title: GABA and Endocannabinoids Mediate Depotentiation of Schaffer Collateral Synapses Induced by Stimulation of Temperoammonic Inputs.
abstract: Long-term potentiation (LTP) of Schaffer collateral (SC) synapses in the hippocampus is thought to play a key role in episodic memory formation. Because the hippocampus is a shorter-term, limited capacity storage system, repeated bouts of learning and synaptic plasticity require that SC synapses reset to baseline at some point following LTP. We previously showed that repeated low frequency activation of temperoammonic (TA) inputs to the CA1 region depotentiates SC LTP without persistently altering basal transmission. This heterosynaptic depotentiation involves adenosine A1 receptors but not N-methyl-D-aspartate receptors, metabotropic glutamate receptors or L-type calcium channels. In the present study, we used rat hippocampal slices to explore other messengers contributing to TA-induced SC depotentiation, and provide evidence for the involvement of cannabinoid-1 and γ-aminobutyric acid (GABA) type-A receptors as more proximal signaling events leading to synaptic resetting, with A1 receptor activation serving as a downstream event. Surprisingly, we found that TA-induced SC depotentiation is independent of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA)/kainate glutamate receptors. We also examined the involvement of mitogen-activated protein kinases (MAPKs), and found a role for extracellular-signal related kinase 1/2 and p38 MAPK, but not c-Jun-N-terminal kinase. These results indicate that low frequency stimulation of TA inputs to CA1 activates a complex signaling network that instructs SC synaptic resetting. The involvement of GABA and endocannabinoids suggest mechanisms that could contribute to cognitive dysfunction associated with substance abuse and neuropsychiatric disorders.
authors: Department of Psychiatry, Washington University School of Medicine, St. Louis, MO, United States of America.|Taylor Family Institute for Innovative Psychiatric Research, Washington University School of Medicine, St. Louis, MO, United States of America.|Washington University Center for Brain Research in Mood Disorders, Washington University School of Medicine, St. Louis, MO, United States of America.
authors: Yukitoshi
authors: Y
authors: Izumi
authors: Department of Psychiatry, Washington University School of Medicine, St. Louis, MO, United States of America.|Taylor Family Institute for Innovative Psychiatric Research, Washington University School of Medicine, St. Louis, MO, United States of America.|Washington University Center for Brain Research in Mood Disorders, Washington University School of Medicine, St. Louis, MO, United States of America.
authors: Charles F
authors: CF
authors: Zorumski
mesh_terms: D000818:Animals; D001921:Brain / Q000473:pathology / Q000502:physiology; D056547:CA1 Region, Hippocampal / Q000502:physiology; D020746:Calcium Channels, L-Type / Q000378:metabolism / Q000502:physiology; D003072:Cognition Disorders / Q000503:physiopathology; D063388:Endocannabinoids / Q000737:chemistry / Q000378:metabolism / Q000502:physiology*; D006624:Hippocampus / Q000378:metabolism / Q000473:pathology; D017774:Long-Term Potentiation; D036881:Long-Term Synaptic Depression; D020935:MAP Kinase Signaling System; D051381:Rats; D018091:Receptors, AMPA / Q000378:metabolism / Q000502:physiology; D017470:Receptors, Glutamate / Q000378:metabolism / Q000502:physiology; D018092:Kainic Acid Receptors / Q000378:metabolism / Q000502:physiology; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism / Q000502:physiology; D015398:Signal Transduction; D019966:Substance-Related Disorders / Q000503:physiopathology; D013569:Synapses / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D005680:gamma-Aminobutyric Acid / Q000737:chemistry / Q000502:physiology*; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism / Q000502:physiology
chemical_list: D020746:Calcium Channels, L-Type; D063388:Endocannabinoids; D018091:Receptors, AMPA; D017470:Receptors, Glutamate; D018092:Kainic Acid Receptors; D016194:Receptors, N-Methyl-D-Aspartate; D005680:gamma-Aminobutyric Acid; D048051:p38 Mitogen-Activated Protein Kinases