@article {45927, title = {Action potential bursting in subicular pyramidal neurons is driven by a calcium tail current.}, journal = {J Neurosci}, volume = {21}, year = {2001}, month = {2001 May 15}, pages = {3312-21}, abstract = {

Subiculum is the primary output area of the hippocampus and serves as a key relay center in the process of memory formation and retrieval. A majority of subicular pyramidal neurons communicate via bursts of action potentials, a mode of signaling that may enhance the fidelity of information transfer and synaptic plasticity or contribute to epilepsy when unchecked. In the present study, we show that a Ca(2+) tail current drives bursting in subicular pyramidal neurons. An action potential activates voltage-activated Ca(2+) channels, which deactivate slowly enough during action potential repolarization to produce an afterdepolarization that triggers subsequent action potentials in the burst. The Ca(2+) channels underlying bursting are located primarily near the soma, and the amplitude of Ca(2+) tail currents correlates with the strength of bursting across cells. Multiple channel subtypes contribute to Ca(2+) tail current, but the need for an action potential to produce the slow depolarization suggests a central role for high-voltage-activated Ca(2+) channels in subicular neuron bursting.

}, keywords = {Action Potentials, Animals, Calcium, Calcium Channel Blockers, Calcium Channels, T-Type, Dendrites, Dose-Response Relationship, Drug, Electric Stimulation, Fluorescent Dyes, Fura-2, Hippocampus, In Vitro Techniques, Microelectrodes, Microinjections, Nickel, Patch-Clamp Techniques, Perfusion, Potassium Channels, Pyramidal Cells, Rats, Sodium Channels, Tetrodotoxin}, issn = {1529-2401}, author = {Jung, H Y and Staff, N P and Spruston, N} } @article {45925, title = {Resting and active properties of pyramidal neurons in subiculum and CA1 of rat hippocampus.}, journal = {J Neurophysiol}, volume = {84}, year = {2000}, month = {2000 Nov}, pages = {2398-408}, abstract = {

Action potentials are the end product of synaptic integration, a process influenced by resting and active neuronal membrane properties. Diversity in these properties contributes to specialized mechanisms of synaptic integration and action potential firing, which are likely to be of functional significance within neural circuits. In the hippocampus, the majority of subicular pyramidal neurons fire high-frequency bursts of action potentials, whereas CA1 pyramidal neurons exhibit regular spiking behavior when subjected to direct somatic current injection. Using patch-clamp recordings from morphologically identified neurons in hippocampal slices, we analyzed and compared the resting and active membrane properties of pyramidal neurons in the subiculum and CA1 regions of the hippocampus. In response to direct somatic current injection, three subicular firing types were identified (regular spiking, weak bursting, and strong bursting), while all CA1 neurons were regular spiking. Within subiculum strong bursting neurons were found preferentially further away from the CA1 subregion. Input resistance (R(N)), membrane time constant (tau(m)), and depolarizing "sag" in response to hyperpolarizing current pulses were similar in all subicular neurons, while R(N) and tau(m) were significantly larger in CA1 neurons. The first spike of all subicular neurons exhibited similar action potential properties; CA1 action potentials exhibited faster rising rates, greater amplitudes, and wider half-widths than subicular action potentials. Therefore both the resting and active properties of CA1 pyramidal neurons are distinct from those of subicular neurons, which form a related class of neurons, differing in their propensity to burst. We also found that both regular spiking subicular and CA1 neurons could be transformed into a burst firing mode by application of a low concentration of 4-aminopyridine, suggesting that in both hippocampal subfields, firing properties are regulated by a slowly inactivating, D-type potassium current. The ability of all subicular pyramidal neurons to burst strengthens the notion that they form a single neuronal class, sharing a burst generating mechanism that is stronger in some cells than others.

}, keywords = {Action Potentials, Animals, Cell Size, Electric Impedance, Electric Stimulation, Hippocampus, Patch-Clamp Techniques, Periodicity, Pyramidal Cells, Rats, Rats, Wistar, Synapses}, issn = {0022-3077}, author = {Staff, N P and Jung, H Y and Thiagarajan, T and Yao, M and Spruston, N} } @article {45919, title = {Dendritic calcium spike initiation and repolarization are controlled by distinct potassium channel subtypes in CA1 pyramidal neurons.}, journal = {J Neurosci}, volume = {19}, year = {1999}, month = {1999 Oct 15}, pages = {8789-98}, abstract = {

In CA1 pyramidal neurons of the hippocampus, calcium-dependent spikes occur in vivo during specific behavioral states and may be enhanced during epileptiform activity. However, the mechanisms that control calcium spike initiation and repolarization are poorly understood. Using dendritic and somatic patch-pipette recordings, we show that calcium spikes are initiated in the apical dendrites of CA1 pyramidal neurons and drive bursts of sodium-dependent action potentials at the soma. Initiation of calcium spikes at the soma was suppressed in part by potassium channels activated by sodium-dependent action potentials. Low-threshold, putative D-type potassium channels [blocked by 100 microM 4-aminopyridine (4-AP) and 0.5-1 microM alpha-dendrotoxin (alpha-DTX)] played a prominent role in setting a high threshold for somatic calcium spikes, thus restricting initiation to the dendrites. DTX- and 4-AP-sensitive channels were activated during sodium-dependent action potentials and mediated a large component of their afterhyperpolarization. Once initiated, repetitive firing of calcium spikes was limited by activation of putative BK-type calcium-activated potassium channels (blocked by 250 microM tetraethylammonium chloride, 70 nM charybdotoxin, or 100 nM iberiotoxin). Thus, the concerted action of calcium- and voltage-activated potassium channels serves to focus spatially and temporally the membrane depolarization and calcium influx generated by calcium spikes during strong, synchronous network excitation.

}, keywords = {4-Aminopyridine, Action Potentials, Animals, Calcium, Dendrites, Elapid Venoms, Electrophysiology, Hippocampus, Large-Conductance Calcium-Activated Potassium Channels, Male, Potassium Channel Blockers, Potassium Channels, Potassium Channels, Calcium-Activated, Protein Isoforms, Pyramidal Cells, Rats, Rats, Wistar, Sodium, Tetraethylammonium}, issn = {1529-2401}, author = {Golding, N L and Jung, H Y and Mickus, T and Spruston, N} } @article {45928, title = {Properties of slow, cumulative sodium channel inactivation in rat hippocampal CA1 pyramidal neurons.}, journal = {Biophys J}, volume = {76}, year = {1999}, month = {1999 Feb}, pages = {846-60}, abstract = {

Sodium channels in the somata and dendrites of hippocampal CA1 pyramidal neurons undergo a form of long-lasting, cumulative inactivation that is involved in regulating back-propagating action potential amplitude and can influence dendritic excitation. Using cell-attached patch-pipette recordings in the somata and apical dendrites of CA1 pyramidal neurons, we determined the properties of slow inactivation on response to trains of brief depolarizations. We find that the amount of slow inactivation gradually increases as a function of distance from the soma. Slow inactivation is also frequency and voltage dependent. Higher frequency depolarizations increase both the amount of slow inactivation and its rate of recovery. Hyperpolarized resting potentials and larger command potentials accelerate recovery from slow inactivation. We compare this form of slow inactivation to that reported in other cell types, using longer depolarizations, and construct a simplified biophysical model to examine the possible gating mechanisms underlying slow inactivation. Our results suggest that sodium channels can enter slow inactivation rapidly from the open state during brief depolarizations or slowly from a fast inactivation state during longer depolarizations. Because of these properties of slow inactivation, sodium channels will modulate neuronal excitability in a way that depends in a complicated manner on the resting potential and previous history of action potential firing.

}, keywords = {Animals, Electrophysiology, Hippocampus, Ion Channel Gating, Patch-Clamp Techniques, Pyramidal Cells, Rats, Rats, Wistar, Sodium Channels}, issn = {0006-3495}, author = {Mickus, T and Jung, H Y and Spruston, N} } @article {45934, title = {Slow sodium channel inactivation in CA1 pyramidal cells.}, journal = {Ann N Y Acad Sci}, volume = {868}, year = {1999}, month = {1999 Apr 30}, pages = {97-101}, keywords = {Animals, Electrophysiology, Ion Channel Gating, Microscopy, Phase-Contrast, Pyramidal Cells, Rats, Rats, Wistar, Sodium Channels}, issn = {0077-8923}, author = {Mickus, T and Jung, H Y and Spruston, N} } @article {45916, title = {Prolonged sodium channel inactivation contributes to dendritic action potential attenuation in hippocampal pyramidal neurons.}, journal = {J Neurosci}, volume = {17}, year = {1997}, month = {1997 Sep 1}, pages = {6639-46}, abstract = {

During low-frequency firing, action potentials actively invade the dendrites of CA1 pyramidal neurons. At higher firing rates, however, activity-dependent processes result in the attenuation of back-propagating action potentials, and propagation failures occur at some dendritic branch points. We tested two major hypotheses related to this activity-dependent attenuation of back-propagating action potentials: (1) that it is mediated by a prolonged form of sodium channel inactivation and (2) that it is mediated by a persistent dendritic shunt activated by back-propagating action potentials. We found no evidence for a persistent shunt, but we did find that cumulative, prolonged inactivation of sodium channels develops during repetitive action potential firing. This inactivation is significant after a single action potential and continues to develop during several action potentials thereafter, until a steady-state sodium current is established. Recovery from this form of inactivation is much slower than its induction, but recovery can be accelerated by hyperpolarization. The similarity of these properties to the time and voltage dependence of attenuation and recovery of dendritic action potentials suggests that dendritic sodium channel inactivation contributes to the activity dependence of action potential back-propagation in CA1 neurons. Hence, the biophysical properties of dendritic sodium channels will be important determinants of action potential-mediated effects on synaptic integration and plasticity in hippocampal neurons.

}, keywords = {Action Potentials, Animals, Dendrites, Electrophysiology, Hippocampus, In Vitro Techniques, Neurons, Pyramidal Cells, Rats, Rats, Wistar, Sodium Channels, Tetrodotoxin, Time Factors}, issn = {0270-6474}, author = {Jung, H Y and Mickus, T and Spruston, N} }