@misc{oai:ir.soken.ac.jp:00001138, author = {山下, 哲司 and ヤマシタ, テツジ and YAMASHITA, Tetsuji}, month = {2016-02-17, 2016-02-17}, note = {Mesencephalic dopamine (DA) neurons receive a keen interest of many researchers because of their physiological and patho-physiological importance. Especially, the mechanism to modulate their firing pattern has been investigated for many years but still remains elusive. DA neurons are supposed to be modulated by excitatory and inhibitory inputs from other parts of the brain. It has been shown that N-metyl-Daspartate receptors (NMDARs) play an important role in switching the firing pattern from tonic to burst firing mode, but it has been also claimed that the activation of NMDARs dose not explain the whole mechanism of the induction of bursting activity. On the other hand, cholinergic afferent projection from the pedunculopontine nucleus has recently been highlighted because both nicotinic and muscarinic acetylcholine receptors were reported to function in DA neurons. In this article, we will show that Ca2+ influx through nicotinic acetylcholine receptors in DA neurons subsequently activate inward current which is sensitive to fulfenamic acid (FFA) and phenytoin and this current is presumed to be a subtype of calcium-activated nonselective cation current, ICAN. This channel exhibits a negative slope conductance and induces a dramatic change in firing pattern of DA neurons from tonic single spikes to a multiple bursting spikes by markedly enhancing their depolarizing responses. Furthermore, the activation of this channel depends not only on intracellular Ca2+ but also on the calmodulin-Ca2+/calmodulin dependent protein kinase II pathway. In addition, we found that the activation of the FFA- and phenytoin-sensitive current plays a major role in enhancement of the synaptic response to glutamatergic inputs when they are coincident with the cholinergic inputs. Taken together, our results strongly suggest that cholinergic inputs to DA neurons modulate the firing pattern of DA neurons by the activation of ICAN induced by Ca2+ influx through the nicotinic receptors., application/pdf, 総研大甲第727号}, title = {Calcium-dependent inward current induced by nicotinic acetylcholine receptors in mesencephalic dopamine neurons}, year = {} }