Diphasic postsynaptic potential: a chemical synapse capable of mediating conjoint excitation and inhibition

Two identified interneurons in each buccal ganglion of Aplysia can mediate conjoined excitation and inhibition to a single follower cell. A single presynaptic action potential in one of these interneurons produces a diphasic, depolarizing-hyperpolarizing synaptic potential apparently as a result of a single transmitter acting on two types of postsynaptic receptors in the follower cell. These receptors produce synaptic potentials with differing reversal potentials, ionic conductances, time courses, rates of decrement with repetition, pharmacological properties, and functional consequences. The excitatory receptor controls a sodium conductance, the inhibitory receptor controls a chloride conductance. Both components of the synaptic potentials can be produced by iontophoretic application of acetylcholine on the cell body of the follower cell, and each component is differentially sensitive to different cholinergic blocking agents.     

Combined analog and action potential coding in hippocampal mossy fibers

In the mammalian cortex, it is generally assumed that the output information of neurons is encoded in the number and the timing of action potentials. Here, we show, by using direct patchclamp recordings from presynaptic hippocampal mossy fiber boutons, that axons transmit analog signals in addition to action potentials. Excitatory presynaptic potentials result from subthreshold dendritic synaptic inputs, which propagate several hundreds of micrometers along the axon and modulate action potential-evoked transmitter release at the mossy fiber-CA3 synapse. This combined analog and action potential coding represents an additional mechanism for information transmission in a major hippocampal pathway.     

Extracellular potassium ions mediate specific neuronal interaction

The giant interneurons from the nerve system of the cockroach Periplaneta americana exhibit a peculiar reciprocal synaptic interaction. The synaptic potentials are not blocked by addition of 5 millimolar cobalt chloride and have an extrapolated reversal potential close to 0 millivolt. Hyperpolarizing current injected into one cell does not spread to the other. Intracellular injection of tetraethylammonium ions into one giant interneuron increases the duration of the action potential of the injected cell to 30 milliseconds and reduces the rise time and amplitude of the postsynaptic response recorded in the other giant interneuron. These results indicate that the interaction between the interneurons is not mediated by conventional chemical or electrotonic synapses.. All evidence points to generation of the potentials by localized increases in extracellular potassium concentrations as a consequence of firing of one neuron.     

Regulation of dendritic protein synthesis by miniature synaptic events

We examined dendritic protein synthesis after a prolonged blockade of action potentials alone and after a blockade of both action potentials and miniature excitatory synaptic events (minis). Relative to controls, dendrites exposed to a prolonged blockade of action potentials showed diminished protein synthesis. Dendrites in which both action potentials and minis were blocked showed enhanced protein synthesis, suggesting that minis inhibit dendritic translation. When minis were acutely blocked or stimulated, an immediate increase or decrease, respectively, in dendritic translation was observed. Taken together, these results reveal a role for miniature synaptic events in the acute regulation of dendritic protein synthesis in neurons.     

Dendritic spikes and their inhibition in alligator Purkinje cells

Alligator Purkinje cells generate action potentials in the peripheral dendritic tree, after synaptic depolarization via superficial parallel fibers. These action potentials are inhibited at the dendrite level by preceding parallel-fiber volleys at close intervals. We conclude that this inhibition is produced by the activation of the inhibitory interneurons of the molecular layer, the stellate cells, which establish synaptic contacts with the dendrites of the Purkinje cells.     

Locally synchronized synaptic inputs

Synaptic inputs on dendrites are nonlinearly converted to action potential outputs, yet the spatiotemporal patterns of dendritic activation remain to be elucidated at single-synapse resolution. In rodents, we optically imaged synaptic activities from hundreds of dendritic spines in hippocampal and neocortical pyramidal neurons ex vivo and in vivo. Adjacent spines were frequently synchronized in spontaneously active networks, thereby forming dendritic foci that received locally convergent inputs from presynaptic cell assemblies. This precise subcellular geometry manifested itself during N-methyl-D-aspartate receptor-dependent circuit remodeling. Thus, clustered synaptic plasticity is innately programmed to compartmentalize correlated inputs along dendrites and may reify nonlinear synaptic integration.     

Hemodynamic signals correlate tightly with synchronized gamma oscillations

Functional imaging methods monitor neural activity by measuring hemodynamic signals. These are more closely related to local field potentials (LFPs) than to action potentials. We simultaneously recorded electrical and hemodynamic responses in the cat visual cortex. Increasing stimulus strength enhanced spiking activity, high-frequency LFP oscillations, and hemodynamic responses. With constant stimulus intensity, the hemodynamic response fluctuated; these fluctuations were only loosely related to action potential frequency but tightly correlated to the power of LFP oscillations in the gamma range. These oscillations increase with the synchrony of synaptic events, which suggests a close correlation between hemodynamic responses and neuronal synchronization.     

Acetylcholine and GABA mediate opposing actions on neuronal chloride channels in crayfish

A central principle of neural integration is that excitatory and inhibitory neurotransmitters effect the opening of distinct classes of membrane ionic channels and that integration consists of the summation of the opposing ionic currents on the postsynaptic membrane. In tangential cells of crayfish optic lobes, a hyperpolarizing, biphasic synaptic potential is produced by the concurrent action of acetylcholine and gamma aminobutyric acid (GABA). Acetylcholine hyperpolarizes the cell and increases chlorine conductance. GABA depolarizes the cell by closing some of the same chloride channels. Therefore, in this case integration is achieved by the antagonistic actions of two transmitters on the same ionic channel.     

Adenosine 3',5'-monophosphate: electrophysiological evidence for a role in synaptic transmission

Synaptic potentials and changes in resting membrane potentials of superior cervical ganglia of the rabbit were measured in the presence of adenosine 3',5'-monophosphate and agents that affect its metabolism. Adenosine 3',5'-monophosphate and its mono- and dibutyryl derivatives caused a hyperpolarization of the postganglionic neurons. Theophylline potentiated the slow inhibitory postsynaptic potential that follows synaptic transmission, as well as the hyperpolarization of postganglionic neurons caused by exogenous dopamine. Conversely, prostaglandin E(1) inhibited both the slow inhibitory postsynaptic potential and the dopamine-induced hyperpolarization. We hypothesize that the slow inhibitory postsynaptic potential as well as the dopamine-induced hyperpolarization result from increased amounts of adenosine 3'5'-monophosphate in the postganglionic neurons. The dibutyryl derivative of guanosine 3'5'-monophosphate caused a depolarization of the postganglionic neurons, which is consistent with the possibility that guanosine 3'5'-monophosphate mediates synaptic transmission at muscarinic cholinergic synapses.     

A direct synaptic connection mediating both excitation and inhibition

Neurons have generally been thought to produce only one synaptic action on any particular cell which they innervate. An identified interneuron in the abdominal ganglion of Aplysia mediates both direct excitation and inhibition to an identified follower cell. At low firing rates the interneuron produces excitatory postsynaptic potentials; however at higher firing rates these gradually diminish in size and eventually invert to inhibitory postsynaptic potentials. Electrophysiological and pharmacological evidence indicates that the connection between these cells is monosynaptic, and that a single transmitter, acetylcholine, mediates both actions. These opposite synaptic responses appear to result from the transmitter's acting on two types of postsynaptic receptors having different thresholds for activation and different susceptibilities for desensitization.     

Activity-induced potentiation of developing neuromuscular synapses

Electrical activity plays a critical role in shaping the structure and function of synaptic connections in the nervous system. In Xenopus nerve-muscle cultures, a brief burst of action potentials in the presynaptic neuron induced a persistent potentiation of neuromuscular synapses that exhibit immature synaptic functions. Induction of potentiation required an elevation of postsynaptic Ca2+ and expression of potentiation appeared to involve an increased probability of transmitter secretion from the presynaptic nerve terminal. Thus, activity-dependent persistent synaptic enhancement may reflect properties characteristic of immature synaptic connections, and bursting activity in developing spinal neurons may promote functional maturation of the neuromuscular synapse.     

Dependence of EPSP efficacy on synapse location in neocortical pyramidal neurons

Neurons receive thousands of synaptic inputs throughout elaborate dendritic trees. Here we determine the somatic impact of excitatory postsynaptic potentials (EPSPs) generated at known dendritic sites in neocortical pyramidal neurons. As inputs became more distal, somatic EPSP amplitude decreased, whereas use-dependent depression increased. Despite marked attenuation (>40-fold), when coactivated within a narrow time window (approximately 10 milliseconds), distal EPSPs could directly influence action potential output following dendritic spike generation. These findings reveal that distal EPSPs are ineffective sources of background somatic excitation, but through coincidence detection have a powerful transient signaling role.     

Synaptic activation of an electrogenic sodium pump

An identified molluscan interneuron mediates different cholinergic synaptic actions by increasing the conductance of its follower cells to different ions. We have now found that this interneuron also mediates a new class of synaptic actions which does not involve a conductance change but the activation of an electrogenic sodium pump. This synaptic action results in a prolonged inhibitory synaptic potential which is dependent on metabolism and is selectively blocked by cooling and ouabain. In cells which have this synaptic potential, part of the resting membrane potential is also maintained by an electrogenic sodium pump. The same transmitter, acetylcholine, can independently stimulate both a chloride ion conductance and a sodium pump mechanism in the same follower cell by acting on two different postsynaptic receptors.     

Neuronal activity regulates diffusion across the neck of dendritic spines

In mammalian excitatory neurons, dendritic spines are separated from dendrites by thin necks. Diffusion across the neck limits the chemical and electrical isolation of each spine. We found that spine/dendrite diffusional coupling is heterogeneous and uncovered a class of diffusionally isolated spines. The barrier to diffusion posed by the neck and the number of diffusionally isolated spines is bidirectionally regulated by neuronal activity. Furthermore, coincident synaptic activation and postsynaptic action potentials rapidly restrict diffusion across the neck. The regulation of diffusional coupling provides a possible mechanism for determining the amplitude of postsynaptic potentials and the accumulation of plasticity-inducing molecules within the spine head.     

Ribonucleic acid metabolism of a single neuron: correlation with electrical activity

The giant neuron of the abdominal ganglion of Aplysia californica incorporates tritiated uridine into RNA at a constant rate at rest. This rate incrceases under synaptic stimulation, the increase being directly proportional to the number of action potentials produced by the neuron. Multineuronal samples from stimulated ganglia faiiled to show an increase in incorporation.     

Crayfish muscle fiber: ionic requirements for depolarizing synaptic electrogenesis

Presence of sodium in the bathing medium is not essential for the electrically excitable depolarizing electrogenesis of crayfish muscle fibers, production of action potentials being dependent on calcium. The depolarizing electrogenesis of the excitatory synaptic membrane component does require sodium, however, and this ion cannot be replaced by lithium as it can in spike electrogenesis of many cells. Ionophoretic applications of glutamate, which in the presence of sodium depolarize the cell by activating the excitatory synaptic membrane, are without effect in the absence of sodium. Not only is there no depolarization, but the membrane conductance also remains unchanged. Thus, in the absence of inward movement of sodium across the synaptic membrane there is also no outward movement of potassium. Accordingly, it seems that increased conductance for potassium is not an independent process in the synaptic membrane, whereas it is independent of sodium activation in spike electrogenesis. Chloride activation is independent, however; increase in conductance and the electrogenesis of the inhibitory synaptic component are not affected by the absence of sodium. Implications of these findings regarding the structure of differently excitable membrane components are discussed.     

Simultaneously recorded trains of action potentials: analysis and functional interpretation

A new kind of statistical display, the joint peri-stimulus-time scatter diagram, facilitates the analysis and interpretation of two or more simultaneously recorded trains of action potentials. The display is a generalization of the cross correlation and the peri-stimulus-time histogram, and it reflects specific underlying neuronal interactions. The technique yields quantitative measures of interaction in terms of effectiveness of synaptic connections.     

Intracellular potentials of cortical neurons during focal epileptogenic discharges

Focal electroencephalographic discharges in lesions of cortex induced by freezing are associated with prolonged membrane depolarizations and hyperpolarizations in neurons located at various depths in the lesion sites. Transmembrane potential changes have properties similar to those of postsynaptic potentials. The temporal relationship between intracellular potentials and paroxysmal discharges indicates that the latter are extracellularly recorded summations of synchronously developing depolarizations and hyperpolarizations in complex synaptic organizations of neurons.     

Command neurons in Pleurobranchaea receive synaptic feedback from the motor network they excite

Command neurons that cause rhythmic feeding behavior in the marine mollusc Pleurobranchaea californica have been identified in the cerebropleural ganglion (brain). Intracellular stimulation of single command neurons in isolated nervous systems, semi-intact prepartions, and restrained whole animals causes the same rhythmic motor output pattern as occurs during feeding. During this motor output pattern, action potentials recorded intracellularly from the command neurons occur in cyclic bursts that are phase-locked with the feeding rhythm. This modulation results from repetitive, alternating bursts of excitatory and inhibitory postsynaptic potentials, which are caused at least in part by synaptic feedback to the command neurons from identified classes of neurons in the feeding network. Central feedback to command neurons from the motor network they excite provides a possible general physiological mechanism for the sustained oscillation of neural networks controlling cyclic behavior.