Alpha2-adrenergic receptors modify dendritic spike generation via HCN channels in the prefrontal cortex.
Although dendritic spikes are generally thought to be restricted to the distal apical dendrite, we know very little about the possible modulatory mechanisms that set the spatial limits of dendritic spikes. Our experiments demonstrated that high-frequency trains of backpropagating action potentials avoided filtering in the apical dendrite and initiated all-or-none dendritic Ca(2+) transients associated with dendritic spikes in layer 5 pyramidal neurons of the prefrontal cortex. The block of hyperpolarization-activated currents (I(h)) by ZD7288 could shift the frequency threshold and decreased the number of action potentials required to produce the all-or-none Ca(2+) transient. Activation of alpha(2)-adrenergic receptors could also shift the frequency domain of spike induction to lower frequencies. Our data suggest that noradrenergic activity in the prefrontal cortex influences dendritic I(h) and extends the zone of dendritic spikes in the apical dendrite via alpha(2)-adrenergic receptors. This mechanism might be one cellular correlate of the alpha(2)-receptor-mediated actions on working memory.
Barth
Albert M I
AM
Institute of Experimental Medicine, Hungarian Academy of Sciences, Budapest, Hungary.
Vizi
E Sylvester
ES
Zelles
Tibor
T
Lendvai
Balazs
B
D000200:Action Potentials / Q000187:drug effects / Q000502:physiology*; D000316:Adrenergic alpha-Agonists / Q000494:pharmacology; D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D000818:Animals; D020013:Calcium Signaling / Q000187:drug effects / Q000502:physiology; D002316:Cardiotonic Agents / Q000494:pharmacology; D054815:Cyclic Nucleotide-Gated Cation Channels / Q000187:drug effects / Q000378:metabolism*; D003712:Dendrites / Q000187:drug effects / Q000378:metabolism*; D064428:Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels; D008297:Male; D009415:Nerve Net / Q000187:drug effects / Q000378:metabolism; D009434:Neural Pathways / Q000187:drug effects / Q000378:metabolism; D009638:Norepinephrine / Q000378:metabolism; D009924:Organ Culture Techniques; D018408:Patch-Clamp Techniques; D015221:Potassium Channels / Q000187:drug effects / Q000378:metabolism*; D017397:Prefrontal Cortex / Q000187:drug effects / Q000378:metabolism*; D017966:Pyramidal Cells / Q000187:drug effects / Q000378:metabolism; D011743:Pyrimidines / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D018341:Receptors, Adrenergic, alpha-2 / Q000187:drug effects / Q000378:metabolism*; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology
D000316:Adrenergic alpha-Agonists; D000317:Adrenergic alpha-Antagonists; D002316:Cardiotonic Agents; D054815:Cyclic Nucleotide-Gated Cation Channels; D064428:Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels; D015221:Potassium Channels; D011743:Pyrimidines; D018341:Receptors, Adrenergic, alpha-2; C082246:ICI D2788; D009638:Norepinephrine