Browsing by Author "Deng, Ping"

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    Depression of fast excitatory synaptic transmission in large aspiny neurons of the neostriatum after transient forebrain ischemia
    (Society for Neuroscience, 2002-12) Pang, Zhi-Ping; Deng, Ping; Ruan, Yi-Wen; Xu, Zao C.; Anatomy and Cell Biology, School of Medicine
    Spiny neurons in the neostriatum die within 24 hr after transient global ischemia, whereas large aspiny (LA) neurons remain intact. To reveal the mechanisms of such selective cell death after ischemia, excitatory neurotransmission was studied in LA neurons before and after ischemia. The intrastriatally evoked fast EPSCs in LA neurons were depressed < or =24 hr after ischemia. The concentration-response curves generated by application of exogenous glutamate in these neurons were approximately the same before and after ischemia. A train of five stimuli (100 Hz) induced progressively smaller EPSCs, but the proportion of decrease in EPSC amplitude at 4 hr after ischemia was significantly smaller compared with control and at 24 hr after ischemia. Parallel depression of NMDA receptor and AMPA receptor-mediated EPSCs was also observed after ischemia, supporting the involvement of presynaptic mechanisms. The adenosine A1 receptor antagonist 8-cyclopentyl-1,3-dipropylxanthine blocked the inhibition of evoked EPSCs at 4 hr after ischemia but not at 24 hr after ischemia. Electron microscopic studies demonstrated that the most presynaptic terminals in the striatum had a normal appearance at 4 hr after ischemia but showed degenerating signs at 24 hr after ischemia. These results indicated that the excitatory neurotransmission in LA neurons was depressed after ischemia via presynaptic mechanisms. The depression of EPSCs shortly after ischemia might be attributable to the enhanced adenosine A1 receptor function on synaptic transmission, and the depression at late time points might result from the degeneration of presynaptic terminals.
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    Involvement of I(h) in dopamine modulation of tonic firing in striatal cholinergic interneurons
    (Society for Neuroscience, 2007-03-21) Deng, Ping; Zhang, Yuchun; Xu, Zao C.; Anatomy and Cell Biology, School of Medicine
    Striatal cholinergic interneurons are tonically active neurons and respond to sensory stimuli by transiently suppressing firing that is associated with sensorimotor learning. The pause in tonic firing is dependent on dopaminergic activity; however, its cellular mechanisms remain unclear. Here, we report evidence that dopaminergic inhibition of hyperpolarization-activated cation current (I(h)) is involved in this process. In neurons exhibiting regular firing in vitro, exogenous application of dopamine caused a prolongation of the depolarization-induced pause and an increase in the duration of slow afterhyperpolarization (sAHP) after depolarization. Partially blocking I(h) with specific blocker ZD7288 (4-ethylphenylamino-1,2-dimethyl-6-methylaminopyrimidinium chloride) reduced firing and mimicked the effects of dopamine on sAHP. The I(h), being active at membrane potentials negative than -50 mV, was inhibited by dopamine via activation of the D2-like receptor, but not D1-like receptor. The inhibitory effects of the D2 receptor activation on I(h) were mediated through a protein kinase A-independent cyclic AMP pathway. Consistently, D2-like receptor agonist quinpirole showed comparable effects on sAHP and firing rate as those induced by I(h) channel blocker. Moreover, dopamine was unable to further affect the sAHP duration in neurons when I(h) was blocked. These findings indicate that D2 receptor-dependent inhibition of I(h) may be a novel mechanism for modulating the pause response in tonic firing in cholinergic interneurons.