and glutamate uptake activity of spinal GTs may play a critical role in both the induction and maintenance of neuropathic pain after nerve injury via the regulation of regional glutamate homeostasis, a new mechanism relevant to the pathogenesis of neuropathic pain.

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Glutamate Transporters Contribute to the Time Course of Synaptic Transmission in Cerebellar Granule Cells

Cited by 90 publications

References 68 publications

Functional Maturation of the First Synapse in Olfaction: Development and Adult Neurogenesis

Functional Maturation of the First Synapse in Olfaction: Development and Adult Neurogenesis

Activation of Metabotropic Glutamate Receptor mGlu5 on Nuclear Membranes Mediates Intranuclear Ca2+ Changes in Heterologous Cell Types and Neurons

Altered Expression and Uptake Activity of Spinal Glutamate Transporters after Nerve Injury Contribute to the Pathogenesis of Neuropathic Pain in Rats

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