Thu, 21 Aug 2008 14:16:03 BST CiteULike: starz1010101's h-current http://www.citeulike.org/user/starz1010101/tag/h-current CiteULike.org en-gb Copyright © 2004-2008 citeulike.org http://www.citeulike.org/user/starz1010101/article/2210712 <i>J. Neurosci., Vol. 27, No. 51. (19 December 2007), pp. 13926-13937.</i><br /><br />Bidirectional changes in synaptic strength are the proposed cellular correlate for information storage in the brain. Plasticity of intrinsic excitability, however, may also be critical for regulating the firing of neurons during mnemonic tasks. We demonstrated previously that the induction long-term potentiation was accompanied by a persistent decrease in CA1 pyramidal neuron excitability (Fan et al., 2005). We show here that induction of long-term depression (LTD) by 3 Hz pairing of back-propagating action potentials with Schaffer collateral EPSPs was accompanied by an overall increase in CA1 neuronal excitability. This increase was observed as an increase in the number of action potentials elicited by somatic current injection and was caused by an increase in neuronal input resistance. After LTD, voltage sag during hyperpolarizing current injections and subthreshold resonance frequency were decreased. All changes were blocked by ZD7288 (4-ethylphenylamino-1,2-dimethyl-6-methylaminopyrimidinium chloride), suggesting that a physiological loss of dendritic h-channels was responsible for the increase in excitability. Furthermore, block of group 1 metabotropic glutamate receptors (mGluRs) or protein kinase C prevented the increase in excitability, whereas the group 1 mGluR agonist DHPG [(RS)-3,5-dihydroxyphenylglycine] mimicked the effects. We conclude that 3 Hz synaptic stimulation downregulates Ih via activation of group 1 mGluRs and subsequent stimulation of protein kinase C. We propose these changes as part of a homeostatic and bidirectional control mechanism for intrinsic excitability during learning. 10.1523/JNEUROSCI.3520-07.2007 Plasticity of Intrinsic Excitability during Long-Term Depression Is Mediated through mGluR-Dependent Changes in Ih in Hippocampal CA1 Pyramidal Neurons Darrin Brager Daniel Johnston doi:10.1523/JNEUROSCI.3520-07.2007 J. Neurosci., Vol. 27, No. 51. (19 December 2007), pp. 13926-13937. 2008-01-09T11:51:37-00:00 2007 J. Neurosci. 27 51 13926 13937 h-current hippocampus ltd http://www.citeulike.org/user/starz1010101/article/2795821 <i>Journal of neurophysiology, Vol. 90, No. 4. (October 2003), pp. 2428-2437.</i><br /><br />Layer V pyramidal cells of the somatosensory cortex operate with two spike initiation zones. Subthreshold depolarizations are strongly attenuated along the apical dendrite linking the somatic and distal dendritic spike initiation zones. Sodium action potentials, on the other hand, are actively back-propagating from the axon hillock into the apical tuft. There they can interact with local excitatory input leading to the generation of calcium action potentials. We investigated if and how back-propagating sodium action potentials alone, without concomitant excitatory dendritic input, can initiate calcium action potentials in the distal dendrite. In acute slices of the rat somatosensory cortex, layer V pyramidal cells were studied under current-clamp with simultaneous recordings from the soma and the apical dendrite. A train of four somatic action potentials had to reach high frequencies to induce calcium action potentials in the dendrite ("critical frequency," CF approximately 100 Hz). Depolarization in the dendrite reduced the CF, while hyperpolarization increased it. The CF depended on the presence of the hyperpolarization-activated current Ih: blockade with 20 microM 4-(N-ethyl-N-phenylamino)-1,2-dimethyl-6-(methylamino) pyridinium chloride (ZD7288) reduced the CF to 68% of control. If the neurons were stimulated with noisy current injections, leading to in-vivo-like irregular spiking, no calcium action potentials were induced in the dendrite. However, after Ih channel blockade, calcium action potentials were frequently seen. These data suggest that Ih prevents initiation of the dendritic calcium action potential by proximal input alone. Dendritic calcium action potentials may therefore represent a unique signature for coincident somatic and dendritic activation. Hyperpolarization-activated current Ih disconnects somatic and dendritic spike initiation zones in layer V pyramidal neurons. T Berger W Senn HR Lüscher doi:10.1152/jn.00377.2003 Journal of neurophysiology, Vol. 90, No. 4. (October 2003), pp. 2428-2437. 2008-05-13T18:15:45-00:00 2003 Journal of neurophysiology 0022-3077 90 4 2428 2437 dendrites h-current http://www.citeulike.org/user/starz1010101/article/2365492 <i>J Neurophysiol, Vol. 99, No. 1. (1 January 2008), pp. 394-401.</i><br /><br />Although dendritic spikes are generally thought to be restricted to the distal apical dendrite, we know very little about the possible modulatory mechanisms that set the spatial limits of dendritic spikes. Our experiments demonstrated that high-frequency trains of backpropagating action potentials avoided filtering in the apical dendrite and initiated all-or-none dendritic Ca2+ transients associated with dendritic spikes in layer 5 pyramidal neurons of the prefrontal cortex. The block of hyperpolarization-activated currents (Ih) by ZD7288 could shift the frequency threshold and decreased the number of action potentials required to produce the all-or-none Ca2+ transient. Activation of alpha2-adrenergic receptors could also shift the frequency domain of spike induction to lower frequencies. Our data suggest that noradrenergic activity in the prefrontal cortex influences dendritic Ih and extends the zone of dendritic spikes in the apical dendrite via alpha2-adrenergic receptors. This mechanism might be one cellular correlate of the alpha2-receptormediated actions on working memory. 10.1152/jn.00943.2007 alpha2-Adrenergic Receptors Modify Dendritic Spike Generation Via HCN Channels in the Prefrontal Cortex Albert Barth Sylvester Vizi Tibor Zelles Balazs Lendvai doi:10.1152/jn.00943.2007 J Neurophysiol, Vol. 99, No. 1. (1 January 2008), pp. 394-401. 2008-02-12T10:24:02-00:00 2008 J Neurophysiol 99 1 394 401 2pe ca_phys critical_frequency dendrites hcn h-current pfc http://www.citeulike.org/user/starz1010101/article/2265584 <i>Neuron, Vol. 56, No. 6. (20 December 2007), pp. 1076-1089.</i><br /><br />Summary HCN1 hyperpolarization-activated cation channels act as an inhibitory constraint of both spatial learning and synaptic integration and long-term plasticity in the distal dendrites of hippocampal CA1 pyramidal neurons. However, as HCN1 channels provide an excitatory current, the mechanism of their inhibitory action remains unclear. Here we report that HCN1 channels also constrain CA1 distal dendritic Ca2+ spikes, which have been implicated in the induction of LTP at distal excitatory synapses. Our experimental and computational results indicate that HCN1 channels provide both an active shunt conductance that decreases the temporal integration of distal EPSPs and a tonic depolarizing current that increases resting inactivation of T-type and N-type voltage-gated Ca2+ channels, which contribute to the Ca2+ spikes. This dual mechanism may provide a general means by which HCN channels regulate dendritic excitability. HCN1 Channels Constrain Synaptically Evoked Ca2+ Spikes in Distal Dendrites of CA1 Pyramidal Neurons David Tsay Joshua Dudman Steven Siegelbaum doi:10.1016/j.neuron.2007.11.015 Neuron, Vol. 56, No. 6. (20 December 2007), pp. 1076-1089. 2008-01-21T04:05:42-00:00 2007 Neuron 56 6 1076 1089 hcn h-current inpjc lab_meeting ltp http://www.citeulike.org/user/starz1010101/article/1255226 <i>Cell, Vol. 129, No. 2. (20 April 2007), pp. 397-410.</i><br /><br />Spatial working memory (WM; i.e., "scratchpad" memory) is constantly updated to guide behavior based on representational knowledge of spatial position. It is maintained by spatially tuned, recurrent excitation within networks of prefrontal cortical (PFC) neurons, evident during delay periods in WM tasks. Stimulation of postsynaptic alpha2A adrenoceptors (alpha2A-ARs) is critical for WM. We report that alpha2A-AR stimulation strengthens WM through inhibition of cAMP, closing Hyperpolarization-activated Cyclic Nucleotide-gated (HCN) channels and strengthening the functional connectivity of PFC networks. Ultrastructurally, HCN channels and alpha2A-ARs were colocalized in dendritic spines in PFC. In electrophysiological studies, either alpha2A-AR stimulation, cAMP inhibition or HCN channel blockade enhanced spatially tuned delay-related firing of PFC neurons. Conversely, delay-related network firing collapsed under conditions of excessive cAMP. In behavioral studies, either blockade or knockdown of HCN1 channels in PFC improved WM performance. These data reveal a powerful mechanism for rapidly altering the strength of WM networks in PFC. alpha2A-Adrenoceptors Strengthen Working Memory Networks by Inhibiting cAMP-HCN Channel Signaling in Prefrontal Cortex. M Wang BP Ramos CD Paspalas Y Shu A Simen A Duque S Vijayraghavan A Brennan A Dudley E Nou JA Mazer DA McCormick AF Arnsten doi:10.1016/j.cell.2007.03.015 Cell, Vol. 129, No. 2. (20 April 2007), pp. 397-410. 2007-04-26T08:51:59-00:00 2007 Cell 0092-8674 129 2 397 410 hcn h-current pfc working_memory http://www.citeulike.org/user/starz1010101/article/1061730 <i>Neuron, Vol. 21, No. 1. (July 1998), pp. 9-12.</i> H-current: properties of a neuronal and network pacemaker. A Lüthi DA McCormick Neuron, Vol. 21, No. 1. (July 1998), pp. 9-12. 2007-01-23T08:25:58-00:00 1998 Neuron 0896-6273 21 1 9 12 h-current oscillation review