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The microtubule-associated protein tau accumulates in Alzheimer's and other fatal dementias, which manifest when forebrain neurons die. Recent advances in understanding these disorders indicate that brain dysfunction precedes neurodegeneration, but the role of tau is unclear. Here, we show that early tau-related deficits develop not from the loss of(More)
We investigated mitogen-activated protein kinase (MAPK) modulation of dendritic, A-type K+ channels in CA1 pyramidal neurons in the hippocampus. Activation of cAMP-dependent protein kinase A (PKA) and protein kinase C (PKC) leads to an increase in the amplitude of backpropagating action potentials in distal dendrites through downregulation of transient K+(More)
Shal-type (Kv4.x) K(+) channels are expressed in a variety of tissue, with particularly high levels in the brain and heart. These channels are the primary subunits that contribute to transient, voltage-dependent K(+) currents in the nervous system (A currents) and the heart (transient outward current). Recent studies have revealed an enormous degree of(More)
The dendrites of CA1 pyramidal neurons in the hippocampus express numerous types of voltage-gated ion channel, but the distributions or densities of many of these channels are very non-uniform. Sodium channels in the dendrites are responsible for action potential (AP) propagation from the axon into the dendrites (back-propagation); calcium channels are(More)
Calcium-calmodulin-dependent kinase II (CaMKII) has a long history of involvement in synaptic plasticity, yet little focus has been given to potassium channels as CaMKII targets despite their importance in repolarizing EPSPs and action potentials and regulating neuronal membrane excitability. We now show that Kv4.2 acts as a substrate for CaMKII in vitro(More)
Isoprenoids and prenylated proteins have been implicated in the pathophysiology of Alzheimer disease (AD), including amyloid-β precursor protein metabolism, Tau phosphorylation, synaptic plasticity, and neuroinflammation. However, little is known about the relative importance of the two protein prenyltransferases, farnesyltransferase (FT) and(More)
Complex computations in the nervous system begin with electrical signals generated in single neurons. Such signals include action potentials mediated by the opening of voltage-dependent ion channels, and synaptic potentials arising from neurotransmitter receptor activation. The amplitude, waveform, and propagation of action potentials and synaptic(More)
Voltage-dependent (Kv)4.2-encoded A-type K+ channels play an important role in controlling neuronal excitability and are subject to modulation by various protein kinases, including ERK. In studies of ERK modulation, the organic compound U0126 is often used to suppress the activity of MEK, which is a kinase immediately upstream from ERK. We have observed(More)
Kv4.2-mediated A-type K(+) channels in dendrites act to dampen back-propagating action potentials, constrain coincidence detection, and modify synaptic properties. Because of naturally high concentrations in the hippocampus, genetic deletion of this protein results in enhanced CA1 dendritic excitability and a broader signal integration time window with(More)
Active conductances located and operating on neuronal dendrites are expected to regulate synaptic integration and plasticity. We investigate how Kv4.2-mediated A-type K(+) channels and Ca(2+) -activated K(+) channels are involved in the induction process of Hebbian-type plasticity that requires correlated pre- and postsynaptic activities. In CA1 pyramidal(More)