Time Course Of Postsynaptic Potentials Research Articles

The role of negative conductances in neuronal subthreshold properties and synaptic integration.

Based on passive cable theory, an increase in membrane conductance produces a decrease in the membrane time constant and input resistance. Unlike the classical leak currents, voltage-dependent currents have a nonlinear behavior which can create regions of negative conductance, despite the increase in membrane conductance (permeability). This negative conductance opposes the effects of the passive membrane conductance on the membrane input resistance and time constant, increasing their values and thereby substantially affecting the amplitude and time course of postsynaptic potentials at the voltage range of the negative conductance. This paradoxical effect has been described for three types of voltage-dependent inward currents: persistent sodium currents, L- and T-type calcium currents and ligand-gated glutamatergic N-methyl-D-aspartate currents. In this review, we describe the impact of the creation of a negative conductance region by these currents on neuronal membrane properties and synaptic integration. We also discuss recent contributions of the quasi-active cable approximation, an extension of the passive cable theory that includes voltage-dependent currents, and its effects on neuronal subthreshold properties.

Analytical Integrate-and-Fire Neuron Models with Conductance-Based Dynamics and Realistic Postsynaptic Potential Time Course for Event-Driven Simulation Strategies

In a previous paper (Rudolph & Destexhe, 2006), we proposed various models, the gIF neuron models, of analytical integrate-and-fire (IF) neurons with conductance-based (COBA) dynamics for use in event-driven simulations. These models are based on an analytical approximation of the differential equation describing the IF neuron with exponential synaptic conductances and were successfully tested with respect to their response to random and oscillating inputs. Because they are analytical and mathematically simple, the gIF models are best suited for fast event-driven simulation strategies. However, the drawback of such models is they rely on a nonrealistic postsynaptic potential (PSP) time course, consisting of a discontinuous jump followed by a decay governed by the membrane time constant. Here, we address this limitation by conceiving an analytical approximation of the COBA IF neuron model with the full PSP time course. The subthreshold and suprathreshold response of this gIF4 model reproduces remarkably well the postsynaptic responses of the numerically solved passive membrane equation subject to conductance noise, while gaining at least two orders of magnitude in computational performance. Although the analytical structure of the gIF4 model is more complex than that of its predecessors due to the necessity of calculating future spike times, a simple and fast algorithmic implementation for use in large-scale neural network simulations is proposed.

Role of active dendritic conductances in subthreshold input integration

Dendrites of many types of neurons contain voltage-dependent conductances that are active at subthreshold membrane potentials. To understand the computations neurons perform it is key to understand the role of active dendrites in the subthreshold processing of synaptic inputs. We examine systematically how active dendritic conductances affect the time course of postsynaptic potentials propagating along dendrites, and how they affect the interaction between such signals. Voltage-dependent currents can be classified into two types that have qualitatively different effects on subthreshold input responses: regenerative dendritic currents boost and broaden EPSPs, while restorative currents attenuate and narrow EPSPs. Importantly, the effects of active dendritic currents on EPSP shape increase as the EPSP travels along the dendrite. The effectiveness of active currents in modulating the EPSP shape is determined by their activation time constant: the faster it is, the stronger the effect on EPSP amplitude, while the largest effects on EPSP width occur when it is comparable to the membrane time constant. We finally demonstrate that the two current types can differentially improve precision and robustness of neural computations: restorative currents enhance coincidence detection of dendritic inputs, whereas direction selectivity to sequences of dendritic inputs is enhanced by regenerative dendritic currents.

Analytical integrate-and-fire neuron models with conductance-based dynamics and realistic PSP time course for event-driven simulation strategies

Recently, we developed models of analytical integrateand-fire (IF) neurons with conductance-based (COBA) dynamics, the gIF neuron models [1]. These models are based on an analytical approximation of the differential equation describing the IF neuron with exponential synaptic conductances and were successfully tested with respect to their response to random and oscillating inputs. Due to their simple mathematical structure, the gIF models are best suited for fast, event-driven simulation strategies. However, the approximations were based on the assumption of instantaneous rise and exponential decay of the postsynaptic potential (PSP). Consequent to this instantaneous rise, spikes were always produced at the onset of the PSP, which might have consequences for the temporal precision of the cellular responses, as the finite rise time of the PSP and the consequent delay between the onset of synaptic input and spike were not present in this model.

Dendritic amplification of inhibitory postsynaptic potentials in a model Purkinje cell

In neurons with large dendritic arbors, the postsynaptic potentials interact in a complex manner with active and passive membrane properties, causing not easily predictable transformations during the propagation from synapse to soma. Previous theoretical and experimental studies in both cerebellar Purkinje cells and neocortical pyramidal neurons have shown that voltage-dependent ion channels change the amplitude and time-course of postsynaptic potentials. We investigated the mechanisms involved in the propagation of inhibitory postsynaptic potentials (IPSPs) along active dendrites in a model of the Purkinje cell. The amplitude and time-course of IPSPs recorded at the soma were dependent on the synaptic distance from the soma, as predicted by passive cable theory. We show that the effect of distance on the amplitude and width of the IPSP was significantly reduced by the dendritic ion channels, whereas the rise time was not affected. Somatic IPSPs evoked by the activation of the most distal synapses were up to six times amplified owing to the presence of voltage-gated channels and the IPSP width became independent of the covered distance. A transient deactivation of the Ca(2+) channels and the Ca(2+)-dependent K(+) channels, triggered by the hyperpolarization following activation of the inhibitory synapse, was found to be responsible for these dynamics. Nevertheless, the position of activated synapses had a marked effect on the Purkinje cell firing pattern, making stellate cells and basket cells most suitable for controlling the firing rate and spike timing, respectively, of their target Purkinje cells.

Detection of Spontaneous Postsynaptic Potentials

The amplitude and time course of postsynaptic potentials (PSPs) recorded by intracellular techniques contain information that allow different synaptic events to be detected. In the present paper an algorithm to detect spontaneous PSPs is described. The algorithm is based on computation of approximation of first and second derivatives of the signals. The method was tested on both computer-simulated potentials and on experimental data recorded from dissociated mouse spinal cord neurons in tissue culture. The receiver operating characteristics of the detection algorithm were computed. This method can be applied to investigations of dynamic changes in the activity of neural networks.

Single axon fast inhibitory postsynaptic potentials elicited by a sparsely spiny interneuron in rat neocortex.

Many of the different morphological types of interneurons in mammalian neocortex are presumed to be inhibitory, but to date, conclusive functional data have been lacking. Using paired intracellular recordings in slices of adult rat somatosensory cortex, we present a sparsely spiny, burst firing interneuron that elicits in a simultaneously recorded pyramid a fast inhibitory postsynaptic potential, reversing at -78 mV. Neither inhibitory postsynaptic potential time course, nor paired pulse depression (inter-spike interval 15-120 ms), was affected by addition of the GABAB antagonist/partial agonist 2-OH-Saclofen (250 microM), but increasing extracellular [Ca2+] enhanced inhibitory postsynaptic potential amplitude at low firing rates and increased paired pulse depression at higher rates. Light microscopic examination of the biocytin-filled neurons revealed the presynaptic cell to be a sparsely spiny interneuron and the postsynaptic to be a small pyramidal neuron, both in layer II. Ultrastructural examination of 16 terminals of the presynaptic interneuron revealed that they formed symmetric contacts with unlabelled neurons, four with neuronal somata, 10 with dendritic shafts and two with spine shafts. This, therefore, is the first report of the properties of a single axon inhibitory postsynaptic potential in neocortex resulting from action potentials in an electro-physiologically and morphologically identified interneuron. We propose that at least some of the sparsely spiny, burst firing interneurons inhibit pyramidal neurons via GABAA receptors.

Waveform parameters of recurrent inhibitory postsynaptic potentials in cat motoneurons during time-varying activation patterns

A considerable number of theoretical and experimental studies have been undertaken to establish quantitative relationships between the time course of postsynaptic potentials in a neuron and the change in firing probability thereby induced. Depending on background synaptic noise level, the time course of the postsynaptic potential per se as well as its time derivative are both of importance in varying proportion. We have recently begun to study recurrent inhibitory potentials in cat hindlimb motoneurons during rhythmically varying rates of stimulation of motor axons. The amplitude-rate relationship exhibits hysteresis in that amplitudes are usually larger during augmenting than decrementing rates in the cycle. We here report results on the other important variable, that is the slope of recurrent inhibitory potential development, which need not a priori be correlated with amplitude. We found that the slope has a relation to stimulus rate similar to amplitude, so that both parameters are correlated. In pentobarbitone anaesthetized or decerebrate cats, intracellular recordings were obtained from hindlimb skeleto-motoneurons. Various hindlimb muscle nerves were prepared for electrical stimulation to elicit recurrent inhibitory potentials, with dorsal roots cut. Test stimulus patterns consisted of repetitive pulse trains whose rates varied, at modulation frequencies between 0.1 and 1.0 Hz, in one of two waveforms: triangular or sinusoidal. Modulation depths were either “full”, with rates varying between a minimum of less than 10 and a maximum of around 50 pulses per s. Or they were about “half” this depth, with mean rates shifted into a “low”, “medium” or “high” rate region. Recurrent inhibitory potentials were averaged with respect to stimuli occurring during different phases of the stimulation cycle. Most often when, throughout the cycle, the amplitude changed in a consistent way, so did the slopes of the inhibitory potentials. That is, when the amplitudes rhythmically declined with increasing and recovered with decreasing stimulus rate, the rate of hyperpolarization followed the same pattern. With prominent hysteresis in amplitude, a corresponding hysteresis appeared in slopes. Hence, amplitude and slopes were correlated, occasionally showing a hysteresis among themselves. To a certain extent, these results can be explained by Renshaw cell behaviour, the contribution of the Renshaw cell-motoneuron synapse being unknown and difficult to assess experimentally. For the inhibitory effect of Renshaw cells on motoneurons (and reciprocal Ia inhibitory interneurons), both its magnitude and its time course probably play an important role in determining the efficacy of counteracting local excitatory inputs. The change in slope of inhibitory potentials, and likely its underlying conductance, during cyclic motoneuron activation can be presumed to significantly contribute to the temporal pattern of discharge of motoneurons, in particular in relation to the prevention of synchronization leading to enhanced tremor.

Endo-exocytotic images and changes in synaptic transmission induced by diamide at a cholinergic junction

Small tissue fragments excised from the electric organ of Torpedo marmorata were treated with diamide, a penetrating thiol oxidizing agent, until synaptic transmission was blocked. At this stage, we found an unexpected number of exo-endocytotic images in the presynaptic plasmalemma. Omega-shaped profiles, some of them coated, were seen in thin sections of fixed tissue and pits opened in the P-face of the presynaptic membrane in freeze-fracture replicas from rapidly-frozen preparations. Diamide-treated specimens were frozen at 1 ms time intervals before, during and after a single electrical stimulus. This stimulation did not result in a further increase in the density of presynaptic pits, not in any change affecting the density or size distribution of intramembrane particles. This result is in contrast with what is observed in untreated specimens where transmission of a nerve impulse is accompanied by a momentary rise in the number of large particles. The density of synaptic vesicles—especially that of a subpopulation of small size vesicles—transiently increased within the first 2 h of diamide treatment. During the first stages of intoxication, diamide prolonged the time course of postsynaptic potentials—both spontaneous and evoked—probably by altering the gating properties of receptors (acetylcholinesterase activity was not impaired). Later on, all evoked responses were blocked. The spontaneous transmitter release greatly increased, first in the form of quantal miniature potentials. These then subsided whereas a class of very small potentials was generated at a high frequency. Also under the action of diamide, 45 calcium progressively accumulated in the tissue but the number of synaptic vesicles containing calcium deposits was reduced. It is concluded that diamide causes a marked increase in the number of exo-endocytotic images in the presynaptic membrane, suppresses quantal but not subquantal release, and interferes with calcium sequestration in and extrusion from terminals.