“At many synapses, a period of high-frequency (tetanic) stimulation can evoke a transient increase in synaptic strength known as posttetanic potentiation (PTP) (Feng, 1941, Griffith, 1990, Magleby, 1987, Magleby and Zengel, 1975, Zucker and Lara-Estrella, 1983 and Zucker and Regehr, 2002). PTP is thought to provide an important means of synaptic regulation that can contribute
to working memory and information processing (Abbott and Regehr, 2004 and Silva et al., 1996). LY2157299 concentration Many high-frequency stimuli are needed to induce PTP, and the frequency and duration of tetanic stimulation regulate the magnitude and duration of the enhancement (which lasts tens of seconds to minutes) (Habets and Borst, 2005, Habets and Borst, 2007, Korogod
et al., 2005, Lev-Tov and Rahamimoff, 1980, Magleby, 1979 and Zucker, 1989). Tetanic stimulation also increases both the frequency and the magnitude of spontaneous miniature excitatory postsynaptic currents (mEPSCs) at many (Castillo and Katz, 1954, Delaney and Tank, 1994, Eliot et al., 1994, Habets and Borst, 2005, He et al., 2009, Korogod et al., 2005, Korogod et al., 2007 and Magleby, 1987), but not all (Brager et al., 2003) synapses. It is not known whether increases in the frequency and amplitude of spontaneous transmission and the increase in evoked release share a common presynaptic mechanism. Numerous mechanisms could contribute to PTP. According to the leading hypothesis, known as the residual calcium hypothesis, tetanic stimulation leads to an accumulation
of calcium in the presynaptic terminal, and an accompanying increase in the probability of release Carfilzomib mw that persists for tens of seconds (Brager et al., 2003, Delaney and Tank, 1994, Delaney et al., 1989, Regehr et al., 1994 and Zucker and Regehr, 2002). Other possibilities include an increase in the size of the readily releasable pool mafosfamide of vesicles (Habets and Borst, 2005 and Lee et al., 2008), an increase in the size of mEPSCs as a result of vesicles fusing with each other before ultimately fusing with the plasma membrane (He et al., 2009), a change in action potential waveform (Eccles and Krnjevic, 1959 and Habets and Borst, 2005) and an increase in calcium entry (Habets and Borst, 2005 and Habets and Borst, 2006). Pharmacological studies have implicated protein kinase C (PKC) in PTP. Phorbol esters, activators of PKC (Newton, 2001), increase the amplitude of evoked release and occlude PTP (Hori et al., 1999, Korogod et al., 2007, Lou et al., 2005, Lou et al., 2008, Malenka et al., 1986, Oleskevich and Walmsley, 2000, Rhee et al., 2002, Shapira et al., 1987, Virmani et al., 2005 and Wierda et al., 2007). Phorbol esters also increase the frequency of mEPSCs (Hori et al., 1999, Lou et al., 2005, Lou et al., 2008, Oleskevich and Walmsley, 2000 and Parfitt and Madison, 1993). In addition, PKC inhibitors reduce the magnitude of PTP at many synapses (Alle et al., 2001, Beierlein et al., 2007, Brager et al.