@article {48008, title = {Illuminating the neuronal architecture underlying context in fear memory.}, journal = {Cell}, volume = {167}, year = {2016}, month = {2016 Nov 3}, pages = {888-9}, abstract = {

Context plays a foundational role in determining how to interpret potentially fear-producing stimuli, yet the precise neurobiological substrates of context are poorly understood. In this issue of Cell, Xu et\ al. elegantly show that parallel neuronal circuits are necessary for two distinct roles of context in fear conditioning.

}, author = {Cembrowski, Mark S and Spruston, N} } @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 {45890, title = {Dichotomy of action-potential backpropagation in CA1 pyramidal neuron dendrites.}, journal = {J Neurophysiol}, volume = {86}, year = {2001}, month = {2001 Dec}, pages = {2998-3010}, abstract = {

In hippocampal CA1 pyramidal neurons, action potentials are typically initiated in the axon and backpropagate into the dendrites, shaping the integration of synaptic activity and influencing the induction of synaptic plasticity. Despite previous reports describing action-potential propagation in the proximal apical dendrites, the extent to which action potentials invade the distal dendrites of CA1 pyramidal neurons remains controversial. Using paired somatic and dendritic whole cell recordings, we find that in the dendrites proximal to 280 microm from the soma, single backpropagating action potentials exhibit \<50\% attenuation from their amplitude in the soma. However, in dendritic recordings distal to 300 microm from the soma, action potentials in most cells backpropagated either strongly (26-42\% attenuation; n = 9/20) or weakly (71-87\% attenuation; n = 10/20) with only one cell exhibiting an intermediate value (45\% attenuation). In experiments combining dual somatic and dendritic whole cell recordings with calcium imaging, the amount of calcium influx triggered by backpropagating action potentials was correlated with the extent of action-potential invasion of the distal dendrites. Quantitative morphometric analyses revealed that the dichotomy in action-potential backpropagation occurred in the presence of only subtle differences in either the diameter of the primary apical dendrite or branching pattern. In addition, action-potential backpropagation was not dependent on a number of electrophysiological parameters (input resistance, resting potential, voltage sensitivity of dendritic spike amplitude). There was, however, a striking correlation of the shape of the action potential at the soma with its amplitude in the dendrite; larger, faster-rising, and narrower somatic action potentials exhibited more attenuation in the distal dendrites (300-410 microm from the soma). Simple compartmental models of CA1 pyramidal neurons revealed that a dichotomy in action-potential backpropagation could be generated in response to subtle manipulations of the distribution of either sodium or potassium channels in the dendrites. Backpropagation efficacy could also be influenced by local alterations in dendritic side branches, but these effects were highly sensitive to model parameters. Based on these findings, we hypothesize that the observed dichotomy in dendritic action-potential amplitude is conferred primarily by differences in the distribution, density, or modulatory state of voltage-gated channels along the somatodendritic axis.

}, keywords = {Action Potentials, Animals, Calcium, Dendrites, Diagnostic Imaging, Electrophysiology, Fluorescent Dyes, Fura-2, Hippocampus, In Vitro Techniques, Male, Models, Neurological, Patch-Clamp Techniques, Potassium Channels, Pyramidal Cells, Rats, Rats, Wistar, Sodium Channels}, issn = {0022-3077}, author = {Golding, N L and Kath, W L and Spruston, N} } @article {45914, title = {Diversity and dynamics of dendritic signaling.}, journal = {Science}, volume = {290}, year = {2000}, month = {2000 Oct 27}, pages = {739-44}, abstract = {

Communication between neurons in the brain occurs primarily through synapses made onto elaborate treelike structures called dendrites. New electrical and optical recording techniques have led to tremendous advances in our understanding of how dendrites contribute to neuronal computation in the mammalian brain. The varied morphology and electrical and chemical properties of dendrites enable a spectrum of local and long-range signaling, defining the input-output relationship of neurons and the rules for induction of synaptic plasticity. In this way, diversity in dendritic signaling allows individual neurons to carry out specialized functions within their respective networks.

}, keywords = {Action Potentials, Animals, Brain, Calcium Signaling, Dendrites, Electrophysiology, Humans, Ion Channel Gating, Ion Channels, Neuronal Plasticity, Neurons, Neurotransmitter Agents, Protein Biosynthesis, Signal Transduction, Synapses, Synaptic Transmission}, issn = {0036-8075}, author = {H{\"a}usser, M and Spruston, N and Stuart, G J} } @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 {45908, title = {Dendritic sodium spikes are variable triggers of axonal action potentials in hippocampal CA1 pyramidal neurons.}, journal = {Neuron}, volume = {21}, year = {1998}, month = {1998 Nov}, pages = {1189-200}, abstract = {

Several early studies suggested that spikes can be generated in the dendrites of CA1 pyramidal neurons, but their functional significance and the conditions under which they occur remain poorly understood. Here, we provide direct evidence from simultaneous dendritic and somatic patch-pipette recordings that excitatory synaptic inputs can elicit dendritic sodium spikes prior to axonal action potential initiation in hippocampal CA1 pyramidal neurons. Both the probability and amplitude of dendritic spikes depended on the previous synaptic and firing history of the cell. Moreover, some dendritic spikes occurred in the absence of somatic action potentials, indicating that their propagation to the soma and axon is unreliable. We show that dendritic spikes contribute a variable depolarization that summates with the synaptic potential and can act as a trigger for action potential initiation in the axon.

}, keywords = {Action Potentials, Animals, Axons, Dendrites, Electric Stimulation, Hippocampus, In Vitro Techniques, Male, Neurons, Patch-Clamp Techniques, Pyramidal Cells, Rats, Rats, Wistar, Sodium, Sodium Channels, Synapses}, issn = {0896-6273}, author = {Golding, N L and Spruston, N} } @article {45912, title = {Determinants of voltage attenuation in neocortical pyramidal neuron dendrites.}, journal = {J Neurosci}, volume = {18}, year = {1998}, month = {1998 May 15}, pages = {3501-10}, abstract = {

How effectively synaptic and regenerative potentials propagate within neurons depends critically on the membrane properties and intracellular resistivity of the dendritic tree. These properties therefore are important determinants of neuronal function. Here we use simultaneous whole-cell patch-pipette recordings from the soma and apical dendrite of neocortical layer 5 pyramidal neurons to directly measure voltage attenuation in cortical neurons. When combined with morphologically realistic compartmental models of the same cells, the data suggest that the intracellular resistivity of neocortical pyramidal neurons is relatively low ( approximately 70 to 100 Omegacm), but that voltage attenuation is substantial because of nonuniformly distributed resting conductances present at a higher density in the distal apical dendrites. These conductances, which were largely blocked by bath application of CsCl (5 mM), significantly increased steady-state voltage attenuation and decreased EPSP integral and peak in a manner that depended on the location of the synapse. Together these findings suggest that nonuniformly distributed Cs-sensitive and -insensitive resting conductances generate a "leaky" apical dendrite, which differentially influences the integration of spatially segregated synaptic inputs.

}, keywords = {Animals, Cesium, Chlorides, Computer Simulation, Dendrites, Electric Conductivity, Electric Impedance, Excitatory Postsynaptic Potentials, Membrane Potentials, Models, Neurological, Neocortex, Patch-Clamp Techniques, Pyramidal Cells, Rats, Rats, Wistar}, issn = {0270-6474}, author = {Stuart, G and Spruston, N} } @article {45896, title = {Specialized electrophysiological properties of anatomically identified neurons in the hilar region of the rat fascia dentata.}, journal = {J Neurophysiol}, volume = {79}, year = {1998}, month = {1998 Mar}, pages = {1518-34}, abstract = {

Because of their strategic position between the granule cell and pyramidal cell layers, neurons of the hilar region of the hippocampal formation are likely to play an important role in the information processing between the entorhinal cortex and the hippocampus proper. Here we present an electrophysiological characterization of anatomically identified neurons in the fascia dentata as studied using patch-pipette recordings and subsequent biocytin-staining of neurons in slices. The resting potential, input resistance (RN), membrane time constant (taum), "sag" in hyperpolarizing responses, maximum firing rate during a 1-s current pulse, spike width, and fast and slow afterhyperpolarizations (AHPs) were determined for several different types of hilar neurons. Basket cells had a dense axonal plexus almost exclusively within the granule cell layer and were distinguishable by their low RN, short taum, lack of sag, and rapid firing rates. Dentate granule cells also lacked sag and were identifiable by their higher RN, longer taum, and lower firing rates than basket cells. Mossy cells had extensive axon collaterals within the hilus and a few long-range collaterals to the inner molecular layer and CA3c and were characterized physiologically by small fast and slow AHPs. Spiny and aspiny hilar interneurons projected primarily either to the inner or outer segment of the molecular layer and had a dense intrahilar axonal plexus, terminating onto somata within the hilus and CA3c. Physiologically, spiny hilar interneurons generally had higher RN values than mossy cells and a smaller slow AHP than aspiny interneurons. The specialized physiological properties of different classes of hilar neurons are likely to be important determinants of their functional operation within the hippocampal circuitry.

}, keywords = {Animals, Axons, Dendrites, Dentate Gyrus, Electrophysiology, In Vitro Techniques, Interneurons, Membrane Potentials, Microscopy, Video, Neurons, Rats, Rats, Wistar, Regression Analysis}, issn = {0022-3077}, author = {L{\"u}bke, J and Frotscher, M and Spruston, N} } @article {45923, title = {Action potential initiation and backpropagation in neurons of the mammalian CNS.}, journal = {Trends Neurosci}, volume = {20}, year = {1997}, month = {1997 Mar}, pages = {125-31}, abstract = {

Most neurons in the mammalian CNS encode and transmit information via action potentials. Knowledge of where these electrical events are initiated and how they propagate within neurons is therefore fundamental to an understanding of neuronal function. While work from the 1950s suggested that action potentials are initiated in the axon, many subsequent investigations have suggested that action potentials can also be initiated in the dendrites. Recently, experiments using simultaneous patch-pipette recordings from different locations on the same neuron have been used to address this issue directly. These studies show that the site of action potential initiation is in the axon, even when synaptic activation is powerful enough to elicit dendritic electrogenesis. Furthermore, these and other studies also show that following initiation, action potentials actively backpropagate into the dendrites of many neuronal types, providing a retrograde signal of neuronal output to the dendritic tree.

}, keywords = {Action Potentials, Animals, Central Nervous System, Neurons}, issn = {0166-2236}, author = {Stuart, G and Spruston, N and Sakmann, B and H{\"a}usser, M} } @article {45903, title = {Interneurons in the stratum lucidum of the rat hippocampus: an anatomical and electrophysiological characterization.}, journal = {J Comp Neurol}, volume = {385}, year = {1997}, month = {1997 Sep 1}, pages = {427-40}, abstract = {

The anatomical and electrophysiological properties of neurons in the stratum lucidum of the CA3 subfield of the hippocampus were examined by using patch-pipette recordings combined with biocytin staining. This method facilitated the analysis of the morphological features and passive and active properties of a recently described class of spiny neurons in the stratum lucidum, as well as aspiny neurons in this region. Some, but not all, synaptic inputs of both types of neurons were found to arise from the mossy fiber system. The axons of spiny neurons in the stratum lucidum were heavily collateralized, terminating primarily in the stratum lucidum and stratum radiatum of CA3, and to a lesser extent in the stratum pyramidale and stratum oriens. Only a few axonal projections were found that extended beyond the CA3 region into CA1 and the hilus. Aspiny neurons fell into two classes: those projecting axons to the stratum lucidum and stratum radiatum of CA3 and those with axon terminations mainly in the stratum pyramidale and stratum oriens. The electrophysiological properties of spiny and aspiny neurons in the stratum lucidum were similar, but on average, the aspiny neurons had significantly higher maximal firing rates and narrower action potential half-widths. The results demonstrate that a diverse population of neurons exists in the region of mossy fiber termination in area CA3. These neurons may be involved in local-circuit feedback, or feed-forward systems controlling the flow of information through the hippocampus.

}, keywords = {Animals, Axons, Dendrites, Hippocampus, Interneurons, Neurons, Patch-Clamp Techniques, Rats, Rats, Wistar, Synapses, Synaptic Transmission}, issn = {0021-9967}, author = {Spruston, N and L{\"u}bke, J and Frotscher, M} } @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} } @article {45913, title = {Activity-dependent action potential invasion and calcium influx into hippocampal CA1 dendrites.}, journal = {Science}, volume = {268}, year = {1995}, month = {1995 Apr 14}, pages = {297-300}, abstract = {

The temporal and spatial profile of activity-evoked changes in membrane potential and intracellular calcium concentration in the dendrites of hippocampal CA1 pyramidal neurons was examined with simultaneous somatic and dendritic patch-pipette recording and calcium imaging experiments. Action potentials are initiated close to the soma of these neurons and backpropagate into the dendrites in an activity-dependent manner; those occurring early in a train propagate actively, whereas those occurring later fail to actively invade the distal dendrites. Consistent with this finding, dendritic calcium transients evoked by single action potentials do not significantly attenuate with distance from the soma, whereas those evoked by trains attenuate substantially. Failure of action potential propagation into the distal dendrites often occurs at branch points. Consequently, neighboring regions of the dendritic tree can experience different voltage and calcium signals during repetitive action potential firing. The influence of backpropagating action potentials on synaptic integration and plasticity will therefore depend on both the extent of dendritic branching and the pattern of neuronal activity.

}, keywords = {Action Potentials, Animals, Calcium, Calcium Channels, Dendrites, Ion Channel Gating, Neuronal Plasticity, Patch-Clamp Techniques, Pyramidal Cells, Rats, Rats, Wistar, Sodium Channels, Synapses, Tetrodotoxin}, issn = {0036-8075}, author = {Spruston, N and Schiller, Y and Stuart, G and Sakmann, B} } @article {45893, title = {Dendritic glutamate receptor channels in rat hippocampal CA3 and CA1 pyramidal neurons.}, journal = {J Physiol}, volume = {482 ( Pt 2)}, year = {1995}, month = {1995 Jan 15}, pages = {325-52}, abstract = {

1. Properties of dendritic glutamate receptor (GluR) channels were investigated using fast application of glutamate to outside-out membrane patches isolated from the apical dendrites of CA3 and CA1 pyramidal neurons in rat hippocampal slices. CA3 patches were formed (15-76 microns from the soma) in the region of mossy fibre (MF) synapses, and CA1 patches (25-174 microns from the soma) in the region of Schaffer collateral (SC) innervation. 2. Dual-component responses consisting of a rapidly rising and decaying component followed by a second, substantially slower, component were elicited by 1 ms pulses of 1 mM glutamate in the presence of 10 microM glycine and absence of external Mg2+. The fast component was selectively blocked by 2-5 microM 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX) and the slow component by 30 microM D-2-amino-5-phosphonopentanoic acid (D-AP5), suggesting that the fast and slow components were mediated by the GluR channels of the L-alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionate (AMPA) and NMDA type, respectively. The peak amplitude ratio of the NMDA to AMPA receptor-mediated components varied between 0.03 and 0.62 in patches from both CA3 and CA1 dendrites. Patches lacking either component were rarely observed. 3. The peak current-voltage (I-V) relationship of the fast component was almost linear, whereas the I-V relationship of the slow component showed a region of negative slope in the presence of 1 mM external Mg2+. The reversal potential for both components was close to 0 mV. 4. Kainate-preferring GluR channels did not contribute appreciably to the response to glutamate. The responses to 100 ms pulses of 1 mM glutamate were mimicked by application of 1 mM AMPA, whereas 1 mM kainate produced much smaller, weakly desensitizing currents. This suggests that the fast component is primarily mediated by the action of glutamate on AMPA-preferring receptors. 5. The mean elementary conductance of AMPA receptor channels was about 10 pS, as estimated by non-stationary fluctuation analysis. The permeability of these channels to Ca2+ was low (approximately 5\% of the permeability to Cs+). 6. The elementary conductance of NMDA receptor channels was larger, with a main conductance state of about 45 pS. These channels were 3.6 times more permeable to Ca2+ than to Cs+.(ABSTRACT TRUNCATED AT 400 WORDS)

}, keywords = {2-Amino-5-phosphonovalerate, 6-Cyano-7-nitroquinoxaline-2,3-dione, alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid, Animals, Calcium, Cell Membrane Permeability, Dendrites, Electric Conductivity, Hippocampus, Kainic Acid, Magnesium, Patch-Clamp Techniques, Pyramidal Cells, Rats, Rats, Wistar, Receptors, AMPA, Receptors, N-Methyl-D-Aspartate, Time Factors, Zinc}, issn = {0022-3751}, author = {Spruston, N and Jonas, P and Sakmann, B} } @article {45892, title = {Probing dendritic function with patch pipettes.}, journal = {Curr Opin Neurobiol}, volume = {5}, year = {1995}, month = {1995 Jun}, pages = {389-94}, abstract = {

Most neurons in the CNS have complex, branching dendritic trees, which receive the majority of all synaptic input. As it is difficult to make electrical recordings from dendrites because of their small size, most of what is known about their electrical properties has been inferred from recordings made at the soma. By taking advantage of the higher resolution offered by improved optics, it is now possible to make patch-pipette recordings from the dendrites of neurons in brain slices under visual control. This new technique promises to provide valuable new information concerning dendritic function.

}, keywords = {Animals, Dendritic Cells, Electrophysiology, Hippocampus, Patch-Clamp Techniques}, issn = {0959-4388}, author = {Stuart, G and Spruston, N} } @article {45897, title = {Dendritic attenuation of synaptic potentials and currents: the role of passive membrane properties.}, journal = {Trends Neurosci}, volume = {17}, year = {1994}, month = {1994 Apr}, pages = {161-6}, abstract = {

The dendritic trees of neurons are structurally and functionally complex integrative units receiving thousands of synaptic inputs that have excitatory and inhibitory, fast and slow, and electrical and biochemical effects. The pattern of activation of these synaptic inputs determines if the neuron will fire an action potential at any given point in time and how it will respond to similar inputs in the future. Two critical factors affect the integrative function of dendrites: the distribution of voltage-gated ion channels in the dendritic tree and the passive electrical properties, or {\textquoteright}electrotonic structure{\textquoteright}, upon which these active channels are superimposed. The authors review recent data from patch-clamp recordings that provide new estimates of the passive membrane properties of hippocampal neurons, and show, with examples, how these properties affect the shaping and attenuation of synaptic potentials as they propagate in the dendrites, as well as how they affect the measurement of current from synapses located in the dendrites. Voltage-gated channels might influence the measurement of {\textquoteright}passive{\textquoteright} membrane properties and, reciprocally, passive membrane properties might affect the activation of voltage-gated channels in dendrites.

}, keywords = {Animals, Cell Membrane, Dendrites, Hippocampus, Ion Channel Gating, Neurons, Rats, Synaptic Transmission}, issn = {0166-2236}, author = {Spruston, N and Jaffe, D B and Johnston, D} } @article {45929, title = {Mechanisms shaping glutamate-mediated excitatory postsynaptic currents in the CNS.}, journal = {Curr Opin Neurobiol}, volume = {4}, year = {1994}, month = {1994 Jun}, pages = {366-72}, abstract = {

Excitatory postsynaptic currents in neurones of the central nervous system have a dual-component time course that results from the co-activation of AMPA/kainate-type and NMDA-type glutamate receptors. New approaches in electrophysiology and molecular biology have provided a better understanding of the factors that determine the kinetics of excitatory postsynaptic currents. Recent studies suggest that the time course of neurotransmitter concentration in the synaptic cleft, the gating properties of the native channels, and the glutamate receptor subunit composition all appear to be important factors.

}, keywords = {Animals, Central Nervous System, Electrophysiology, Glutamic Acid, Humans, Ion Channels, Kinetics, Receptors, AMPA, Receptors, Glutamate, Receptors, Kainic Acid, Synapses}, issn = {0959-4388}, author = {Jonas, P and Spruston, N} } @article {45933, title = {Voltage- and space-clamp errors associated with the measurement of electrotonically remote synaptic events.}, journal = {J Neurophysiol}, volume = {70}, year = {1993}, month = {1993 Aug}, pages = {781-802}, abstract = {

1. The voltage- and space-clamp errors associated with the use of a somatic electrode to measure current from dendritic synapses are evaluated using both equivalent-cylinder and morphologically realistic models of neuronal dendritic trees. 2. As a first step toward understanding the properties of synaptic current distortion under voltage-clamp conditions, the attenuation of step and sinusoidal voltage changes are evaluated in equivalent cylinder models. Demonstration of the frequency-dependent attenuation of voltage in the cable is then used as a framework for understanding the distortion of synaptic currents generated at sites remote from the somatic recording electrode and measured in the voltage-clamp recording configuration. 3. Increases in specific membrane resistivity (Rm) are shown to reduce steady-state voltage attenuation, while producing only minimal reduction in attenuation of transient voltage changes. Experimental manipulations that increase Rm therefore improve the accuracy of estimates of reversal potential for electrotonically remote synapses, but do not significantly reduce the attenuation of peak current. In addition, increases in Rm have the effect of slowing the kinetics of poorly clamped synaptic currents. 4. The effects of the magnitude of the synaptic conductance and its kinetics on the measured synaptic currents are also examined and discussed. The error in estimating parameters from measured synaptic currents is greatest for synapses with fast kinetics and large conductances. 5. A morphologically realistic model of a CA3 pyramidal neuron is used to demonstrate the generality of the conclusions derived from equivalent cylinder models. The realistic model is also used to fit synaptic currents generated by stimulation of mossy fiber (MF) and commissural/associational (C/A) inputs to CA3 neurons and to estimate the amount of distortion of these measured currents. 6. Anatomic data from the CA3 pyramidal neuron model are used to construct a simplified two-cylinder CA3 model. This model is used to estimate the electrotonic distances of MF synapses (which are located proximal to the soma) and perforant path (PP) synapses (which are located at the distal ends of the apical dendrites) and the distortion of synaptic current parameters measured for these synapses. 7. Results from the equivalent-cylinder models, the morphological CA3 model, and the simplified CA3 model all indicate that the amount of distortion of synaptic currents increases steeply as a function of distance from the soma. MF synapses close to the soma are likely to be subject only to small space-clamp errors, whereas MF synapses farther from the soma are likely to be substantially attenuated.(ABSTRACT TRUNCATED AT 400 WORDS)

}, keywords = {Animals, Dendrites, Guinea Pigs, Hippocampus, Membrane Potentials, Models, Neurological, Neural Conduction, Neurons, Synapses, Synaptic Transmission}, issn = {0022-3077}, author = {Spruston, N and Jaffe, D B and Williams, S H and Johnston, D} } @article {45902, title = {Perforated patch-clamp analysis of the passive membrane properties of three classes of hippocampal neurons.}, journal = {J Neurophysiol}, volume = {67}, year = {1992}, month = {1992 Mar}, pages = {508-29}, abstract = {

1. Perforated patch-clamp recordings were made from the three major classes of hippocampal neurons in conventional in vitro slices prepared from adult guinea pigs. This technique provided experimental estimates of passive membrane properties (input resistance, RN, and membrane time constant, tau m) determined in the absence of the leak conductance associated with microelectrode impalement or the washout of cytoplasmic constituents associated with conventional whole-cell recordings. 2. To facilitate comparison of our data with previous results and to determine the passive membrane properties under conditions as physiological as possible, recordings were made at the resting potential, in physiological saline, and without any added blockers of voltage-dependent conductances. 3. Membrane-potential responses to current steps were analyzed, and four criteria were used to identify voltage responses that were the least affected by activation of voltage-dependent conductances. tau m was estimated from the slowest component (tau 0) of multiexponential fits of responses deemed passive by these criteria. RN was estimated from the slope of the linear region in the hyperpolarizing direction of the voltage-current relation. 4. It was not possible to measure purely passive membrane properties that were completely independent of membrane potential in any of the three classes of hippocampal neurons. Changing the membrane potential by constant current injection resulted in changes in RN and tau 0; subthreshold depolarization produced an increase, and hyperpolarization a decrease, in both RN and tau 0 for all three classes of hippocampal neurons. 5. Each of the three classes of hippocampal neurons also displayed a depolarizing "sag" during larger hyperpolarizing voltage transients. To evaluate the effect of the conductances underlying this sag on passive membrane properties, 2-5 mM Cs+ was added to the physiological saline. Extracellular Cs+ effectively blocked the sag in all three classes of hippocampal neurons, but the effect of Cs+ on RN, tau 0, and the voltage dependence of these parameters was unique for each class of neurons. 6. CA1 pyramidal neurons had an RN of 104 +/- 10 (SE) M omega and tau 0 of 28 +/- 2 ms at a resting potential of -64 +/- 2 mV (n = 12). RN and tau 0 were larger at more depolarized potentials in these neurons, but the addition of Cs+ to the physiological saline reversed this voltage dependence. 7. CA3 pyramidal neurons had an RN of 135 +/- 8 M omega and tau 0 of 66 +/- 4 ms at a resting potential of -64 +/- 1 mV (n = 14).(ABSTRACT TRUNCATED AT 400 WORDS)

}, keywords = {Animals, Cesium, Electrophysiology, Guinea Pigs, Hippocampus, In Vitro Techniques, Membrane Potentials, Membranes, Microelectrodes, Neurons, Pyramidal Tracts}, issn = {0022-3077}, author = {Spruston, N and Johnston, D} }