Different Mechanisms May Be Required For Maintenance Of Nimda Receptor-dependent And Independent Forms Of Long-term Potentiation
activation; area; ca1; calcium; calcium channels; calmodulin inhibitors; d-aspartate receptors; dentate gyrus; depression; glutamate; hippocampal slice; induction; Neurosciences & Neurology; protein kinase; protein-kinase-c; rat hippocampal slices
In hippocampal area CA1, long-term potentiation (LTP) is induced by tetanic stimulation protocols that activate N-methyl-D-aspartate (NMDA) receptors. In addition, some stimulation protocols can induce LTP during NMDA receptor blockade. An initial signal in both NMDA receptor-dependent and independent LTPs is increased intracellular Ca2+ concentration in postsynaptic neurons. It therefore seems possible that subsequent steps leading to expression and maintenance of potentiation are shared whether or not LTP is induced through NMDA receptor activation. We tested this hypothesis by applying a broad spectrum protein kinase inhibitor, previously shown to inhibit NMDA receptor-dependent LTP. In agreement with earlier reports, we found that H-7 inhibited NMDA receptor-dependent LTP when applied either during tetanic stimulation, or beginning 30 min following tetanic stimulation. In contrast, NMDA receptor-independent LTP was not inhibited by H-7 applied during or following tetanic stimulation. We also tested for mutual occlusion between NMDA receptor-dependent and independent LTPs. Although induction of NMDA receptor-independent LTP did not occlude later induction of NMDA receptor-dependent LTP, induction of NMDA receptor-dependent LTP did occlude NMDA receptor-independent LTP. While the kinase inhibitor experiment showed a clear difference between NMDA receptor-dependent and independent LTPs, the occlusion experiments suggest an interaction between the signalling pathways for the two LTPs. (C) 1995 Wiley-Liss, Inc.
Grover L M; Teyler T J
Synapse
1995
1995-02
Journal Article or Conference Abstract Publication
<a href="http://doi.org/10.1002/syn.890190208" target="_blank" rel="noreferrer noopener">10.1002/syn.890190208</a>
Knockdown of amyloid precursor protein normalizes cholinergic function in a cell line derived from the cerebral cortex of a trisomy 16 mouse: An animal model of Down syndrome
16 mice; abnormalities; acetylcholine; acetylcholine-release; alzheimers-disease; amyloid; antisense; beta-protein; calcium; cell line; Down syndrome; Neurosciences & Neurology; neurotoxicity; peptide; rat hippocampal slices; root ganglion neurons
We have generated immortal neuronal cell lines from normal and trisomy 16 (Ts16) mice, a model for Down syndrome (DS). Ts16 lines overexpress DS-related genes (App, amyloid precursor protein; Sod1, Cu/Zn superoxide dismutase) and show altered cholinergic function (reduced choline uptake, ChAT expression and fractional choline release after stimulation). As previous evidence has related amyloid to cholinergic dysfunction, we reduced APP expression using specific mRNA antisense sequences in our neuronal cell line named CTb, derived from Ts16 cerebral cortex, compared to a cell line derived from a normal animal, named CNh. After transfection, Western blot studies showed APP expression knockdown in CTb cells of 36% (24 hr), 40.4% (48 hr), and 50.2% (72 hr) compared to CNh. Under these reduced APP levels, we studied 3 H-choline uptake in CTb and CNh cells. CTb, as reported previously, expressed reduced choline uptake compared to CNh cells (75%, 90%, and 69% reduction at 1, 2, and 5 min incubation, respectively). At 72 hr of APP knockdown, choline uptake levels were essentially similar in both cell types. Further, fractional release of H-3-choline in response to glutamate, nicotine, and depolarization with KCI showed a progressive increase after APP knockdown, reaching values similar to those of CNh after 72 hr of transfection. The results suggest that APP overexpression in CTb cells contributes to impaired cholinergic function, and that gene knockdown in CTb cells is a relevant tool to study DS-related dysfunction. (c) 2006 Wiley-Liss, Inc.
Opazo P; Saud K; de Saint Pierre M; Cardenas A M; Allen D D; Segura-Aguilar J; Caviedes R; Caviedes P
Journal of Neuroscience Research
2006
2006-11
Journal Article
<a href="http://doi.org/10.1002/jnr.21035" target="_blank" rel="noreferrer noopener">10.1002/jnr.21035</a>