The T-type voltage-gated calcium channel as a molecular target of the novel cognitive enhancer ST101: enhancement of long-term potentiation and CaMKII autophosphorylation in rat cortical slices

The synaptic phenomena of long-term potentiation (LTP) and long-term depression (LTD) have been intensively studied for over twenty-five years. Although many diverse aspects of these forms of plasticity have been observed, no single theory has offered a unifying explanation for them. Here, a statistical “bin” model is proposed to account for a variety of features observed in LTP and LTD experiments performed with field potentials in mammalian cortical slices. It is hypothesized that long-term synaptic changes will be induced when statistically unlikely conjunctions of pre- and postsynaptic activity occur. This hypothesis implies that finite changes in synaptic strength will be proportional to information transmitted by conjunctions and that excitatory synapses will obey a Hebbian rule (Hebb, 1949). Using only one set of constants, the bin model offers an explanation as to why synaptic strength decreases in a decelerating manner during LTD induction (Mulkey & Malenka, 1992); why the induction protocols for LTP and LTD are asymmetric (Dudek & Bear, 1992; Mulkey & Malenka, 1992); why stimulation over a range of frequencies produces a frequency-response curve similar to that proposed by the BCM theory (Bienenstock, Cooper, & Munro, 1982; Dudek & Bear, 1992); and why this curve would shift as postsynaptic activity is changed (Kirkwood, Rioult, & Bear, 1996). In addition, the bin model offers an alternative to the BCM theory by predicting that changes in postsynaptic activity will produce vertical shifts in the curve rather than merely horizontal shifts.

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Changes in the paired-pulse ratio after long-term potentiation induced by 2- and 100-Hz tetanus in rat visual cortical slices

Brain Research ◽

10.1016/j.brainres.2004.06.046 ◽

2004 ◽

Vol 1021 (1) ◽

pp. 146-150 ◽

Cited By ~ 4

Author(s):

Bin Pan ◽

Dong-Wei Yang ◽

Tai-Zhen Han ◽

Wen Xie

Keyword(s):

Long Term Potentiation ◽

Paired Pulse ◽

Pulse Ratio ◽

Term Potentiation ◽

Visual Cortical ◽

Cortical Slices

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Enhancement of long-term potentiation by the calcium channel agonist Bayer K8644 in CA1 of the rat hippocampus in vitro

Neuroscience Letters ◽

10.1016/0304-3940(87)90481-2 ◽

1987 ◽

Vol 80 (3) ◽

pp. 351-355 ◽

Cited By ~ 39

Author(s):

Declan Mulkeen ◽

Roger Anwyl ◽

Michael J. Rowan

Keyword(s):

Calcium Channel ◽

Long Term Potentiation ◽

Rat Hippocampus ◽

Term Potentiation ◽

Channel Agonist

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Aging Differentially Alters Forms of Long-Term Potentiation in Rat Hippocampal Area CA1

Journal of Neurophysiology ◽

10.1152/jn.1998.79.1.334 ◽

1998 ◽

Vol 79 (1) ◽

pp. 334-341 ◽

Cited By ~ 133

Author(s):

Subbakrishna Shankar ◽

Timothy J. Teyler ◽

Norman Robbins

Keyword(s):

Calcium Channel ◽

Hippocampal Slices ◽

Long Term Potentiation ◽

Voltage Dependent Calcium Channel ◽

Area Ca1 ◽

Age Related ◽

Term Potentiation ◽

Voltage Dependent ◽

Hippocampal Area

Shankar, Subbakrishna, Timothy J. Teyler, and Norman Robbins. Aging differentially alters forms of long-term potentiation in rat hippocampal area CA1. J. Neurophysiol. 79: 334–341, 1998. Long-term potentiation (LTP) of the Schaffer collateral/commissural inputs to CA1 in the hippocampus was shown to consist of N-methyl-d-aspartate receptor (NMDAR) and voltage-dependent calcium channel (VDCC) dependent forms. In this study, the relative contributions of these two forms of LTP in in vitro hippocampal slices from young (2 mo) and old (24 mo) Fischer 344 rats were examined. Excitatory postsynaptic potentials (EPSP) were recorded extracellularly from stratum radiatum before and after a tetanic stimulus consisting of four 200-Hz, 0.5-s trains given 5 s apart. Under control conditions, a compound LTP consisting of both forms was induced and was similar, in both time course and magnitude, in young and old animals. NMDAR-dependent LTP (nmdaLTP), isolated by the application of 10 μM nifedipine (a voltage-dependent calcium channel blocker), was significantly reduced in magnitude in aged animals. The VDCC dependent form (vdccLTP), isolated by the application of 50 μM d,l-2-amino-5-phosphonvalerate (APV), was significantly larger in aged animals. Although both LTP forms reached stable values 40–60 min posttetanus in young animals, in aged animals vdccLTP increased and nmdaLTP decreased during this time. In both young and old animals, the sum of the two isolated LTP forms approximated the magnitude of the compound LTP, and application of APV and nifedipine or genestein (a tyrosine kinase inhibitor) together blocked potentiation. These results suggest that aging causes a shift in synaptic plasticity from NMDAR-dependent mechanisms to VDCC-dependent mechanisms. The data are consistent with previous findings of increased L-type calcium current and decreased NMDAR number in aged CA1 cells and may help explain age-related deficits in learning and memory.

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