Dendritic Action Potentials Research Articles

Coincidence detection in pyramidal neurons is tuned by their dendritic branching pattern.

Neurons display a variety of complex dendritic morphologies even within the same class. We examined the relationship between dendritic arborization and the coupling between somatic and dendritic action potential (AP) initiation sites in layer 5 (L5) neocortical pyramidal neurons. Coupling was defined as the relative reduction in threshold for initiation of a dendritic calcium AP due to a coincident back-propagating AP. Simulations based on reconstructions of biocytin-filled cells showed that addition of oblique branches of the main apical dendrite in close proximity to the soma (d < 140 microm) increases the coupling between the apical and axosomatic AP initiation zones, whereas incorporation of distal branches decreases coupling. Experimental studies on L5 pyramids in acute brain slices revealed a highly significant (n = 28, r = 0.63, P < 0.0005) correlation: increasing the fraction of proximal oblique dendrites (d < 140 microm), e.g., from 30 to 60% resulted on average in an increase of the coupling from approximately 35% to almost 60%. We conclude that variation in dendritic arborization may be a key determinant of variability in coupling (49 +/- 17%; range 19-83%; n = 37) and is likely to outweigh the contribution made by variations in active membrane properties. Thus coincidence detection of inputs arriving from different cortical layers is strongly regulated by differences in dendritic arborization.

Neuronal assemblies: single cortical neurons are obedient members of a huge orchestra.

Spontaneous cortical activity of single neurons is often either dismissed as noise, or is regarded as carrying no functional significance and hence is ignored. Our findings suggest that such concepts should be revised. We explored the coherent population activity of neuronal assemblies in primary sensory area in the absence of a sensory input. Recent advances in real-time optical imaging based on voltage-sensitive dyes (VSDI) have facilitated exploration of population activity and its intimate relationship to the activity of individual cortical neurons. It has been shown by in vivo intracellular recordings that the dye signal measures the sum of the membrane potential changes in all the neuronal elements in the imaged area, emphasizing subthreshold synaptic potentials and dendritic action potentials in neuronal arborizations originating from neurons in all cortical layers whose dendrites reach the superficial cortical layers. Thus, the VSDI has allowed us to image the rather illusive activity in neuronal dendrites that cannot be readily explored by single unit recordings. Surprisingly, we found that the amplitude of this type of ongoing subthreshold activity is of the same order of magnitude as evoked activity. We also found that this ongoing activity exhibited high synchronization over many millimeters of cortex. We then investigated the influence of ongoing activity on the evoked response, and showed that the two interact strongly. Furthermore, we found that cortical states that were previously associated only with evoked activity can actually be observed also in the absence of stimulation, for example, the cortical representation of a given orientation may appear without any visual input. This demonstration suggests that ongoing activity may also play a major role in other cortical function by providing a neuronal substrate for the dependence of sensory information processing on context, behavior, memory and other aspects of cognitive function.

Effects of short-term synaptic plasticity in a local microcircuit on cell firing

Effects of short-term synaptic plasticity on cell firing properties in a microcircuit formed by a reciprocally connected pyramidal cell and FSN interneuron in layer 2/3 of neocortex were analyzed in a biophysical model. Induction of synaptic depression by backpropagating dendritic action potentials was replicated, as well as the resulting time dependent depression of IPSP amplitudes. Results indicate that the effect of the depression becomes significant above 30 Hz input frequency. The magnitude of the effect depends on the time constant of the dendritic calcium regulating the depression. The frequency range depends on the time constant of the IPSP.

D型Kチャネルの特性変化がシナプス信号統合に与える影響 : コンピュータシミュレーションよる解析

D型Kチャネルの特性変化がシナプス信号統合に与える影響 : コンピュータシミュレーションよる解析

Inhibition of backpropagating action potentials in mitral cell secondary dendrites.

The mammalian olfactory bulb is a geometrically organized signal-processing array that utilizes lateral inhibitory circuits to transform spatially patterned inputs. A major part of the lateral circuitry consists of extensively radiating secondary dendrites of mitral cells. These dendrites are bidirectional cables: they convey granule cell inhibitory input to the mitral soma, and they conduct backpropagating action potentials that trigger glutamate release at dendrodendritic synapses. This study examined how mitral cell firing is affected by inhibitory inputs at different distances along the secondary dendrite and what happens to backpropagating action potentials when they encounter inhibition. These are key questions for understanding the range and spatial dependence of lateral signaling between mitral cells. Backpropagating action potentials were monitored in vitro by simultaneous somatic and dendritic whole cell recording from individual mitral cells in rat olfactory bulb slices, and inhibition was applied focally to dendrites by laser flash photolysis of caged GABA (2.5-microm spot). Photolysis was calibrated to activate conductances similar in magnitude to GABA(A)-mediated inhibition from granule cell spines. Under somatic voltage-clamp with CsCl dialysis, uncaging GABA onto the soma, axon initial segment, primary and secondary dendrites evoked bicuculline-sensitive currents (up to -1.4 nA at -60 mV; reversal at approximatety 0 mV). The currents exhibited a patchy distribution along the axon and dendrites. In current-clamp recordings, repetitive firing driven by somatic current injection was blocked by uncaging GABA on the secondary dendrite approximately 140 microm from the soma, and the blocking distance decreased with increasing current. In the secondary dendrites, backpropagated action potentials were measured 93-152 microm from the soma, where they were attenuated by a factor of 0.75 +/- 0.07 (mean +/- SD) and slightly broadened (1.19 +/- 0.10), independent of activity (35-107 Hz). Uncaging GABA on the distal dendrite had little effect on somatic spikes but attenuated backpropagating action potentials by a factor of 0.68 +/- 0.15 (0.45-0.60 microJ flash with 1-mM caged GABA); attenuation was localized to a zone of width 16.3 +/- 4.2 microm around the point of GABA release. These results reveal the contrasting actions of inhibition at different locations along the dendrite: proximal inhibition blocks firing by shunting somatic current, whereas distal inhibition can impose spatial patterns of dendrodendritic transmission by locally attenuating backpropagating action potentials. The secondary dendrites are designed with a high safety factor for backpropagation, to facilitate reliable transmission of the outgoing spike-coded data stream, in parallel with the integration of inhibitory inputs.

Protein Kinase Modulation of Dendritic K+ Channels in Hippocampus Involves a Mitogen-Activated Protein Kinase Pathway

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+ channels in CA1 pyramidal neurons in the hippocampus. We show here that both of these signaling pathways converge on extracellular-regulated kinases (ERK)-specific MAPK in mediating this reduction in dendritic K+ current, which is confirmed, in parallel, by biochemical assays using phosphospecific antibodies against the ppERK and pKv4.2. Furthermore, immunostaining indicates dendritic localization of ppERK and pKv4.2. Taken together, these results demonstrate that dendritic, A-type K+ channels are dually regulated by PKA and PKC through a common downstream pathway involving MAPK, and the modulation of these K+ channels may be accounted for by the phosphorylation of Kv4.2 subunits.

Dendritic K+ channels contribute to spike-timing dependent long-term potentiation in hippocampal pyramidal neurons.

We investigated the role of A-type K(+) channels for the induction of long-term potentiation (LTP) of Schaffer collateral inputs to hippocampal CA1 pyramidal neurons. When low-amplitude excitatory postsynaptic potentials (EPSPs) were paired with two postsynaptic action potentials in a theta-burst pattern, N-methyl-d-aspartate (NMDA)-receptor-dependent LTP was induced. The amplitudes of the back-propagating action potentials were boosted in the dendrites only when they were coincident with the EPSPs. Mitogen-activated protein kinase (MAPK) inhibitors PD 098059 or U0126 shifted the activation of dendritic K(+) channels to more hyperpolarized potentials, reduced the boosting of dendritic action potentials by EPSPs, and suppressed the induction of LTP. These results support the hypothesis that dendritic K(+) channels and the boosting of back-propagating action potentials contribute to the induction of LTP in CA1 neurons.

Novel dynamics of dendritic integration in the high conductance state of cortical neurons

Neocortical neurons in vivo operate in a high-conductance state which may affect the dynamics of dendritic integration, but this aspect remains only barely characterized. We investigated this problem by using biophysical models of morphologically reconstructed neocortical pyramidal neurons in which isolated and paired synaptic events were studied according to their dendritic location. We show that during active states, there is an ongoing dynamics of randomly occurring forward- and back-propagating dendritic action potentials. This dynamics determinantly impacts on how individual or paired synaptic events interact, leading to a type of integrative behavior which is different from classical models of dendritic integration.

Ghostbursting: a novel neuronal burst mechanism.

Pyramidal cells in the electrosensory lateral line lobe (ELL) of weakly electric fish have been observed to produce high-frequency burst discharge with constant depolarizing current (Turner et al., 1994). We present a two-compartment model of an ELL pyramidal cell that produces burst discharges similar to those seen in experiments. The burst mechanism involves a slowly changing interaction between the somatic and dendritic action potentials. Burst termination occurs when the trajectory of the system is reinjected in phase space near the "ghost" of a saddle-node bifurcation of fixed points. The burst trajectory reinjection is studied using quasi-static bifurcation theory, that shows a period doubling transition in the fast subsystem as the cause of burst termination. As the applied depolarization is increased, the model exhibits first resting, then tonic firing, and finally chaotic bursting behavior, in contrast with many other burst models. The transition between tonic firing and burst firing is due to a saddle-node bifurcation of limit cycles. Analysis of this bifurcation shows that the route to chaos in these neurons is type I intermittency, and we present experimental analysis of ELL pyramidal cell burst trains that support this model prediction. By varying parameters in a way that changes the positions of both saddle-node bifurcations in parameter space, we produce a wide gallery of burst patterns, which span a significant range of burst time scales.

The other half of Hebb: K+ channels and the regulation of neuronal excitability in the hippocampus.

Historically, much attention has focused on the mechanisms of activity-dependent plasticity since the description of long-term potentiation by Bliss and Lomo in the early 1970s, while extrasynaptic changes have received much less interest. However, recent work has concentrated on the role of back-propagating action potentials in hippocampal dendrites in synaptic plasticity. In this review, we focus on the modulation of back-propagating action potentials by K+ currents in the dendrites of hippocampal cells. We described the primary K+-channel subunits and their interacting subunits that most likely contribute to these currents, and how these sites can be regulated by phosphorylation and other mechanisms. In conclusion, we provide a model for an alternative form of coincidence detection through K+ channels in the hippocampus.

Activity-dependent accumulation of Ca2+ in axon and dendrites of the leech Leydig neuron.

We have investigated Ca2+ changes evoked by single action potentials (APs) in axon and dendrites of leech Leydig neurons. Dendritic Ca2+ transients induced by an AP were twice as large as in the axon, and Ca2+ recovery was significantly faster in the dendrites as compared to the axon. The AP-induced Ca2+ transients were blocked by Co2+ and suppressed in Ca2+-free saline, indicating Ca2+ influx through voltage-activated channels. During a train of APs, Ca2+ accumulated significantly more in the axon than in the dendrites. Suppression of the Ca2+ influx changed the shape of the action potential and increased the firing frequency. The results suggest a functional role of Ca2+ influx and Ca2+ accumulation during electrical activity in different neuronal subcompartments.

Coincident Spiking Activity Induces Long-Term Changes in Inhibition of Neocortical Pyramidal Cells

In pyramidal cells, induction of long-term potentiation (LTP) and long-term depression (LTD) of excitatory synaptic transmission by coincidence of presynaptic and postsynaptic activity is considered relevant to learning processes in vivo. Here we show that temporally correlated spiking activity of a pyramidal cell and an inhibiting interneuron may cause LTD or LTP of unitary IPSPs. Polarity of change in synaptic efficacy depends on timing between Ca(2+) influx induced by a backpropagating train of action potentials (APs) in pyramidal cell dendrites (10 APs, 50 Hz) and subsequent activation of inhibitory synapses. LTD of IPSPs was induced by synaptic activation in the vicinity of the AP train (<300 msec relative to the beginning of the train), whereas LTP of IPSPs was initiated with more remote synaptic activation (>400 msec relative to the beginning of the AP train). Solely AP trains induced neither LTP nor LTD. Both LTP and LTD were prevented by 5 mm BAPTA loaded into pyramidal cells. LTD was prevented by 5 mm EGTA, whereas EGTA failed to affect LTP. Synaptic plasticity was not dependent on activation of GABA(B) receptors. It was also not affected by the antagonists of vesicular exocytosis, botulinum toxin D, and GDP-beta-S.

Back-propagating action potentials mediate calcium signalling in dendrites of bitufted interneurons in layer 2/3 of rat somatosensory cortex.

1. Bitufted interneurons in layer 2/3 of the rat (P14) somatosensory cortex have elongated apical and basal dendritic arbors that can span the entire depth of the cortex. Simultaneous dendritic and somatic whole-cell voltage recordings combined with Ca2+ fluorescence measurements were made to quantify voltage and Ca2+ signalling in dendritic arbors of bitufted neurons. 2. Action potentials (APs) initiated close to the soma by brief current injection back-propagated into the apical and basal dendritic arbors and evoked a transient increase in volume-averaged dendritic Ca2+ concentration (Delta[Ca(2+)](i)) of about 140 nM peak amplitude per AP. The AP evoked Ca2+ signal decayed with a time constant of about 200 ms. 3. A relatively high endogenous Ca(2+) binding ratio of approximately 285 determines the comparatively small rise in [Ca(2+)](i) of bitufted cell dendrites evoked by a back-propagating AP. 4. The [Ca(2+)](i) transient evoked by back-propagating dendritic APs decreased with distance (< or = 50 microm) from the soma in some neurons. At distances greater than 50 microm transients did not show a spatial gradient between the proximal and distal dendritic branches. 5. During trains of APs the mean amplitude of the steady-state increase in dendritic [Ca(2+)](i) encoded the AP frequency linearly up to 40 Hz with a slope of 20 nM Hz(-1). 6. The results suggest that APs initiated in the axon of bitufted neurons back-propagate and 'copy' the pattern of the axon's electrical activity also to the dendritic arbor. The AP pattern is transduced into a transient rise of dendritic [Ca(2+)](i) which, presumably, can regulate the receptive properties of the dendritic arbor for synaptic input. 7. Bitufted interneurons in layer 2/3 of the rat (P14) somatosensory cortex have elongated apical and basal dendritic arbors that can span the entire depth of the cortex. Simultaneous dendritic and somatic whole-cell voltage recordings combined with Ca2+ fluorescence measurements were made to quantify voltage and Ca2+ signalling in dendritic arbors of bitufted neurons. 8. Action potentials (APs) initiated close to the soma by brief current injection back-propagated into the apical and basal dendritic arbors and evoked a transient increase in volume-averaged dendritic Ca2+ concentration (Delta[Ca(2+)](i)) of about 140 nM peak amplitude per AP. The AP evoked Ca2+ signal decayed with a time constant of about 200 ms. 9. A relatively high endogenous Ca2+ binding ratio of approximately 285 determines the comparatively small rise in [Ca(2+)](i) of bitufted cell dendrites evoked by a back-propagating AP. 10. The [Ca(2+)](i) transient evoked by back-propagating dendritic APs decreased with distance (< or = 50 microm) from the soma in some neurons. At distances greater than 50 microm transients did not show a spatial gradient between the proximal and distal dendritic branches. 11. During trains of APs the mean amplitude of the steady-state increase in dendritic [Ca(2+)](i) encoded the AP frequency linearly up to 40 Hz with a slope of 20 nM Hz(-1). 12. The results suggest that APs initiated in the axon of bitufted neurons back-propagate and also 'copy' the pattern of the axon's electrical activity to the dendritic arbor. The AP pattern is transduced into a transient rise of dendritic [Ca(2+)](i) which, presumably, can regulate the receptive properties of the dendritic arbor for synaptic input.

Dendritic mechanisms underlying the coupling of the dendritic with the axonal action potential initiation zone of adult rat layer 5 pyramidal neurons.

1. Double, triple and quadruple whole-cell voltage recordings were made simultaneously from different parts of the apical dendritic arbor and the soma of adult layer 5 (L5) pyramidal neurons. We investigated the membrane mechanisms that support the conduction of dendritic action potentials (APs) between the dendritic and axonal AP initiation zones and their influence on the subsequent AP pattern. 2. The duration of the current injection to the distal dendritic initiation zone controlled the degree of coupling with the axonal initiation zone and the AP pattern. 3. Two components of the distally evoked regenerative potential were pharmacologically distinguished: a rapidly rising peak potential that was TTX sensitive and a slowly rising plateau-like potential that was Cd(2+) and Ni(2+) sensitive and present only with longer-duration current injection. 4. The amplitude of the faster forward-propagating Na(+)-dependent component and the amplitude of the back-propagating AP fell into two classes (more distinctly in the forward-propagating case). Current injection into the dendrite altered propagation in both directions. 5. Somatic current injections that elicited single Na(+) APs evoked bursts of Na(+) APs when current was injected simultaneously into the proximal apical dendrite. The mechanism did not depend on dendritic Na(+)-Ca(2+) APs. 6. A three-compartment model of a L5 pyramidal neuron is proposed. It comprises the distal dendritic and axonal AP initiation zones and the proximal apical dendrite. Each compartment contributes to the initiation and to the pattern of AP discharge in a distinct manner. Input to the three main dendritic arbors (tuft dendrites, apical oblique dendrites and basal dendrites) has a dominant influence on only one of these compartments. Thus, the AP pattern of L5 pyramids reflects the laminar distribution of synaptic activity in a cortical column.

Synaptic background activity affects the dynamics of dendritic integration in model neocortical pyramidal neurons

Neocortical pyramidal neurons in vivo are subject to an intense synaptic background activity which may significantly impact on dendritic integration, but this aspect is largely unexplored. Here we use computational models of morphologically-reconstructed pyramidal neurons, in which synaptic background activity was simulated according to recent measurements in cat parietal cortex. We show that background activity markedly enhances voltage attenuation, which results in a relative electrotonic “isolation” of different dendritic segments. On the other hand, the active propagation of action potentials in dendrites is minimally affected. The consequence is that inputs are integrated locally and their impact on the soma is independent on their position in the dendritic tree. We conclude that background activity sets up a dynamics of dendritic integration which is radically different compared to quiescent states.

Subthreshold inactivation of Na+ and K+ channels supports activity-dependent enhancement of back-propagating action potentials in hippocampal CA1.

Back-propagating action potentials in CA1 pyramidal neurons may provide the postsynaptic dendritic depolarization necessary for the induction of long-term synaptic plasticity. The amplitudes of back-propagating action potentials are not all or none but are limited in amplitude by dendritic A-type K+ channels. Previous studies of back-propagating action potentials have suggested that prior depolarization of the dendritic membrane reduces A-type channel availability through inactivation, resulting in an enhanced, or boosted, dendritic action potential. However, inactivation kinetics in the subthreshold potential range have not been directly measured. Furthermore, the corresponding rates of Na+ channel inactivation with depolarization have not been considered. Here we report in cell-attached patches (150-220 microm from the soma, 32 degrees C) that at 20-mV positive to rest, A-type K+ channels inactivated with a single exponential time constant of 6 ms, whereas Na+ channels inactivated with a time constant of 37 ms. The ratio of available Na+ to K+ current increased as the duration of the depolarization increased. Thus the subthreshold properties of Na+ and A-type K+ channels provide a mechanism by which information about the level of synaptic activity may be encoded in the amplitude of back-propagating action potentials.

Mechanisms of Generation of Pacemaker Activity by Identified Helix Neurons

We studied the mechanisms of generation of pacemaker activity in identified neurons of Helix pomatia. For this purpose, we isolated the PPa2 and PPa7 neurons generating spontaneous rhythmic monomodal activity and PPa1 neuron with bursting activity. It was demonstrated that isolated PPa2 and PPa7 cells produce endogenous rhythmic activity that was not considerably modified by external application of 1 mM CdCl2. Sometimes, only low-amplitude dendritic action potentials (AP) were observed instead of generation of full-amplitude somatic AP. In contrast, isolation of the PPa1 neuron eliminated its bursting activity, but subsequent application of oxytocin on this neuron recovered such activity. This finding shows that the bursting activity of the PPa1 neuron is of an exogenous nature. Application of 1 mM CdCl2 suppressed this bursting activity, but when Cd2+ was applied against the background of superfusion of the neuron with Ringer solution containing a bursting activity-initiating neuropeptide obtained from the molluscan CNS, this blocker was incapable of suppressing the bursting activity. A blocker of the hyperpolarization-activated current (Ih, H current), Cs+ (10 mM) exerted no noticeable effect on the activity of the studied neurons. Our findings allow us to conclude that the pacemaker activity is initiated within the dendritic tree of a cell and is then electrotonically spread to the soma, where full-amplitude AP are generated. It seems probable that Ca2+ ions and H current are not directly involved in generation of the pacemaker activity in the studied snail neurons.

Analysis of calcium channels in single spines using optical fluctuation analysis.

Most synapses form on small, specialized postsynaptic structures known as dendritic spines. The influx of Ca2+ ions into such spines--through synaptic receptors and voltage-sensitive Ca2+ channels (VSCCs)--triggers diverse processes that underlie synaptic plasticity. Using two-photon laser scanning microscopy, we imaged action-potential-induced transient changes in Ca2+ concentration in spines and dendrites of CA1 pyramidal neurons in rat hippocampal slices. Through analysis of the large trial-to-trial fluctuations in these transients, we have determined the number and properties of VSCCs in single spines. Here we report that each spine contains 1-20 VSCCs, and that this number increases with spine volume. We are able to detect the opening of a single VSCC on a spine. In spines located on the proximal dendritic tree, VSCCs normally open with high probability (approximately 0.5) following dendritic action potentials. Activation of GABA(B) receptors reduced this probability in apical spines to approximately 0.3 but had no effect on VSCCs in dendrites or basal spines. Our studies show that the spatial distribution of VSCC subtypes and their modulatory potential is regulated with submicrometre precision.

Dendro-somatic distribution of calcium-mediated electrogenesis in purkinje cells from rat cerebellar slice cultures.

The role of Ca2+ entry in determining the electrical properties of cerebellar Purkinje cell (PC) dendrites and somata was investigated in cerebellar slice cultures. Immunohistofluorescence demonstrated the presence of at least three distinct types of Ca2+ channel proteins in PCs: the alpha1A subunit (P/Q type Ca2+ channel), the alpha1G subunit (T type) and the alpha1E subunit (R type). In PC dendrites, the response started in 66 % of cases with a slow depolarization (50 +/- 15 ms) triggering one or two fast (approximately 1 ms) action potentials (APs). The slow depolarization was identified as a low-threshold non-P/Q Ca2+ AP initiated, most probably, in the dendrites. In 16 % of cases, this response propagated to the soma to elicit an initial burst of fast APs. Somatic recordings revealed three modes of discharge. In mode 1, PCs display a single or a short burst of fast APs. In contrast, PCs fire repetitively in mode 2 and 3, with a sustained discharge of APs in mode 2, and bursts of APs in mode 3. Removal of external Ca2+ or bath applications of a membrane-permeable Ca2+ chelator abolished repetitive firing. Tetraethylammonium (TEA) prolonged dendritic and somatic fast APs by a depolarizing plateau sensitive to Cd2+ and to omega-conotoxin MVII C or omega-agatoxin TK. Therefore, the role of Ca2+ channels in determining somatic PC firing has been investigated. Cd2+ or P/Q type Ca2+ channel-specific toxins reduced the duration of the discharge and occasionallyinduced the appearance of oscillations in the membrane potential associated with bursts of APs. In summary, we demonstrate that Ca2+ entry through low-voltage gated Ca2+ channels, not yet identified, underlies a dendritic AP rarelyeliciting a somatic burst of APs whereas Ca2+ entry through P/Q type Ca2+ channels allowed a repetitive firing mainly by inducing a Ca2+-dependent hyperpolarization.

Transcription-dependent neuronal plasticity: The nuclear calcium hypothesis.

In neurons, calcium ions control gene transcription induced by synaptic activity. The states and histories of neuronal activity are represented by a calcium code that comprises the site of calcium entry, and the amplitude, duration and spatial properties of signal-evoked calcium transients. The calcium code is used to transform specific firing patterns into qualitatively and quantitatively distinct transcriptional responses. The following hypothesis is proposed: electrical activity causes long-lasting, transcription-dependent changes in neuronal functions when synaptically evoked calcium transients associated with the stimulation propagate to the nucleus; gene transcription activated by dendritic calcium signals only is insufficient to consolidate functional alterations long-term. Similar to enduring increases in synaptic efficacy, nuclear calcium transients are induced by high-frequency firing patterns or by weak synaptic inputs coinciding with backpropagating dendritic action potentials. Nuclear calcium stimulates CREB-mediated transcription and, through inducing the activity of the transcriptional coactivator CREB-binding protein (CBP), may modulate the expression of numerous genes including neurotransmitter receptors and scaffolding proteins. Increases in the transcription rate of target genes are predicted to be transient and in many cases small, however, they collectively contribute to the maintenance of changes in synaptic efficacy. Nuclear calcium may be the common regulator of diverse transcription-dependent forms of neuronal plasticity.