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Full-Text Articles in Neurosciences
Circuit-Specific Control Of The Medial Entorhinal Inputs To The Dentate Gyrus By Atypical Presynaptic Nmdars Activated By Astrocytes, Iaroslav Savtchouk, Maria Amalia Di Castro, Rugina Ali, Hiltrud Stubbe, Rafael Lujan, Andrea Volterra
Circuit-Specific Control Of The Medial Entorhinal Inputs To The Dentate Gyrus By Atypical Presynaptic Nmdars Activated By Astrocytes, Iaroslav Savtchouk, Maria Amalia Di Castro, Rugina Ali, Hiltrud Stubbe, Rafael Lujan, Andrea Volterra
Biomedical Sciences Faculty Research and Publications
Here, we investigated the properties of presynaptic N-methyl-D-aspartate receptors (pre-NMDARs) at corticohippocampal excitatory connections between perforant path (PP) afferents and dentate granule cells (GCs), a circuit involved in memory encoding and centrally affected in Alzheimer’s disease and temporal lobe epilepsy. These receptors were previously reported to increase PP release probability in response to gliotransmitters released from astrocytes. Their activation occurred even under conditions of elevated Mg2+ and lack of action potential firing in the axons, although how this could be accomplished was unclear. We now report that these pre-NMDARs contain the GluN3a subunit conferring them low Mg2+ …
Regulation Of System Xc-By The Neuropeptide Pacap: Implications For Glutamate Transmission In Drug Addiction, Linghai Kong
Regulation Of System Xc-By The Neuropeptide Pacap: Implications For Glutamate Transmission In Drug Addiction, Linghai Kong
Dissertations (1934 -)
Drug addiction is a chronic brain disorder characterized by heightened relapse susceptibility. Drug-induced aberrant glutamate signaling in corticostriatal circuitry contributes to behaviors in virtually every preclinical model of drug seeking and correlates with drug craving in human. Here, we propose that glutamate signaling is a product of integrated activity between neurons and astrocytes, such that disruptions within astrocytes can stem from abnormal neuronal signaling (e.g., altered corticostriatal firing) and be the source of additional disruptions in other neuronal circuits. The astrocytic mechanism studied in these experiments is system xc- (Sxc) since drug-induced changes to this non-vesicular glutamate release mechanism contribute …
Pituitary Adenylate Cyclase-Activating Polypeptide Orchestrates Neuronal Regulation Of The Astrocytic Glutamate-Releasing Mechanism System XC−, Linghai Kong, Rebecca Albano, Aric Madayag, Nicholas Raddatz, John R. Mantsch, Sujean Choi, Doug Lobner, David A. Baker
Pituitary Adenylate Cyclase-Activating Polypeptide Orchestrates Neuronal Regulation Of The Astrocytic Glutamate-Releasing Mechanism System XC−, Linghai Kong, Rebecca Albano, Aric Madayag, Nicholas Raddatz, John R. Mantsch, Sujean Choi, Doug Lobner, David A. Baker
Biomedical Sciences Faculty Research and Publications
Glutamate signaling is achieved by an elaborate network involving neurons and astrocytes. Hence, it is critical to better understand how neurons and astrocytes interact to coordinate the cellular regulation of glutamate signaling. In these studies, we used rat cortical cell cultures to examine whether neurons or releasable neuronal factors were capable of regulating system xc-(Sxc), a glutamate-releasing mechanism that is expressed primarily by astrocytes and has been shown to regulate synaptic transmission. We found that astrocytes cultured with neurons or exposed to neuronal-conditioned media displayed significantly higher levels of Sxc activity. Next, we demonstrated that the pituitary …
Pacap And Cocaine Reinstatement: A Neuropeptide Expressed By Corticostriatal Neurons That Regulates Nucleus Accumbens Astrocytes, Linghai Kong, E. Hess, Brian Maunze, Matthew M. Hurley, Khadijah Makky, Sujean Choi, John R. Mantsch, David A. Baker
Pacap And Cocaine Reinstatement: A Neuropeptide Expressed By Corticostriatal Neurons That Regulates Nucleus Accumbens Astrocytes, Linghai Kong, E. Hess, Brian Maunze, Matthew M. Hurley, Khadijah Makky, Sujean Choi, John R. Mantsch, David A. Baker
Biomedical Sciences Faculty Research and Publications
Drug addiction involves heightened relapse vulnerability arising from persistent drug-induced neuro-adaptations, including a) hypofrontality which is thought to reflect reduced firing of cortical afferents to the nucleus accumbens (NAcc) and b) altered glutamate homeostasis in NAcc that likely involves reduced glutamate release and uptake by astrocytes. An important question is whether these forms of pathological plasticity are functionally linked such that reduced corticostriatal firing may result in aberrant regulation of astrocytes in the NAcc. To begin to evaluate this possibility, we first determined whether neurons regulate system xc- (Sxc) activity, a mechanism of non-vesicular glutamate release by astrocytes. We found …
Augmented Cystine–Glutamate Exchange By Pituitary Adenylate Cyclase-Activating Polypeptide Signaling Via The Vpac1 Receptor, Jon M. Resch, Rebecca Albano, Xiaoqian Liu, Julie Hjelmhaug, Doug Lobner, David A. Baker, Sujean Choi
Augmented Cystine–Glutamate Exchange By Pituitary Adenylate Cyclase-Activating Polypeptide Signaling Via The Vpac1 Receptor, Jon M. Resch, Rebecca Albano, Xiaoqian Liu, Julie Hjelmhaug, Doug Lobner, David A. Baker, Sujean Choi
Biomedical Sciences Faculty Research and Publications
In the central nervous system, cystine import in exchange for glutamate through system xc- is critical for the production of the antioxidant glutathione by astrocytes, as well as the maintenance of extracellular glutamate. Therefore, regulation of system xc- activity affects multiple aspects of cellular physiology and may contribute to disease states. Pituitary adenylate cyclase-activating polypeptide (PACAP) is a neuronally derived peptide that has already been demonstrated to modulate multiple aspects of glutamate signaling suggesting PACAP may also target activity of cystine–glutamate exchange via system xc-. In this study, 24-h treatment of primary cortical …