Dopamine D1/5 receptor-mediated long-term potentiation of intrinsic excitability in rat prefrontal cortical neurons: Ca2+-dependent intracellular signaling

作者：Chen Long; Bohanick Joseph D; Nishihara Makoto; Seamans Jeremy K; Yang Charles R^*

来源：Journal of Neurophysiology, 2007, 97(3): 2448-2464.

DOI：10.1152/jn.00317.2006

Prefrontal cortex (PFC) dopamine D1/5 receptors modulate long- and short-term neuronal plasticity that may contribute to cognitive functions. Synergistic to synaptic strength modulation, direct postsynaptic D1/5 receptor activation also modulates voltage-dependent ionic currents that regulate spike firing, thus altering the neuronal input-output relationships in a process called long- term potentiation of intrinsic excitability (LTP-IE). Here, the intracellular signals that mediate this D1/5 receptor-dependent LTP-IE were determined using whole cell current-clamp recordings in layer V/VI rat pyramidal neurons from PFC slices. After blockade of all major amino acid receptors (V-hold = -65 mV) brief tetanic stimulation ( 20 Hz) of local afferents or application of the D1 agonist SKF81297 (0.2-50 mu M) induced LTP-IE, as shown by a prolonged (> 40 min) increase in depolarizing pulse-evoked spike firing. Pretreatment with the D1/5 antagonist SCH23390 ( 1 mu M) blocked both the tetani- and D1/5 agonist-induced LTP-IE, suggesting a D1/5 receptor-mediated mechanism. The SKF81297-induced LTP-IE was significantly attenuated by Cd2+, [Ca2+](i) chelation, by inhibition of phospholipase C, protein kinase-C, and Ca2+/calmodulin kinase-II, but not by inhibition of adenylate cyclase, protein kinase-A, MAP kinase, or L-type Ca2+ channels. Thus this form of D1/5 receptor-mediated LTP-IE relied on Ca2+ influx via non-L-type Ca2+ channels, activation of PLC, intracellular Ca2+ elevation, activation of Ca2+-dependent CaMKII, and PKC to mediate modulation of voltage-dependent ion channel(s). This D1/5 receptor-mediated modulation by PKC coexists with the previously described PKA-dependent modulation of K+ and Ca2+ currents to dynamically regulate overall excitability of PFC neurons.

• 出版日期2007-3
• 单位南京中医药大学