Calcium-independent afterdepolarization regulated by serotonin in anterior thalamus.
Previous studies have identified an afterdepolarization (ADP) in thalamocortical neurons that is mediated by an upregulation of the hyperpolarization-activated current I(h). This ADP has been suggested to play a key role in the generation of spindle oscillations. In the lateral geniculate nucleus, upregulation of I(h) has been shown to be signaled by a rise in intracellular calcium leading to the activation of adenylate cyclase and formation of cAMP. However, it is unclear how generalizable this mechanism is to other thalamic nuclei. We have used whole cell recording to examine the electrophysiological properties of neurons of the anterodorsal thalamic nucleus, a nucleus thought not to undergo spindle oscillations. We now report that cells in this nucleus also display an ADP mediated by I(h). Surprisingly, the ADP and the underlying upregulation of I(h) persisted even after buffering intracellular calcium and blocking calcium influx. These results indicate that, in neurons of the anterodorsal thalamic nucleus, an I(h)-mediated ADP can occur through a mechanism that does not involve a rise in intracellular calcium. We next examined the possibility that this calcium-independent ADP might be modulated by serotonin. Serotonin produced a robust enhancement in the amplitude of the ADP even after strong buffering of intracellular calcium and blockade of calcium channels. These results indicate that neurons of the anterodorsal thalamic nucleus display a calcium-independent, I(h)-mediated ADP and that this ADP is a target for regulation by serotonin. These findings identify a novel mechanism by which serotonin can regulate neuronal excitability.
Chapin
E M
EM
Department of Psychiatry and Behavioral Neurosciences and Cellular and Clinical Neurobiology Training Program, Wayne State University School of Medicine, Detroit, Michigan 48201, USA.
Andrade
R
R
D000818:Animals; D020643:Anterior Thalamic Nuclei / Q000166:cytology / Q000378:metabolism*; D002104:Cadmium / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism*; D004533:Egtazic Acid / Q000031:analogs & derivatives / Q000494:pharmacology; D004558:Electric Stimulation; D066298:In Vitro Techniques; D007424:Intracellular Fluid / Q000187:drug effects / Q000378:metabolism; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D009532:Nickel / Q000494:pharmacology; D018408:Patch-Clamp Techniques; D011743:Pyrimidines / Q000494:pharmacology; D012701:Serotonin / Q000378:metabolism* / Q000494:pharmacology; D015854:Up-Regulation
D011743:Pyrimidines; D002104:Cadmium; C082246:ICI D2788; D012701:Serotonin; D004533:Egtazic Acid; D009532:Nickel; C025603:1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid; D002118:Calcium