Neuregulin and Dopamine D4 Receptors Contribute Independently to Depotentiation of Schaffer Collateral LTP by Temperoammonic Path Stimulation.
Prior studies have found that dopamine (DA), acting at D4 receptors, and neuregulin (NRG), likely acting at ErbB4 receptors, are involved in a form of depotentiation of long-term potentiation (LTP) at Schaffer collateral (SC) synapses in the hippocampus. Furthermore, DA and NRG actions are intertwined in that NRG induces DA release. We previously found that low-frequency stimulation (LFS) of temperoammonic (TA) inputs to area CA1 also depotentiates previously established SC LTP through a complex signaling pathway involving endocannabinoids, GABA, adenosine, and mitogen-activated protein kinases (MAPKs), but not glutamate. In the present studies, we found that TA-induced SC depotentiation in hippocampal slices from Sprague-Dawley albino rats also involves activation of both D4 receptors and NRG-activated ErbB receptors, but that the roles of these two modulator systems are independent with D4 receptor antagonism failing to alter chemical depotentiation by NRG1β. Furthermore, a selective D4 receptor agonist was unable to depotentiate SC LTP when administered alone, suggesting that D4 receptor activation is necessary but not sufficient for TA-induced SC depotentiation. Chemical depotentiation by NRG1β was inhibited by a Pan-ErbB antagonist and by picrotoxin (PTX), an antagonist of GABA-A receptors (GABAARs), indicating that NRG likely promotes SC depotentiation via effects on GABA and interneurons. These findings have implications for understanding the role of DA and NRG in cognitive dysfunction associated with neuropsychiatric illnesses.
['Izumi|Yukitoshi|Y|0000-0002-5596-1031', 'Zorumski|Charles F|CF|']
D000818:Animals D000831:Animals, Newborn D001703:Biophysics D003517:Cyclopentanes D018492:Dopamine Antagonists D004305:Dose-Response Relationship, Drug D004558:Electric Stimulation D018756:GABA Antagonists D006624:Hippocampus D066298:In Vitro Techniques D017774:Long-Term Potentiation D036881:Long-Term Synaptic Depression D009415:Nerve Net D020890:Neuregulin-1 D020880:Neuregulins D010852:Picrotoxin D011743:Pyrimidines D051381:Rats D017207:Rats, Sprague-Dawley D050638:Receptors, Dopamine D4
hippocampus endocannabinoids GABA adenosine ErbB perforant path