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PubMed2002

Calcium waves and closure of potassium channels in response to GABA stimulation in Hermissenda type B photoreceptors.

Classical conditioning of Hermissenda crassicornis requires the paired presentation of a conditioned stimulus (light) and an unconditioned stimulus (turbulence). Light stimulation of photoreceptors leads to production of diacylglycerol, an activator of protein kinase C, and inositol triphosphate (IP(3)), which releases calcium from intracellular stores. Turbulence causes hair cells to release GABA onto the terminal branches of the type B photoreceptor. One prior study has shown that GABA stimulation produces a wave of calcium that propagates from the terminal branches to the soma and raises the possibility that two sources of calcium are required for memory storage. GABA stimulation also causes an inhibitory postsynaptic potential (IPSP) followed by a late depolarization and increase in input resistance, whose cause has not been identified. A model was developed of the effect of GABA stimulation on the Hermissenda type B photoreceptor to evaluate the currents underlying the late depolarization and to evaluate whether a calcium wave could propagate from the terminal branches to the soma. The model included GABA(A), GABA(B), and calcium-sensitive potassium leak channels; calcium dynamics including release of calcium from intracellular stores; and the biochemical reactions leading from GABA(B) receptor activation to IP(3) production. Simulations show that it is possible for a wave of calcium to propagate from the terminal branches to the soma. The wave is initiated by IP(3)-induced calcium release but propagation requires release through the ryanodine receptor channel where IP(3) concentration is small. Wave speed is proportional to peak calcium concentration at the crest of the wave, with a minimum speed of 9 microM/s in the absence of IP(3). Propagation ceases when peak concentration drops below 1.2 microM; this occurs if the rate of calcium pumping into the endoplasmic reticulum is too large. Simulations also show that both a late depolarization and an increase in input resistance occur after GABA stimulation. The duration of the late depolarization corresponds to the duration of potassium leak channel closure. Neither the late depolarization nor the increase in input resistance are observed when a transient calcium current and a hyperpolarization-activated current are added to the model as replacement for closure of potassium leak channels. Thus the late depolarization and input resistance elevation can be explained by a closure of calcium-sensitive leak potassium currents but cannot be explained by a transient calcium current and a hyperpolarization-activated current.

Adenosine Triphosphatases↗

PubMed2003

Frequency-dependent properties of inhibitory synapses in the rostral nucleus of the solitary tract.

To explore the parameters that define the characteristics of either inhibitory postsynaptic potentials (IPSP) or currents (IPSC) in the gustatory nucleus of the solitary tract (rNST), whole cell patch-clamp recordings were made in horizontal brain stem slices of newborn rats. Neurons were labeled with biocytin to confirm both their location and morphology. IPSPs or IPSCs were evoked by delivering either single, paired-pulse, or tetanic stimulus shocks (0.1-ms duration) via a bipolar stimulating electrode placed on the rNST. Pure IPSP/IPSCs were isolated by the use of glutamate receptor antagonists. For 83% of the single-stimulus-evoked IPSCs, the decay time course was fitted with two exponentials having average time constants of 38 and 181 ms, respectively, while the remainder could be fitted with one exponential of 59 ms. Paired-pulse stimulation resulted in summation of the amplitude of the conditioning and test-stimulus-evoked IPSCs. The decay time course of the test-stimulus-evoked IPSC was slower when compared to the decay time of the conditioning stimulus IPSC. Repeated stimulation resulted in an increase in the decay time of the IPSP/Cs where each consecutive stimulus contributed to prolongation of the decay time constant. Most of the IPSP/Cs resulting from a 1-s >/= 30-Hz tetanic stimulus exhibited an S-shaped decay time course where the amplitude of the IPSP/Cs after termination of the stimulus was initially sustained before starting to decay back to the resting membrane potential. Elevation of extracellular Ca(2+) concentration 10 mM resulted in an increase in the amplitude and decay time of single-stimulus shock-evoked IPSP/Cs. The benzodiazepine GABA(A) receptor modulator diazepam increased the decay time of single-stimulus shock-evoked IPSCs. However, application of diazepam did not affect the decay time of tetanic-stimulation-evoked IPSP/Cs. These results suggest that the decay time of single-stimulus-evoked IPSCs is defined either by receptor kinetics or neurotransmitter clearance from the synaptic cleft or both, while the decay time course of the tetanic stimulus evoked IPSP/Cs is defined by neurotransmitter diffusion from the synaptic cleft. During repetitive stimulation, neurotransmitter accumulates in the synaptic cleft prolonging the decay time constant of the IPSCs. High-frequency stimulation elevates the GABA concentration in the synaptic cleft, which then oversaturates the postsynaptic receptors, and, as a consequence, after termination of the tetanic stimulus, the amplitude of IPSP/Cs is sustained resulting in an S shaped decay time course. This activity-dependent plasticity at GABAergic synapses in the rNST is potentially important in the encoding of taste responses because the dynamic range of stimulus frequencies that result in synaptic plasticity (0-70 Hz) corresponds to the breadth of frequencies that travels via afferent gustatory nerve fibers in response to taste stimuli.

Animals↗

PubMed2007

Effects of mu-opioid receptor modulation on GABAB receptor synaptic function in hippocampal CA1.

Activation of mu-opioid receptors (MORs) alters information coding, synaptic plasticity, and spatial memory in hippocampal CA1. In CA1, MORs act by inhibiting GABA release onto both GABA(A) and GABA(B) receptors exclusively. MOR activation can facilitate excitatory inputs in CA1 dendritic layers by inhibiting synaptic activation of GABA(A) receptors. In this study, we use voltage-sensitive dye imaging to show that MOR activation by the MOR agonist DAMGO suppressed GABA(B) inhibitory postsynaptic potentials in all layers of CA1. When stimulating excitatory input in stratum oriens (SO), stratum radiatum (SR), or stratum lacunosum-moleculare (SLM) with five pulses at 20 Hz in the presence of bicuculline (50 microM), DAMGO (1 muM) was most effective at increasing the amplitude of the last excitatory event. This effect was reversed by the MOR antagonist CTOP (1 muM) and occluded by the GABA(B) receptor agonist CGP 55845 (10 microM). DAMGO was less effective at increasing the amplitude of later excitatory events compared with the effect of CGP 55845. DAMGO was relatively ineffective at increasing the amplitude of excitatory inputs in SLM but had significantly greater effects on excitatory events as they propagated to stratum pyramidale (SP). When stimulating in SR, DAMGO was least effective at increasing excitatory amplitudes in SLM and most effective in SP and SO. Finally, DAMGO was equally effective at increasing excitatory activity amplitudes in all layers of CA1 after stimulating in SO. Therefore MOR suppresses GABA(B) synaptic hyperpolarizations in all layers of CA1 and most effectively facilitates excitatory activity in CA1 output layers.

Analgesics, Opioid↗

PubMed2004

Inhibition of afferent transmission in the feeding circuitry of aplysia: persistence can be as important as size.

We are studying afferent transmission from a mechanoafferent, B21, to a follower, B8. During motor programs, afferent transmission is regulated so that it does not always occur. Afferent transmission is eliminated when spike propagation in B21 fails, i.e., when spike initiation is inhibited in one output region-B21's lateral process. Spike initiation in the lateral process is inhibited by the B52 and B4/5 cells. Individual B52 and B4/5-induced inhibitory postsynaptic potentials (IPSPs) in B21 differ. For example, the peak amplitude of a B4/5-induced IPSP is four times the amplitude of a B52 IPSP. Nevertheless, when interneurons fire in bursts at physiological (i.e., low) frequencies, afferent transmission is most effectively reduced by B52. Although individual B52-induced IPSPs are small, they have a long time constant and summate at low firing frequencies. Once IPSPs summate, they effectively block afferent transmission. In contrast, individual B4/5-induced IPSPs have a relatively short time constant and do not summate at low frequencies. B52 and B4/5 therefore differ in that once synaptic input from B52 becomes effective, afferent transmission is continuously inhibited. In contrast, periods of B4/5-induced inhibition are interspersed with relatively long intervals in which inhibition does not occur. Consequently, the probability that afferent transmission will be inhibited is low. In conclusion, it is widely recognized that afferent transmission can be regulated by synaptic input. Our experiments are, however, unusual in that they relate specific characteristics of postsynaptic potentials to functional inhibition. In particular we demonstrate the potential importance of the IPSP time constant.

Action Potentials↗

PubMed2006

Distinctive glycinergic currents with fast and slow kinetics in thalamus.

We examined functional properties of inhibitory postsynaptic currents (IPSCs) evoked by medial lemniscal stimulation, spontaneous IPSCs (sIPSCs), and single-channel, extrasynaptic currents evoked by glycine receptor agonists or gamma-aminobutyric acid (GABA) in rat ventrobasal thalamus. We identified synaptic currents by reversal at E(Cl) and sensitivity to elimination by strychnine, GABA(A) antagonists, or combined application. Glycinergic IPSCs featured short (about 12 ms) and long (about 80 ms) decay time constants. These fast and slow IPSCs occurred separately with monoexponential decays, or together with biexponential decay kinetics. Glycinergic sIPSCs decayed monoexponentially with time constants, matching fast and slow IPSCs. These findings were consistent with synaptic responses generated by two populations of glycine receptors, localized under different nerve terminals. Glycine, taurine, or beta-alanine applied to excised membrane patches evoked short- and long-duration current bursts. Extrasynaptic burst durations resembled fast and slow IPSC time constants. The single, intermediate time constant (about 22 ms) of GABA(A)ergic IPSCs cotransmitted with glycinergic IPSCs approximated the burst duration of extrasynaptic GABA(A) channels. We noted differences between synaptic and extrasynaptic receptors. Endogenously activated glycine and GABA(A) receptor channels had higher Cl- permeability than that of their extrasynaptic counterparts. The beta-amino acids activated long-duration bursts at extrasynaptic glycine receptors, consistent with a role in detection of ambient taurine or beta-alanine. Heterogeneous kinetics and permeabilities implicate molecular and functional diversity in thalamic glycine receptors. Fast, intermediate, and slow inhibitory postsynaptic potential decays, mostly attributed to cotransmission by glycinergic and GABAergic pathways, allow for discriminative modulation and integration with voltage-dependent currents in ventrobasal neurons.

Action Potentials↗

PubMed2003

A corollary discharge mechanism modulates central auditory processing in singing crickets.

Crickets communicate using loud (100 dB SPL) sound signals that could adversely affect their own auditory system. To examine how they cope with this self-generated acoustic stimulation, intracellular recordings were made from auditory afferent neurons and an identified auditory interneuron-the Omega 1 neuron (ON1)-during pharmacologically elicited singing (stridulation). During sonorous stridulation, the auditory afferents and ON1 responded with bursts of spikes to the crickets' own song. When the crickets were stridulating silently, after one wing had been removed, only a few spikes were recorded in the afferents and ON1. Primary afferent depolarizations (PADs) occurred in the terminals of the auditory afferents, and inhibitory postsynaptic potentials (IPSPs) were apparent in ON1. The PADs and IPSPs were composed of many summed, small-amplitude potentials that occurred at a rate of about 230 Hz. The PADs and the IPSPs started during the closing wing movement and peaked in amplitude during the subsequent opening wing movement. As a consequence, during silent stridulation, ON1's response to acoustic stimuli was maximally inhibited during wing opening. Inhibition coincides with the time when ON1 would otherwise be most strongly excited by self-generated sounds in a sonorously stridulating cricket. The PADs and the IPSPs persisted in fictively stridulating crickets whose ventral nerve cord had been isolated from muscles and sense organs. This strongly suggests that the inhibition of the auditory pathway is the result of a corollary discharge from the stridulation motor network. The central inhibition was mimicked by hyperpolarizing current injection into ON1 while it was responding to a 100 dB SPL sound pulse. This suppressed its spiking response to the acoustic stimulus and maintained its response to subsequent, quieter stimuli. The corollary discharge therefore prevents auditory desensitization in stridulating crickets and allows the animals to respond to external acoustic signals during the production of calling song.

Acoustic Stimulation↗

PubMed1976

Effects of dorsal column stimulation on primate spinothalamic tract neurons.

The effect of dorsal column stimulation on spinothalamic tract cells was investigated in anesthetized monkeys. The dorsal column stimuli were applied at midthoracic or at cervical levels of the cord, while the responses of spinothalamic tract cells of the lumbosacral enlargement were examined. A dorsal column volley depressed the activity of spinothalamic tract cells for about 150 ms. A similar depression was observed whether the spinothalamic tract cell was classified as hair activated, low, or high threshold, based on its response properties to cutaneous stimulation. The hair-activated and low-threshold spinothalamic tract cells were initially excited by the dorsal column volley, but often it was possible to demonstrate that a depression could be produced by stimuli which were too weak to cause excitation of these cells. Depression was produced both of the responses of spinothalamic tract cells to electrical stimulation of peripheral nerves and to mechanical stimulation of cutaneous nociceptors. A similar depression was produced by electrical stimulation of large afferents in peripheral nerves. The pathway mediating the depression of spinothalamic tract cells was shown to involve antidromic invasion of collaterals of dorsal column fibers. The best points for stimulation of the cord to produce a depression were over the ipsilateral dorsal column. A lesion interrupting the dorsal column eliminated the depression of cells below the lesion, whereas a lesion of much of the lateral column had no effect. The mechanism of the depression is likely to be complex. Apart from interactions at an interneuronal level, dorsal column volleys can be presumed to collide with sensory input from afferents which project up the dorsal column; collision would interfere chiefly with the responses of hair-activated and low-threshold spinothalamic tract cells. In addition, dorsal column volleys were shown to evoke inhibitory postsynaptic potentials in some spinothalamic tract neurons, and they also produced primary afferent depolarization, at least of large cutaneous afferemts. The excitation of hair-activated and low-threshold spinothalamic tract cells argues against their participation in signaling pain, since dorsal column stimulation in humans does not produce pain at stimulus intensities and frequencies which should activate such neurons. Alternatively, an ascending volley in the dorsal column or in other pathways may interfere with pain transmission in the brain.

Animals↗

PubMed1980

Pharmacological dissection of pyloric network of the lobster stomatogastric ganglion using picrotoxin.

1. Picrotoxin (PTX) (10(-7)-10(-6) M) completely blocked most inhibitory synapses in the pyloric pattern generator of the lobster (Panulirus interruptus) stomatogastric ganglion. The sensitivity of synapses from most classes of identified neurons was examined. Blockade was at least partly reversible with prolonged washing. 2. The synapses from pyloric dilator (PD) neurons were the only inhibitory synapses that picrotoxin failed to block completely. 3. A correlation is derived that brief, fast-rise inhibitory postsynaptic potentials (IPSPs) are picrotoxin sensitive, whereas a slow rounded component of IPSPs from PD neurons is not picrotoxin sensitive. 4. Picrotoxin caused specific changes in the pattern of the motor rhythm produced by the 16-cell pyloric network. This sheds some light on the functional role of particular synapses in the pyloric generator. 5. The endogenously bursting neurons (PD and anterior burster (AB)), which drive the pyloric rhythm, kept a similar burst rate. 6. Under picrotoxin, the pyloric "follower" neurons all moved to later phase relative to the "driver" group. Some normally antagonistic cells, related by reciprocal inhibitor connections, became in-phase. These and other pattern changes could be related to blockade of particular synapses. 7. The pyloric rhythm was still quite recognizable under picrotoxin despite the drastically altered circuitry of the synaptic network. This supports the idea that periodic inhibition from the PD driver neurons plays a primary role in creating the pyloric pattern.

Acetylcholine↗

PubMed1982

Mechanisms underlying pattern generation in lobster stomatogastric ganglion as determined by selective inactivation of identified neurons. III. Synaptic connections of electrically coupled pyloric neurons.

1. The pyloric dilator (PD) and anterior burster (AB) neurons in the pyloric system of the lobster stomatogastric ganglion are electrically coupled and synchronously active. We have used the lucifer yellow photoinactivation technique to separate the connections made by the PD motor neurons from those made by the AB interneuron. 2. Photoinactivation of either the two PD neurons or the single AB neuron allowed us to separate the compound inhibitory postsynaptic potentials (IPSPs) in the lateral pyloric (LP) and pyloric (PY) motor neurons resulting from synchronous PD and AB activity into AB-evoked and PD-evoked components. These IPSPs have different time courses, reversal potentials, ion selectivities, and pharmacological properties. 3. Photoinactivation and membrane-potential manipulations indicated that a readily observable IPSP recorded in the AB neuron and correlated with action potentials in the LP neuron is actually an electrotonic potential due to an LP-evoked IPSP in the PD neurons. 4. Selective inactivation of either the two PD neurons or the AB neuron revealed that the IPSP recorded in the ventricular dilator (VD) motor neuron is due solely to AB-released transmitter. 5. The electrical coupling potentials measurable between the AB, PD, and VD neuron somata are due to direct electrical coupling between all of these neurons. 6. Circuit analysis and transmitter identification may be complicated by electrical coupling. We suggest that the presence of electrical coupling between nonidentical neurons may provide a new mechanism that allows changes in synaptic characteristics among neurons within a "hard-wired" circuit.

Animals↗

PubMed1983

Ammonia does not selectively block IPSPs in rat hippocampal pyramidal cells.

Intracellular recordings from CA1 pyramidal cells in the rat hippocampal slice preparation have been used to study the action of ammonia on inhibitory postsynaptic potentials (IPSPs). Concentrations of ammonia less than 2 mM had little effect on IPSPs or the action of iontophoretically applied gamma-aminobutyric acid (GABA). This concentration has been reported to be fully effective in blocking hyperpolarizing IPSPs in spinal cord and neocortex. Concentrations above 2 mM did cause a depolarizing shift in the IPSP and GABA reversal potentials, but this effect was accompanied by several generalized effects. The conductance increase during the IPSP but not during the GABA response was depressed, indicating that ammonia has a presynaptic depressant effect on the IPSP. Ammonia also depressed excitatory postsynaptic potentials (EPSPs), presynaptic fiber potentials, and pyramidal cell population spikes. In addition, the calcium-dependent potassium response elicited by depolarizing current pulses was depressed. This depression was due, in part, to a depolarizing shift in the reversal potential for this response. Responses recorded with potassium-sensitive microelectrodes indicate that ammonia releases potassium into the extracellular space. The possibility is discussed that the shifts in IPSP reversal potential seen with high concentrations of ammonia are a consequence of generalized nonspecific effects. We conclude that the relative insensitivity of hippocampal IPSPs to blockade by ammonia suggests that a mechanism fundamentally unlike an ammonia-sensitive chloride pump must maintain the hippocampal IPSP gradient.

Action Potentials↗

PubMed1984

Electrophysiology of dentate gyrus granule cells.

The orthodromic synaptic responses, membrane properties, and responses of dentate gyrus granule cells (DGCs) to several convulsant agents were studied in the in vitro hippocampal slice preparation. Orthodromic stimulation via the perforant pathway (PP) evoked excitatory-inhibitory postsynaptic potentials (EPSP-IPSP) sequences in 27 of 34 DGCs studied. In the majority, only one action potential could be evoked by supramaximal orthodromic stimulation. In recordings from DGC somata, overshooting spikes could be evoked either orthodromically or by current injections. Small-amplitude, fast transients were seen in 5 of 34 DGCs. The current/voltage (I-V) characteristic of most DGCs was linear throughout a range of membrane potentials between 15 and 20 mV negative and 5 and 15 mV positive to the resting potential. At the extremes of this range nonohmic behavior was noted. Exposure of slices to agents that block IPSPs, such as penicillin, bicuculline, picrotoxin, and media containing low Cl- concentrations, eliminated PP-evoked hyperpolarizations in DGCs and prolonged the repolarizing phase of the PP EPSP. In contrast to findings in hippocampal pyramidal cells and neocortical neurons, blockade of IPSPs did not lead to the development of orthodromically evoked slow depolarizations and burst discharges. After slices were exposed to 5 mM tetraethylammonium, current pulses evoked slow spikes, which were resistant to tetrodotoxin and presumably mediated by Ca2+. Spontaneous burst discharges or bursts evoked by brief depolarizing pulses did not occur under these conditions. Substitution of Ba2+ for Ca2+ in the perfusion solution resulted in development of spontaneous slow membrane depolarizations and burst discharges in DGCs. Burst discharges could be directly evoked and spikes were prolonged and resistant to tetrodotoxin (TTX). After hyperpolarizations lasting 200-1,000 ms, associated with a conductance increase and presumably due to a Ca2+-activated K+ conductance, followed directly evoked spike trains in 5 of 20 DGCs. These data suggest that Ca2+ conductances may be evoked in DGCs under certain circumstances but are not prominent during activation of DGCs under standard in vitro recording conditions.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

PubMed1984

Electrophysiology of neurons of lateral thalamic nuclei in cat: mechanisms of long-lasting hyperpolarizations.

Intracellular recordings were performed in the lateral thalamic nuclei of cats under barbiturate anesthesia. The nature of cyclic hyperpolarizations triggered in relay cells by cortical stimulation was analyzed. These long-lasting hyperpolarizations were made of three different components. The early component, which was reversed by current and Cl injections, was identified as a Cl-dependent inhibitory postsynaptic potential (IPSP). A depolarizing hump was usually present in the depth of the long-lasting hyperpolarization. This intermediate component was identified as a voltage-dependent dendritic Ca conductance on the basis of recordings and ethylene glycol tetraacetic acid (EGTA) injections performed in relay cell dendrites. The late phase of hyperpolarization was dissociated from the early IPSP by its differential sensitivity to current and Cl injections and to conditioning tetanic stimulation. This late component was abolished by EGTA and, thus, was interpreted as a Ca-dependent K conductance increase. Activation of intrinsic somatic or dendritic conductances by current pulses never generated rhythmic hyperpolarizations in thalamic relay neurons. Oscillations appear to be imposed on these cells by synaptic inputs. It is then proposed that other thalamic neurons would have pacemaker properties and/or that oscillations would be produced in thalamic cellular pools by feedback interconnections.

Animals↗

PubMed1985

Use-dependent depression of IPSPs in rat hippocampal pyramidal cells in vitro.

We have used intracellular recording techniques to study the use-dependence of evoked inhibitory postsynaptic potentials (IPSPs) in rat CA1 hippocampal pyramidal cells. We determined reversal potentials and conductance changes associated with IPSPs and responses to directly applied gamma-aminobutyric acid (GABA). The IPSP depression could be seen after a single conditioning stimulus. This depression appeared to be due primarily to a 50% decrease in IPSP conductance (gIPSP). Trains of stimulating pulses (50 pulses at 5 or 10 Hz) produced more pronounced effects than a single conditioning pulse. Suprathreshold repetitive stimulation of stratum radiatum (SR) produced epileptiform burst firing and greater depression of IPSPs than did alvear (ALV) or subthreshold SR stimulation. During suprathreshold SR stimulation the IPSP was nearly abolished and the membrane potential could become less negative than the resting potential. A masking effect of facilitated depolarizing potentials on IPSPs was unlikely since IPSPs accompanied by little or no depolarizing potential were also depressed by SR trains. The 75% reduction in IPSP conductance found after repetitive stimulation confirmed that an overlapping conductance was not responsible for the depression of the IPSP. The GABA-induced conductance increase was not depressed by identical trains. Trains of stimulation induced depolarizing shifts in equilibrium potentials for the IPSP (EIPSP) and GABA (EGABA) of approximately 10 mV. These shifts were always greater after SR trains than after ALV trains. Simultaneous recordings of membrane potential and extracellular potassium concentration ([K+]o) with K+-sensitive microelectrodes revealed a direct correlation between the two during a stimulus train. Membrane potential depolarized as much as 18 mV from the peak of the IPSP and [K+]o could increase to a maximum of 10 mM during some trains. A depressant effect (of approximately 50%) of K+ on IPSPs was demonstrated by brief pressure ejection of K+ near the soma. We conclude that repetitive stimulation depresses gIPSP and shifts EIPSP in the depolarizing direction. Whereas gIPSP began to decline after a single conditioning pulse, the additional depression of IPSPs produced by stimulus trains was due in large part to shifts in EIPSP. Depression of gIPSP was not due to desensitization or block of ionic conductances, since gGABA was not reduced. The EIPSP may change as a result of increases in [K+]o.

Animals↗

PubMed1985

Location of membrane conductance changes by analysis of the input impedance of neurons. II. Implementation.

Mathematical modeling has shown that it should be possible to determine the electrotonic location of membrane conductance changes in single neurons by analysis of the associated changes in the magnitude of the alternating-current (AC) input impedance. The form of the plot of change in the magnitude of the input impedance as a function of frequency (delta [Zn(f)]) should differ for changes in membrane conductance located at different electrotonic distances from the recording/current-injection site. Due to the axial resistance and the membrane capacitance, the higher frequencies are attenuated with distance to a greater degree than are the lower frequencies. Thus delta [Zn(f)] should drop to zero more rapidly with increasing frequency for distal than for proximal conductance changes. For distal changes in conductance, the sign of the change in the magnitude of the input impedance can even reverse in the higher frequency range, so that increases in conductance would produce increases in impedance. This effect may explain the paradoxical increases in impedance at 100 Hz reported for motor neuron inhibitory postsynaptic potentials. Sine-wave impedance measurements were made in single embryonic chick spinal neurons in tissue culture, and gamma-aminobutyric acid (GABA) was iontophoretically applied alternately to the soma and to a neurite at a measured distance from the soma. The impedance changes produced by the GABA-induced conductance changes were consistent with the expectations from the mathematical modeling, but the results suggest that the axial resistance of the neurites must be quite high in some cases. Distortions due to microelectrode capacitance and stray capacitances in the input stage of single-electrode bridge amplifiers can make sine-wave impedance measurements impossible. This difficulty was eliminated by modifications to the capacity compensation circuit of an active bridge amplifier. Noise and distortion of several other types can also introduce serious errors. Methods for minimizing such problems are discussed. In spite of its limitations, this method can be of great practical value, because it can give the electrotonic location of spontaneously occurring membrane conductance changes in single neurons even when unitary synaptic potentials cannot be resolved. These methods are currently being applied to hippocampal pyramidal cells in vivo to locate conductance changes during the electroencephalogram (EEG) theta-rhythm in rats. In such laminated structures, the determination of the anatomical source of a group of active synapses can be aided by location of the resultant membrane conductance changes.

Animals↗

PubMed1986

The effects of focal stimulation in nucleus raphe magnus and periaqueductal gray on intracellularly recorded neurons in spinal laminae I and II.

Single neurons in spinal laminae I and II of cats were recorded intracellularly while stimulating in nucleus raphe magnus (NRM) and periaqueductal gray (PAG) with monopolar tungsten microelectrodes. Brain stem stimulation inhibited about one-half of the nociceptive-specific neurons, whereas the other half was unaffected. Brain stem stimulation inhibited about one-half of the multireceptive neurons, but the other half was excited and then inhibited. Brain stem stimulation inhibited about one-third of the low-threshold neurons, one-half was excited then inhibited, and one-fifth showed no effect. In all classes of neurons, the inhibition was produced by an inhibitory postsynaptic potential (IPSP) that began with a latency of approximately 25 ms and lasted approximately 400 ms following a single stimulus. The IPSP occurred with a small conductance increase and was reversed by hyperpolarizing currents applied to the cell. These data indicate that NRM and PAG modulated laminae I and II neurons via a postsynaptic mechanism. The conduction velocity of this descending pathway was calculated to range from 6.1 to 66.6 m/s with an average of 13.8 m/s. These data also indicate heterogeneity in the pathway, since some neurons were inhibited, whereas other neurons were excited then inhibited by descending stimulation. Finally, these data indicate specificity in these descending pathways since nearly one-half of neurons that had low-threshold inputs were excited by brain stem stimulation, whereas nearly all nociceptive-specific neurons were either inhibited or unaffected.

Action Potentials↗

PubMed1987

Differential effects of tetanus toxin on inhibitory and excitatory synaptic transmission in mammalian spinal cord neurons in culture: a presynaptic locus of action for tetanus toxin.

Tetanus toxin reduces monosynaptic inhibitory and excitatory synaptic transmission in mouse spinal cord neurons in culture. Inhibitory transmission is preferentially reduced by the toxin; however, excitatory transmission is also ultimately reduced and blocked by the concentrations of toxin used in these studies. Recordings from monosynaptically connected cell pairs revealed a marked diminution in amplitude of evoked monosynaptic inhibitory postsynaptic potentials coincident with the onset of convulsant action at a time when evoked monosynaptic EPSPs were relatively unaffected. Increased polysynaptic excitation occurred as a result of diminished inhibition. This supports the reduction of inhibition as an important mechanism in the convulsant action of tetanus toxin. Quantal analysis of the late effects of tetanus toxin on the monosynaptic excitatory postsynaptic potential revealed a reduction in quantal number with no reduction in quantal size, thus demonstrating a presynaptic locus of action for the toxin on spinal neurons.

Animals↗

PubMed1987

Ia inhibitory interneurons and Renshaw cells as contributors to the spinal mechanisms of fictive locomotion.

The activity of selected single alpha-motoneurons, Renshaw cells (RCs), and Ia inhibitory interneurons (IaINs) during fictive locomotion was recorded via microelectrodes in decerebrate (precollicular-postmammillary) cats in which fictive locomotion was induced by stimulation of the mesencephalic locomotor region. The interrelationships in the timing and frequency of discharge among these three interconnected cell types were determined by comparing their averaged step cycle firing histograms, which were normalized in reference to motoneuron activity recorded in ventral root filaments. Previous findings that RCs are rhythmically active during locomotion and discharge in phase with the motoneurons from which they are excited were confirmed, and further details of the phase relationships between RC and alpha-motoneuron activity during fictive locomotion were obtained. Flexor and extensor RCs became active after the onset of flexor and extensor motoneuron activity, respectively. Maximal activity in extensor RCs occurred at the end of the extension phase coincidental with the onset of hyperpolarization and a decrease in activity in extensor motoneurons. Maximal flexor RC activity occurred during middle to late flexion and was temporally related to the onset of reduced flexor motoneuron activity. The IaINs recorded in the present experiments were rhythmically active during fictive locomotion, as previously reported. The quadriceps IaINs were mainly active during the extension phase of the step cycle, along with extensor RCs. Thus the known inhibition of quadriceps IaINs by RCs coupled to quadriceps and other extensor motoneurons is obviously not sufficient to interfere with the appropriate phasing of IaIN activity and reciprocal inhibition during fictive locomotion, as had been speculated. Most of the quadriceps IaINs analyzed exhibited a decrease in discharge frequency at the end of the extension phase of the step cycle, which was coincidental with increased rates of firing in extensor RCs. These data are consistent with the possibility that extensor RCs contribute to the reduction in quadriceps IaIN discharge at the end of the extension phase of the step cycle. The possibility that IaIN rhythmicity during fictive locomotion arises from periodic inhibition, possibly from Renshaw cells, was tested by stimulating the reciprocal inhibitory pathway throughout the fictive step cycle. The amplitude of Ia inhibitory postsynaptic potentials (IPSPs) varied significantly throughout the fictive step cycle in 14 of the 17 motoneurons tested, and, in 11 of these 14 motoneurons, the Ia IPSPs were maximal during the phase of the step cycle in which the motoneuron was most

Animals↗

PubMed1987

Sodium-potassium pump inhibitors increase neuronal excitability in the rat hippocampal slice: role of a Ca2+-dependent conductance.

We have used the rat hippocampal slice preparation as a model system for studying the epileptogenic consequences of a reduction in neuronal Na+-K+ pump activity. The cardiac glycosides (CGs) strophanthidin and dihydroouabain were used to inhibit the pump. These drugs had readily reversible effects, provided they were not applied for longer than 15-20 min. Hippocampal CA1 pyramidal cells were studied with intracellular recordings; population spike responses and changes in extracellular potassium concentration ([K+]o) were also measured in some experiments. This investigation focused on the possibility that intrinsic neuronal properties are affected by Na+-K+ pump inhibitors. The CGs altered the CA1 population response evoked by an orthodromic stimulus from a single spike to an epileptiform burst. Measurements of [K+]o showed that doses of CGs sufficient to cause bursting were associated with only minor (less than 1 mM) changes in resting [K+]o. However, the rate of K+ clearance from the extracellular space was moderately slowed, confirming that a decrease in pump activity had occurred. Intracellular recording indicated that CG application resulted in a small depolarization and apparent increase in resting input resistance of CA1 neurons. Although CGs caused a decrease in fast gamma-aminobutyric acid mediated inhibitory postsynaptic potentials (IPSPs), CGs could also enhance the latter part of the epileptiform burst induced by picrotoxin, an antagonist of these IPSPs. Since intrinsic Ca2+ conductances comprise a significant part of the burst, this suggested the possibility that Na+-K+ pump inhibitors affected an intrinsic neuronal conductance. CGs decreased the threshold for activation of Ca2+ spikes (recorded in TTX and TEA) without enhancing the spikes themselves, indicating that a voltage-dependent subthreshold conductance might be involved. The action of CGs on Ca2+ spike threshold could not be mimicked by increasing [K+]o up to 10 mM. A variety of K+ conductance antagonists, including TEA, 4-AP, Ba2+ (in zero Ca2+), and carbachol were ineffective in preventing the CG-induced threshold shift of the Ca2+ spike. The shift was also seen in the presence of a choline-substituted low Na+ saline. Enhancement of a slow inward Ca2+ current is a possible mechanism for the decrease in Ca2+ spike threshold; however, it is impossible to use the Ca2+ spike as an assay when testing the effects of blocking Ca2+ conductances. Therefore, we studied the influence of CGs on the membrane current-voltage (I-V) curve, since persistent voltage-dependent conductances appear as nonlinearities in the I-V plot obtained under current clamp.(ABSTRACT TRUNCATED AT 400 WORDS)

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