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Association of PKA with the AMPA receptor GluR1 subunit via the A kinase anchor protein AKAP150 is crucial for GluR1 phosphorylation. Mutating the AKAP150 gene to specifically prevent PKA binding reduced PKA within postsynaptic densities (>70%). It abolished hippocampal LTP in 7-12 but not 4-week-old mice. Inhibitors of PKA and of GluR2-lacking AMPA receptors blocked single tetanus LTP in hippocampal slices of 8 but not 4-week-old WT mice. Inhibitors of GluR2-lacking AMPA receptors also prevented LTP in 2 but not 3-week-old mice. Other studies demonstrate that GluR1 homomeric AMPA receptors are the main GluR2-lacking AMPA receptors in adult hippocampus and require PKA for their functional postsynaptic expression during potentiation. AKAP150-anchored PKA might thus critically contribute to LTP in adult hippocampus in part by phosphorylating GluR1 to foster postsynaptic accumulation of homomeric GluR1 AMPA receptors during initial LTP in 8-week-old mice.
Pubmed ID: 17972919 RIS Download
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NEURON is a simulation environment for modeling individual neurons and networks of neurons. It provides tools for conveniently building, managing, and using models in a way that is numerically sound and computationally efficient. It is particularly well-suited to problems that are closely linked to experimental data, especially those that involve cells with complex anatomical and biophysical properties. NEURON has benefited from judicious revision and selective enhancement, guided by feedback from the growing number of neuroscientists who have used it to incorporate empirically-based modeling into their research strategies. NEURON's computational engine employs special algorithms that achieve high efficiency by exploiting the structure of the equations that describe neuronal properties. It has functions that are tailored for conveniently controlling simulations, and presenting the results of real neurophysiological problems graphically in ways that are quickly and intuitively grasped. Instead of forcing users to reformulate their conceptual models to fit the requirements of a general purpose simulator, NEURON is designed to let them deal directly with familiar neuroscience concepts. Consequently, users can think in terms of the biophysical properties of membrane and cytoplasm, the branched architecture of neurons, and the effects of synaptic communication between cells. * helps users focus on important biological issues rather than purely computational concerns * has a convenient user interface * has a user-extendable library of biophysical mechanisms * has many enhancements for efficient network modeling * offers customizable initialization and simulation flow control * is widely used in neuroscience research by experimentalists and theoreticians * is well-documented and actively supported * is free, open source, and runs on (almost) everything
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