Implementing Dynamic Clamp with Synaptic and Artificial Conductances in Mouse Retinal Ganglion Cells

Ganglion cells are the output neurons of the retina and their activity reflects the integration of multiple synaptic inputs arising from specific neural circuits. Patch clamp techniques, in voltage clamp and current clamp configurations, are commonly used to study the physiological properties of neurons and to characterize their synaptic inputs. Although the application of these techniques is highly informative, they pose various limitations. For example, it is difficult to quantify how the precise interactions of excitatory and inhibitory inputs determine response output. To address this issue, we used a modified current clamp technique, dynamic clamp, also called conductance clamp ^{1, 2, 3} and examined the impact of excitatory and inhibitory synaptic inputs on neuronal excitability. This technique requires the injection of current into the cell and is dependent on the real-time feedback of its membrane potential at that time. The injected current is calculated from predetermined excitatory and inhibitory synaptic conductances, their reversal potentials and the cell''s instantaneous membrane potential. Details on the experimental procedures, patch clamping cells to achieve a whole-cell configuration and employment of the dynamic clamp technique are illustrated in this video article. Here, we show the responses of mouse retinal ganglion cells to various conductance waveforms obtained from physiological experiments in control conditions or in the presence of drugs. Furthermore, we show the use of artificial excitatory and inhibitory conductances generated using alpha functions to investigate the responses of the cells.     

Dynamic modification of dendritic cable properties and synaptic transmission by voltage-gated potassium channels

Computer simulations of a dendrite possessing voltage-sensitive potassium conductances were used to determine the effects of these conductances on synaptic transmission and on the propagation of synaptic signals within the dendritic tree. Potassium conductances had two principal effects on voltage transients generated by current injections or synaptic conductances. Locally (near the source of the transient), voltage-gated potassium channels produced a potassium shunt current that reduced the amplitude of voltage transients generated by depolarizing currents. This shunt current increased as the amplitude of the depolarizing transient increased and so acted to prevent large synaptic transients from reaching levels that would saturate due to a reduction in driving force. In the presence of rapidly activating potassium currents, excitatory synapses produced larger synaptic currents that were more linearly related to synaptic conductance, but these produced smaller voltage transients. The maximum amplitudes of the voltage transients were limited by the voltage sensitivity of the K⁺ conductance and the rate at which it could activate. Sufficiently rapid synaptic currents could outrun the K⁺ conductance and thus achieve high local peak amplitudes. These effects of K⁺ conductances were unrelated to whether they were located on dendrites or not, being related only to their proximity to the source of synaptic current. The second class of effects of K⁺ conductances depended on their alteration of the electrotonic structure of the postsynaptic cell and so were observed only when they were located on postsynaptic dendrites. Voltage-gated K⁺ conductances produced voltage-dependent electrotonic expansion of depolarized dendrites, which had the effect of isolating synaptic inputs on depolarized dendrites from events on the rest of the neuron. Thus, synapses on the same dendrite interacted destructively to a degree much greater than that expected from the classical driving force nonlinearity. Synapses located proximally to a depolarized dendritic region were less effected than those located distally, and the range of the nonlinear interaction between synapses was dependent on the kinetics of activation and deactivation of the conductance. When present in conjunction with rapidly activating dendritic sodium conductance, the potassium conductance sharpened the requirement for spatial and temporal coincidence to produce synaptic boosting by inward currents, and suppressed out-of-synchrony synaptic inputs.     

Transfer properties of neuronal dendrites with tonically activated conductances

The somatopetal current transfer was studied in the mathematical models of a reconstructed brainstem motoneuron with tonically activated excitatory synaptic inputs uniformly distributed over dendritic arborization. The soma and axon provided a constant passive leak. The extrasynaptic dendritic membrane was either passive or active (of a Hodgkin-Huxley type). The longitudinal membrane current density (per unit path length) was used as an estimate of the current transfer effectiveness of different dendritic paths. Introduction of a steady uniform voltage-independent conductance per unit membrane area simulated such a synaptic activation. This actions always produced a spatially inhomogeneous membrane depolarization decaying from the distal dendritic tips toward the soma. The reason for such an inhomogeneity was the preponderance of somatopetal over somatofugal input conductance at every site in the dendrites with sealed distal ends and a leaky somatic end. In active dendrites, partial voltage-dependent extrasynaptic conductances followed this depolarization according to their activation-inactivation kinetics. The greater the local depolarization, the greater the contribution of the non-inactivating potassium conductance to the total membrane conductance. The contribution of the inactivated sodium conductance was one order of magnitude smaller. Correspondingly, the effective equilibrium potential of the total transmembrane current became spatially inhomogeneous and shifted to the potassium equilibrium potential. In the passive dendrites, the equilibrium potential remained spatially homogeneous. Inhomogeneities of the dendritic geometry (abrupt change in the diameter and, especially, asymmetrical branching) caused characteristic perturbations in the voltage gradient, so that the path profiles of the voltage, conductances, and currents diverged. This indicated a geometry-induced separation of the dendritic paths in their transfer effectiveness. Active dendrites of the same geometry were less effective than passive ones due to the effect of the potassium conductance associated with the hyperpolarizing equilibrium potential.     

Voltage-imaging and simulation of effects of voltage- and agonist-activated conductances on soma-dendritic voltage coupling in cerebellar Purkinje cells

We investigated the spread of membrane voltage changes from the soma into the dendrites of cerebellar Purkinje cells by using voltage-imaging techniques in combination with intracellular recordings and by performing computer simulations using a detailed compartmental model of a cerebellar Purkinje cell. Fluorescence signals from single Purkinje cells in cerebellar cultures stained with the styryl dye di-4-ANEPPS were detected with a 10 × 10 photodiode array and a charge coupled device (CCD). Fluorescence intensity decreased and increased with membrane depolarization and hyperpolarization, respectively. The relation between fractional fluorescence change (F/F) and membrane potential could be described by a linear function with a slope of up to – 3%/100 mV. Hyperpolarizing and depolarizing voltage jumps applied to Purkinje cells voltage-clamped with an intrasomatic recording electrode induced dendritic dye signals, demonstrating that these voltage transients invaded the dendrites. Dye signals induced by depolarizing somatic voltage jumps were weaker in the dendrites, when compared with those induced by hyperpolarizing voltage jumps. Dendritic responses to hyperpolarizing voltage steps applied at the soma were attenuated when membrane conductance was increased by muscimol, an agonist for GABA_Areceptors.Corresponding experimental protocols were applied to a previously developed detailed compartmental model of a Purkinje cell. In the model, as in the electrophysiological recordings, voltage attenuation from soma to dendrites increased under conditions where membrane conductance is increased by depolarization or by activation of GABA_A receptors, respectively.We discuss how these results affect voltage clamp studies of synaptic currents and synaptic integration in Purkinje cells.     

Solutions for transients in arbitrarily branching cables: III. Voltage clamp problems.

Branched cable voltage recording and voltage clamp analytical solutions derived in two previous papers are used to explore practical issues concerning voltage clamp. Single exponentials can be fitted reasonably well to the decay phase of clamped synaptic currents, although they contain many underlying components. The effective time constant depends on the fit interval. The smoothing effects on synaptic clamp currents of dendritic cables and series resistance are explored with a single cylinder + soma model, for inputs with different time courses. "Soma" and "cable" charging currents cannot be separated easily when the soma is much smaller than the dendrites. Subtractive soma capacitance compensation and series resistance compensation are discussed. In a hippocampal CA1 pyramidal neurone model, voltage control at most dendritic sites is extremely poor. Parameter dependencies are illustrated. The effects of series resistance compound those of dendritic cables and depend on the "effective capacitance" of the cell. Plausible combinations of parameters can cause order-of-magnitude distortions to clamp current waveform measures of simulated Schaeffer collateral inputs. These voltage clamp problems are unlikely to be solved by the use of switch clamp methods.     

Geometry-induced features of current transfer in neuronal dendrites with tonically activated conductances

The impact of dendritic geometry on somatopetal transfer of the current generated by steady uniform activation of excitatory synaptic conductance distributed over passive, or active (Hodgkin-Huxley type), dendrites was studied in simulated neurons. Such tonic activation was delivered to the uniform dendrite and to the dendrites with symmetric or asymmetric branching with various ratios of branch diameters. Transfer effectiveness of the dendrites with distributed sources was estimated by the core current increment directly related to the total membrane current per unit path length. The effectiveness decreased with increasing path distance from the soma along uniform branches. The primary reason for this was the asymmetry of somatopetal vs somatofugal input core conductance met by synaptic current due to a greater leak conductance at the proximal end of the dendrite. Under these conditions, an increasing somatopetal core current and a corresponding drop of the depolarization membrane potential occurred. The voltage-dependent extrasynaptic conductances, if present, followed this depolarization. Consequently, the driving potential and membrane current densities decreased with increasing path distance from the soma. All path profiles were perturbed at bifurcations, being identical in symmetrical branches and diverging in asymmetrical ones. These perturbations were caused by voltage gradient breaks (abrupt change in the profile slope) occurring at the branching node due to coincident inhomogeneity of the dendritic core cross-section area and its conductance. The gradient was greater on the side of the smaller effective cross-section. Correspondingly, the path profiles of the somatopetal current transfer effectiveness were broken and/or diverged. The dendrites, their paths, and sites which were more effective in the current transfer from distributed sources were also more effective in the transfer from single-site inputs. The effectiveness of the active dendrite depended on the activation-inactivation kinetics of its voltage-gated conductances. In particular, dendrites with the same geometry were less effective with the Hodgkin-Huxley membrane than with the passive membrane, because of the effect of the noninactivating K⁺-conductance associated with the hyperpolarization equilibrium potential. Such electrogeometrical coupling may form a basis for path-dependent input-output conversion in the dendritic neurons, as the output discharge rate is defined by the net current delivered to the soma. Received: 18 December 1997 / Accepted in revised form: 12 June 1998     

Evidence for low GluR2 AMPA receptor subunit expression at synapses in the rat basolateral amygdala

Fast excitatory synaptic responses in basolateral amygdala (BLA) neurons are mainly mediated by ionotropic glutamate receptors of the alpha-amino-3-hydroxy-5-methylisoxazole-4-propionate (AMPA) subtype. AMPA receptors containing an edited GluR2 subunit are calcium impermeable, whereas those that lack this subunit are calcium permeable and also inwardly rectifying. Here, we sought to determine the extent to which synapses in the rat BLA have AMPA receptors with GluR2 subunits. We assessed GluR2 protein expression in the BLA by immunocytochemistry with a GluR2 subunit-specific antiserum at the light and electron microscopic level; for comparison, a parallel examination was carried out in the hippocampus. We also recorded from amygdala brain slices to examine the voltage-dependent properties of AMPA receptor- mediated evoked synaptic currents in BLA principal neurons. At the light microscopic level, GluR2 immunoreactivity was localized to the perikarya and proximal dendrites of BLA neurons; dense labeling was also present over the pyramidal cell layer of hippocampal subfields CA1 and CA3. In electron micrographs from the BLA, most of the synapses were asymmetrical with pronounced postsynaptic densities (PSD). They contained clear, spherical vesicles apposed to the PSD and were predominantly onto spines (86%), indicating that they are mainly with BLA principal neurons. Only 11% of morphological synapses in the BLA were onto postsynaptic elements that showed GluR2 immunoreactivity, in contrast to hippocampal subfields CA1 and CA3 in which 76% and 71% of postsynaptic elements were labeled (p < 0.001). Synaptic staining in the BLA and hippocampus, when it occurred, was exclusively postsynaptic, and particularly heavy over the PSD. In whole-cell voltage clamp recordings, 72% of BLA principal neurons exhibited AMPA receptor-mediated synaptic currents evoked by external capsule stimulation that were inwardly rectifying. Although BLA principal neurons express perikaryal and proximal dendritic GluR2 immunoreactivity, few synapses onto these neurons express GluR2, and a preponderance of principal neurons have inwardly rectifying AMPA-mediated synaptic currents, suggesting that targeting of GluR2 to synapses is restricted. Many BLA synaptic AMPA receptors are likely to be calcium permeable and could play roles in synaptic plasticity, epileptogenesis and excitoxicity.     

Non-Decaying postsynaptics potentials and delayed spikes in hippocampal pyramidal neurons generated by a zero slope conductance created by the persistent Na+ current

The negative slope conductance created by the persistent sodium current (I_NaP) prolongs the decay phase of excitatory postsynaptic potentials (EPSPs). In a recent study, we demonstrated that this effect was due to an increase of the membrane time constant. When the negative slope conductance opposes completely the positive slope conductances of the other currents it creates a zero slope conductance region. In this region the membrane time constant is infinite and the decay phase of the EPSPs is virtually absent. Here we show that non-decaying EPSPs are present in CA1 hippocampal pyramidal cells in the zero slope conductance region, in the suprathreshold range of membrane potential. Na⁺ channel block with tetrodotoxin abolishes the non-decaying EPSPs. Interestingly, the non-decaying EPSPs are observed only in response to artificial excitatory postsynaptic currents (aEPSCs) of small amplitude, and not in response to aEPSCs of big amplitude. We also observed concomitantly delayed spikes with long latencies and high variability only in response to small amplitude aEPSCs. Our results showed that in CA1 pyramidal neurons I_NaP creates non-decaying EPSPs and delayed spikes in the subthreshold range of membrane potentials, which could potentiate synaptic integration of synaptic potentials coming from distal regions of the dendritic tree.     

Effects of active conductance distribution over dendrites on the synaptic integration in an identified nonspiking interneuron

The synaptic integration in individual central neuron is critically affected by how active conductances are distributed over dendrites. It has been well known that the dendrites of central neurons are richly endowed with voltage- and ligand-regulated ion conductances. Nonspiking interneurons (NSIs), almost exclusively characteristic to arthropod central nervous systems, do not generate action potentials and hence lack voltage-regulated sodium channels, yet having a variety of voltage-regulated potassium conductances on their dendritic membrane including the one similar to the delayed-rectifier type potassium conductance. It remains unknown, however, how the active conductances are distributed over dendrites and how the synaptic integration is affected by those conductances in NSIs and other invertebrate neurons where the cell body is not included in the signal pathway from input synapses to output sites. In the present study, we quantitatively investigated the functional significance of active conductance distribution pattern in the spatio-temporal spread of synaptic potentials over dendrites of an identified NSI in the crayfish central nervous system by computer simulation. We systematically changed the distribution pattern of active conductances in the neuron's multicompartment model and examined how the synaptic potential waveform was affected by each distribution pattern. It was revealed that specific patterns of nonuniform distribution of potassium conductances were consistent, while other patterns were not, with the waveform of compound synaptic potentials recorded physiologically in the major input-output pathway of the cell, suggesting that the possibility of nonuniform distribution of potassium conductances over the dendrite cannot be excluded as well as the possibility of uniform distribution. Local synaptic circuits involving input and output synapses on the same branch or on the same side were found to be potentially affected under the condition of nonuniform distribution while operation of the major input-output pathway from the soma side to the one on the opposite side remained the same under both conditions of uniform and nonuniform distribution of potassium conductances over the NSI dendrite.     

可视膜片钳法记录初级传入纤维介导的脊髓背角神经元突触后电流

本文描述了用明胶半包埋法制备带背根脊髓薄片的实验步骤,和在脊髓背角记录由初级传入纤维介导的突触后电流的可视膜片钳法。手术制备一段带背根的脊髓标本,并用20％的明胶包埋在琼脂块上,再用振动切片机切片获得带背根的脊髓薄片。通过红外线可视的引导,在脊髓背角神经元上建立全细胞封接模式。在钳制电压为-70mV条件下,记录自发的和背根刺激引起的兴奋性突触后电流。以传入纤维的传导速度与刺激阈值为指标,可以区分A样纤维与C样纤维兴奋性突触后电流。在钳制电压为0mV条件下,记录自发的和背根刺激引起的抑制性突触后电流。用5μmol／L的士宁或20μmol／L的荷包牡丹碱分离出γ-氨基丁酸能或甘氨酸能的抑制性突触后电流。用可视膜片钳方法可以准确测量脊髓背角神经元的突触后电流,从而研究初级传入突触的传递过程。更重要的是,在红外线可视观察的帮助下,建立膜片钳封接的成功率显著提高,同时也使记录研究脊髓背角深层神经元变得更加容易。本研究为探索初级传入突触传递过程提供了一个有效的方法。     

Nonstationary fluctuation analysis and direct resolution of single channel currents at postsynaptic sites.

In order to measure unitary properties of receptor channels at the postsynaptic site, the noise within the decay phases of inhibitory postsynaptic currents (IPSCs) and of N-methyl-D-aspartate (NMDA)-dependent excitatory postsynaptic currents (EPSCs) in rat hippocampal neurons was studied by nonstationary fluctuation analysis. Least squares scaling of the mean current was used to circumvent the wide variation in amplitude of postsynaptic currents. The variance of fluctuations around the expected current was analyzed to calculate single channel conductance, and fluctuation kinetics were studied with power spectra. The single channel conductance underlying the IPSC was measured as 14 pS, whereas that underlying the EPSC was 42 pS. Openings of the EPSC channel could also be resolved directly in low-noise whole-cell recordings, allowing verification of the accuracy of the fluctuation analysis. The results are the first measurements of the properties of single postsynaptic channels activated during synaptic currents, and suggest that the technique can be widely applicable in investigations of synaptic mechanism and plasticity.     

Determinants of synaptic integration and heterogeneity in rebound firing explored with data-driven models of deep cerebellar nucleus cells

Significant inroads have been made to understand cerebellar cortical processing but neural coding at the output stage of the cerebellum in the deep cerebellar nuclei (DCN) remains poorly understood. The DCN are unlikely to just present a relay nucleus because Purkinje cell inhibition has to be turned into an excitatory output signal, and DCN neurons exhibit complex intrinsic properties. In particular, DCN neurons exhibit a range of rebound spiking properties following hyperpolarizing current injection, raising the question how this could contribute to signal processing in behaving animals. Computer modeling presents an ideal tool to investigate how intrinsic voltage-gated conductances in DCN neurons could generate the heterogeneous firing behavior observed, and what input conditions could result in rebound responses. To enable such an investigation we built a compartmental DCN neuron model with a full dendritic morphology and appropriate active conductances. We generated a good match of our simulations with DCN current clamp data we recorded in acute slices, including the heterogeneity in the rebound responses. We then examined how inhibitory and excitatory synaptic input interacted with these intrinsic conductances to control DCN firing. We found that the output spiking of the model reflected the ongoing balance of excitatory and inhibitory input rates and that changing the level of inhibition performed an additive operation. Rebound firing following strong Purkinje cell input bursts was also possible, but only if the chloride reversal potential was more negative than −70 mV to allow de-inactivation of rebound currents. Fast rebound bursts due to T-type calcium current and slow rebounds due to persistent sodium current could be differentially regulated by synaptic input, and the pattern of these rebounds was further influenced by HCN current. Our findings suggest that active properties of DCN neurons could play a crucial role for signal processing in the cerebellum.     

Influence of the Geometry of an Axo-Dendritic Synapse and Its Position on the Dendrite on the Current Recorded from the Neuronal Soma

Using mathematical simulation,we studied the influence of the geometry of an axo-dendritic synapse and its position on the dendrite on the value of the postsynaptic current that arrives at the soma. It was shown that the geometric dimensions of the synaptic cleft and the conductance of postsynaptic receptor-channel complexes determine the value of the current coming into the postsynaptic cell, while the geometry and conductance of the dendrite determine the part of this current arriving at the soma. At a constant conductance of the postsynaptic membrane but with an increase in the diameter of the synaptic contact and a decrease in the width of the synaptic cleft, the current coming into the postsynaptic unit decreases, but the reversal potential for this current under these conditions does not change. Vice versa, influences determined by changes in the geometry and ion conductance of the dendrite membrane are capable not only of decreasing the current injected into the soma but also of changing its reversal potential. The thinner the dendrite and the more distant the location of the synapse from the soma, the more significant such effects. Neirofiziologiya/Neurophysiology, Vol. 37, No. 2, pp. 101–107, March–April, 2005.     

Remote Modulation of Current Transfer from Dendritic Glutamatergic Synapses by GABA-ergic Synapses of the Somatic Zone of Motoneurons: a Simulation Study

Until now, information concerning spatial interaction of postsynaptic excitation and inhibition in neuronal dendrites remains rather limited. In model experiments, we studied spatial effects of tonic co-activation of GABA-ergic synapses situated on the soma and axon hillock of a motoneuron and dendritic glutamatergic synapses with receptors sensitive or insensitive to N-methyl-D-aspartate. We analyzed distribution maps of the transmembrane potentials and excitatory currents transferred toward the soma over the reconstructed dendritic arborization of a rat abducens motoneuron (three-dimensional reconstruction). In the motoneuron, isolated tonic excitation of glutamatergic synapses induced two stable states of low (downstate) or high (upstate) spatially heterogeneous dendritic depolarization, which decayed with unequal rates along different dendritic paths. In this case, the local steady-state current-voltage relation of the dendritic membrane became N-shaped due to a limb of the negative slope within a certain voltage range. The upstate corresponding to plateau potentials associated with stereotyped motor activity patterns was analyzed in detail. In this state, most proximal dendritic sites were the main sources of the excitatory current reaching the soma, while the contribution from distal sites was negligible. Co-activation of GABA-synapses located at the soma and axon hillock reduced this depolarization and shifted the main excitatory current source from a perisomatic location to the middle, structurally more complex, region of the dendritic arborization. The more remote dendritic region having a greater membrane area and receiving a greater number of synaptic contacts became directly involved in the supply of the trigger zone by the excitatory current. We suggest that a special, not described earlier, operational mechanism of postsynaptic inhibition is manifested in the above spatial effects of activation of strategically located inhibitory synapses, and that the list of known crucial inhibitory mechanisms (namely hyperpolarization and shunting of the postsynaptic membrane) must be expanded.     

Inhibitory postsynaptic potentials carry synchronized frequency information in active cortical networks

Temporal precision in spike timing is important in cortical function, interactions, and plasticity. We found that, during periods of recurrent network activity (UP states), cortical pyramidal cells in vivo and in vitro receive strong barrages of both excitatory and inhibitory postsynaptic potentials, with the inhibitory potentials showing much higher power at all frequencies above approximately 10 Hz and more synchrony between nearby neurons. Fast-spiking inhibitory interneurons discharged strongly in relation to higher-frequency oscillations in the field potential in vivo and possess membrane, synaptic, and action potential properties that are advantageous for transmission of higher-frequency activity. Intracellular injection of synaptic conductances having the characteristics of the recorded EPSPs and IPSPs reveal that IPSPs are important in controlling the timing and probability of action potential generation in pyramidal cells. Our results support the hypothesis that inhibitory networks are largely responsible for the dissemination of higher-frequency activity in cortex.     

Silicon Synaptic Conductances

We have developed compact analog integrated circuits that simulate two synaptic excitatory conductances. A four-transistor circuit captures the dynamics of an excitatory postsynaptic current caused by a real AMPA conductance. A six-transistor circuit simulates the effects of a real voltage-dependent NMDA conductance. The postsynaptic current dynamics are modeled by a current mirror integrator with adjustable gain. The voltage dependence of the silicon NMDA conductance is realized by a differential pair. We show the operation of these silicon synaptic conductances and their integration with the silicon neuron (Mahowald and Douglas, 1991).     

Estimating three synaptic conductances in a stochastic neural model

We present a method for the reconstruction of three stimulus-evoked time-varying synaptic input conductances from voltage recordings. Our approach is based on exploiting the stochastic nature of synaptic conductances and membrane voltage. Starting with the assumption that the variances of the conductances are known, we use a stochastic differential equation to model dynamics of membrane potential and derive equations for first and second moments that can be solved to find conductances. We successfully apply the new reconstruction method to simulated data. We also explore the robustness of the method as the assumptions of the underlying model are relaxed. We vary the noise levels, the reversal potentials, the number of stimulus repetitions, and the accuracy of conductance variance estimation to quantify the robustness of reconstruction. These studies pave the way for the application of the method to experimental data.     

Balanced Excitatory and Inhibitory Synaptic Currents Promote Efficient Coding and Metabolic Efficiency

A balance between excitatory and inhibitory synaptic currents is thought to be important for several aspects of information processing in cortical neurons in vivo, including gain control, bandwidth and receptive field structure. These factors will affect the firing rate of cortical neurons and their reliability, with consequences for their information coding and energy consumption. Yet how balanced synaptic currents contribute to the coding efficiency and energy efficiency of cortical neurons remains unclear. We used single compartment computational models with stochastic voltage-gated ion channels to determine whether synaptic regimes that produce balanced excitatory and inhibitory currents have specific advantages over other input regimes. Specifically, we compared models with only excitatory synaptic inputs to those with equal excitatory and inhibitory conductances, and stronger inhibitory than excitatory conductances (i.e. approximately balanced synaptic currents). Using these models, we show that balanced synaptic currents evoke fewer spikes per second than excitatory inputs alone or equal excitatory and inhibitory conductances. However, spikes evoked by balanced synaptic inputs are more informative (bits/spike), so that spike trains evoked by all three regimes have similar information rates (bits/s). Consequently, because spikes dominate the energy consumption of our computational models, approximately balanced synaptic currents are also more energy efficient than other synaptic regimes. Thus, by producing fewer, more informative spikes approximately balanced synaptic currents in cortical neurons can promote both coding efficiency and energy efficiency.