Journal of Neurophysiology

Uusitalo, R. O.; Juusola, M.; Kouvalainen, E.; Weckstrom, M.

doi: N/Apmid: 7472349

Abstract 1. We studied graded synaptic transmission in the fly photoreceptor-interneuron synapse by using intracellular in situ recordings from pre- and postsynaptic cells. 2. A large presynaptic hyperpolarization after light adaptation, caused by the activation of the electrogenic Na+/K+ pump, drastically reduced the conspicuous postsynaptic dark noise. At the same time, the postsynaptic neurons depolarized, with an increase of input resistance of 5-10 M omega. 3. The spectral characteristics of the postsynaptic membrane noise in dark and during noise reduction, together with the other results, suggested that the transmitter release decreased dramatically approximately 12 mV below the resting potential of the presynaptic photoreceptors. 4. During the postsynaptic noise reduction, the saturated and subsaturated first-order visual interneuron responses were increased up to 9 mV with a time constant of recovery of approximately 10 s. This increase was shown to be caused by the negative shift of the reversal potential of the transmitter-gated (mainly Cl-) conductance, caused apparently by the reduced transmitter input. 5. The results strongly suggest that the photoreceptor transmitter release in fly is tonic, even in dark, and further support the modulation of the synaptic voltage transfer by postsynaptic Cl- extrusion. Copyright © 1995 the American Physiological Society

Zhainazarov, A. B.; Ache, B. W.

doi: N/Apmid: 7472351

Abstract 1. Odor-evoked currents were recorded in Xenopus laevis olfactory receptor neurons (ORNs) by the use of conventional, as well as nystatin and gramicidin-perforated, whole cell recording. The odor-evoked current ran down quickly in conventional, but not in perforated, whole cell recording. All three types of recording gave similar values for the amplitude, latency, time-to-peak, recovery time, and reversal potential of the odor-evoked current. 2. A secondary Cl current comprised a significant part of the odor-evoked current (55-65%). ECl measured by gramicidin perforation, which does not alter Cl-i, was -2.3 +/- 5.0 (SE) mV, indicating that these neurons maintain a high Cl-i and that the secondary Cl current plays an excitatory role in olfactory transduction. Copyright © 1995 the American Physiological Society

Doze, V. A.; Cohen, G. A.; Madison, D. V.

doi: N/Apmid: 7472344

Abstract 1. Experiments were performed in rat hippocampal slices to examine the nature of GABAergic inhibition of inhibitory synaptic transmission. In these experiments the effects of the gamma-aminobutyric acid-B (GABAB) receptor agonist, baclofen, and of subtype-selective calcium channel blockers were tested with the use of intracellular recordings of evoked inhibitory postsynaptic potentials (IPSPs) and whole cell recordings of spontaneous GABAergic inhibitory postsynaptic currents (IPSCs). 2. Baclofen inhibited evoked and spontaneous (action-potential-dependent) monosynaptic GABAA-mediated IPSPs and IPSCs but had no effect on the frequency of tetrodotoxin-resistant (action-potential-independent) miniature IPSCs recorded in CA1 pyramidal neurons. 3. Depolarizing GABAergic synaptic terminals by raising the extracellular potassium concentration caused an increase in action-potential-independent miniature IPSC frequency that could be inhibited by either baclofen or cadmium, a blocker of voltage-dependent calcium channels. In addition, under these depolarizing conditions, cadmium occluded the baclofen inhibition of miniature IPSCs. These data suggest that baclofen reduces only depolarization-induced, not quantal, GABA release and that it does so by decreasing presynaptic voltage-dependent calcium influx. 4. Experiments with subtype-selective calcium channel blockers demonstrate that the presynaptic action of baclofen was mediated through both omega-conotoxin-GVIA-sensitive and omega-agatoxin-IVA-sensitive, but not dihydropyridine-sensitive calcium channels. Copyright © 1995 the American Physiological Society

Costa, A. M.; Spence, K. T.; Smith, S. S.; ffrench-Mullen, J. M.

doi: N/Apmid: 7472348

Abstract 1. The withdrawal properties of the endogenous steroid progesterone (P) were tested in female rats as a function of benzodiazepine modulation of gamma-aminobutyric acid-A (GABAA)-gated current with the use of the whole cell patch-clamp technique on acutely dissociated CA1 hippocampal neurons. In a previous study, this steroid was shown to exhibit withdrawal properties, behaviorally. 2. One day withdrawal from in vivo administration of physiological doses of P (5 mg ip, 5 days/wk for 3 withdrawal cycles) or its metabolite, the GABAA modulator 3 alpha-hydroxy-5 alpha-pregnan-20-one (3 alpha,5 alpha-THP or allopregnanolone, 20 mg/kg ip) prevented the normally potentiating effect of lorazepam (LZM; 10(-7)-10(-4) M) on GABAA-gated current. Withdrawal from 500 micrograms P administered concomitantly with 2 micrograms 17 beta-estradiol also markedly diminished LZM potentiation of GABAA current. This effect was seen only after three withdrawal cycles. 3. P withdrawal produced no inhibitory effect on either basal levels of GABAA-evoked current, the GABAA EC50, or barbiturate (+/-Pentobarbital, 10(-7)-10(-4) M) modulation of this parameter. 4. The effect of steroid withdrawal on LZM modulation of GABAA-evoked current was blocked by picrotoxin as well as by indomethacin, a drug that prevents conversion of P to its metabolite, the GABAA modulator 3 alpha,5 alpha-THP. These results suggest that the withdrawal properties of P may be due to changes in GABAA receptor function produced by 3 alpha,5 alpha-THP. Copyright © 1995 the American Physiological Society

Tsubokawa, H.; Oguro, K.; Masuzawa, T.; Nakaima, T.; Kawai, N.

doi: N/Apmid: 7472325

Abstract 1. We studied the effects of polyamine toxins derived from a spider venom on CA1 pyramidal neurons in gerbil hippocampal slices by patch-clamp recording. Joro spider toxin (JSTX) and its synthetic analogue, 1-naphthyl acetyl spermine (Naspm), which are known to block non-N-methyl-D-aspartate (non-NMDA) receptor in a subunit specific manner, were used. 2. Naspm depressed the excitatory postsynaptic currents (EPSCs) mediated by non-NMDA receptor channels. A further reduction of EPSCs occurred with addition of 6-cyano-7-nitroquin-oxaline-2,3- dione (CNQX). Conversely, when CNQX was applied first, no further depression of EPSCs occurred on addition of Naspm, indicating that Naspm blocks a fraction of the CNQX-sensitive non-NMDA-receptor-mediated currents. 3. After ischemia, the time course of EPSCs of CA1 pyramidal neurons was slowed and Naspm depressed the slow EPSCs more strongly than those in control neurons. 4. Analysis of single-channel currents by outside-out patch-clamp recording from ischemic CA1 neurons revealed that Naspm blocked a subpopulation of alpha-amino-3-hydroxy-5-methylisoxazole-4-propionate- and kainate-induced single-channel currents. 5. Because the EPSCs in CA1 neurons after ischemia are mediated by Ca(2+)-permeable non-NMDA receptor-mediated conductances, the present results indicate that Naspm and JSTX are effective at blocking abnormal EPSCs that may induce Ca2+ accumulation leading to delayed neuronal death after transient ischemic insult. Copyright © 1995 the American Physiological Society

Kanemasa, T.; Gan, L.; Perney, T. M.; Wang, L. Y.; Kaczmarek, L. K.

doi: N/Apmid: 7472324

Abstract 1. The Shaw-like voltage-activated potassium channel Kv3.1 is expressed in neurons that generate rapid trains of action potentials. By expressing this channel in a mammalian cell line and by simulating its activation, we tested the potential role of this channel in action potential repolarization. 2. NIH 3T3 fibroblasts were stably transfected with Kv3.1 DNA. Currents recorded in these cells had a threshold of activation at approximately -10 mV, showed little inactivation, and were very sensitive to blockade by 4-aminopyridine and tetraethylammonium. 3. Kv3.1 currents activated rapidly at the onset of depolarizing voltage pulses. After an initial rapid phase of activation, which could be fit by an n4 Hodgkin-Huxley model, Kv3.1 currents expressed in fibroblasts had a second, slower phase of activation, and, in some cells, a slower phase of partial inactivation, both of which could be fit with modified n4p models. 4. Cell-attached single-channel recordings indicated that the Kv3.1 channel displays two gating behaviors, a short-open-time pattern, which occurs only at the onset of depolarization, and a long-open-time pattern, which predominates during prolonged depolarizations. 5. The amplitude of Kv3.1 currents, and the probability of channel openings, was reduced by a phorbol ester activator of protein kinase C, and the action of this agent was blocked by preincubation with the protein kinase inhibitor H7 (1-5-isoquinolinesulfonyl-2-methyl piperazine). In contrast, the effects of dioctanoyl glycerol, which also attenuated the currents, could not be completely blocked by H7, suggesting that diacylglycerols may act on the channel by a kinase-independent pathway. 6. Incorporation of a current with the kinetics and voltage dependence of Kv3.1 currents into a model cell with a sustained inward current showed that, in contrast to other delayed-rectifier currents such as the Shaker-like Kv1.1 and Kv1.6 channels, the level of expression of Kv3.1 currents could be varied over a wide range without attenuation of action potential height. Our results suggest that the Kv3.1 channel may provide rapidly firing neurons with a high safety factor for impulse propagation. Copyright © 1995 the American Physiological Society

Kim, Y. I.; Chandler, S. H.

doi: N/Apmid: 7472335

Abstract 1. The responses of guinea pig trigeminal motoneurons (TMNs) to N-methyl-D,L-aspartate (NMA) were studied using brain stem slice preparations and whole cell patch-clamp (n = 89) or conventional microelectrode (n = 22) recording techniques. The primary goals of this study were to determine whether N-methyl-D-aspartate (NMDA) receptor activation would produce spontaneous bursting activity in TMNs and, if so, the underlying mechanisms responsible for the generation of these bursts. 2. Bath-applied NMA (100-300 microM, n = 80) in standard perfusion medium elicited depolarization, increase in apparent input resistance (Rinp), and rhythmic burst discharges (1-90 s in duration) from TMNs. These effects were blocked by the NMDA receptor antagonist DL-2-amino-5-phosphonopentanoic acid (AP5, 30 microM, n = 6), but not by the non-NMDA receptor antagonist 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX, 5-10 microM, n = 10). Furthermore, the burst-inducing effect of NMA was not mimicked by the non-NMDA receptor agonists kainate (KA, 5-10 microM, n = 6) and (+/-)-alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA, 5-10 microM, n = 5). 3. In tetrodotoxin (TTX) treatment conditions (n = 13), NMA elicited depolarization, an increase in apparent Rinp, and rhythmic membrane potential oscillations without action potential bursts (i.e., plateau potentials), suggesting that the effects of NMA observed in the TTX-free condition resulted from activation of postsynaptic NMDA receptors. 4. Graded depolarization of neurons (n = 20) by intracellular direct current injection generally led to a graded increase in frequency and duration of the NMA-induced bursts and plateau potentials until these rhythmic events eventually became transformed into continuous spike discharge and maintained depolarization, respectively. Removal of Mg2+ from the perfusion medium (n = 11) also turned the bursts and plateau potentials into continuous spike discharge and maintained depolarization, respectively. 5. The effects of NMA on the current-voltage (I-V) curve after a depolarizing ramp voltage-clamp command (15-20 mV/s) were examined (n = 40). Under NMA (100-300 microM) conditions, the I-V relationship exhibited a region of negative slope conductance (NSC) between -60 and -35 mV, thus making the I-V relationship N-shaped. The NSC was abolished by AP5 (30 microM, n = 8), but not by CNQX (5-10 microM, n = 6). The I-V relationship in AMPA (3-10 microM, n = 5) or KA (3-10 microM, n = 5) was almost linear between -80 and -30 mV.(ABSTRACT TRUNCATED AT 400 WORDS) Copyright © 1995 the American Physiological Society

Franowicz, M. N.; Barth, D. S.

doi: N/Apmid: 7472356

Abstract 1. Transient and steady-state (40 Hz) evoked potentials, as well as spontaneous and click-evoked gamma-band oscillations, were recorded from 15 lightly anesthetized rats using an 8 x 8 electrode epipial array covering auditory cortex and adjacent areas to determine and compare the spatiotemporal distributions of these four phenomena. 2. The transient evoked response replicated earlier findings in our laboratory, consisting of an initial biphasic sharp wave in area 41, a similar but delayed biphasic sharp wave in area 36, and more widely distributed slow-wave components. Spatiotemporal analysis supported a model of parallel and asynchronous activation of distinct groups of thalamocortical projections underlying the neurogenesis of these temporal components of the middle-latency auditory evoked potential (MAEP) complex. 3. The 40-Hz response to click trains was superimposed on a steady potential shift (SP), both of which were localized within primary auditory cortex. Epipial distributions of the SP were similar to those of the shortest-latency negative peak in area 41 recorded in the same animals, suggesting similar neural generators. The 40-Hz response was more focal and dissimilar from the SP and any other temporal components of the MAEP complex, suggesting that a unique subpopulation of cells underlies its neurogenesis. 4. Spontaneous gamma-band activity, as assessed by power spectrum analysis, was localized to primary and secondary auditory cortex but had a variable distribution between rats that did not conform to the cytoarchitectonic boundaries within subdivisions of this region. Digital movies computed for individual bursts of gamma-activity indicated a high degree of spatiotemporal variability within and between bursts. 5. Single-trial spectral analysis of click responses indicated an inhibition of gamma-band oscillations during most of the MAEP complex, with subsequent enhanced gamma-activity during the 300- to 350-ms slow-wave component that outlasted the MAEP by approximately 500 ms. The epipial distributions of prestimulus and enhanced poststimulus gamma-oscillations were the same. In contrast to the 40-Hz response to click trains, phase-locking of gamma-oscillations by the single click stimulus was not observed. 6. These results suggest that both the MAEP complex and the steady-state 40-Hz response with its associated SP are highly stereotyped in lightly anesthetized rodent cortex. Their spatiotemporal distributions are probably determined in large part by asynchronous activation of parallel thalamocortical projection systems. Our data suggest no direct link between either the MAEP or the steady-state 40-Hz response to spontaneous or evoked gamma-band oscillations in auditory cortex.(ABSTRACT TRUNCATED AT 400 WORDS) Copyright © 1995 the American Physiological Society

Cohen, M. I.; Yu, Q.; Huang, W. X.

doi: N/Apmid: 7472350

Abstract 1. In vagotomized, paralyzed, decerebrate cats, simultaneous recordings were taken from one or more sympathetic nerves cervical sympathetic (CS), inferior cardiac (IC), splanchnic (SP) and from medullary neurons in vasomotor-related regions. Coherence analyses were used to ascertain the presence of sympathetic rhythms (2-6 Hz or "3-Hz rhythm," 7-13 Hz or "10-Hz rhythm") that were correlated between different signals. The occurrence of a significant peak at such a frequency in a unit-nerve coherence spectrum allowed the identification of a medullary neuron as sympathetic related. 2. A serendipitous example is given of a rostral ventrolateral medullary neuron that had significant unit-nerve 10-Hz coherence peaks for three sympathetic nerves (CS, IC, SP); but, as revealed by partial coherence analysis, the unit activity's correlation with one nerve's activity could be partially or completely dependent on its correlation with other nerve activities. Thus in this case the unit-CS and unit-IC coherences at 10 Hz were completely dependent on the SP rhythm, whereas the unit-SP coherence was not significantly affected by the CS and IC rhythms. This asymmetry suggests that the neuron was preferentially connected to SP-generating medullary circuits. 3. This example indicates the strength of partial coherence analysis as a means of studying differential connectivity between medullary sympathetic-related neurons and sympathetic output neuron populations. Copyright © 1995 the American Physiological Society

Johnson, B. R.; Peck, J. H.; Harris-Warrick, R. M.

doi: N/Apmid: 7472345

Abstract 1. In the pyloric network of the lobster stomatogastric ganglion, graded synapses organize the network output. The amines dopamine (DA), serotonin, and octopamine each elicit a distinctive motor pattern from a quiescent pyloric network. We have examined the effects of these amines on the graded synaptic strengths between the six major types of neurons of this network to understand how amine modulation of synaptic strength contributes to the amine-induced motor patterns. Here we tested amine affects at 10 different graded chemical synapses of the pyloric network. We show that each amine has a statistically different spectrum of distributed effects across the network synapses. 2. Under our control conditions (isolated pairs of neurons, removal of modulatory input), most of the graded chemical synapses were weak and some synapses were nonfunctional. The output synapses of the ventricular dilator (VD) neuron were significantly stronger than the other synapses. 3. DA altered the synaptic strength of every graded chemical synapse. This amine strengthened the weak chemical output synapses of the anterior burster (AB), lateral pyloric (LP), and pyloric constrictor (PY) neurons and weakened (and in some cases abolished) the strong chemical output synapses of the VD neuron. The AB-->inferior cardiac neuron (IC) and PY-->IC graded chemical synapses were nonfunctional under our control conditions; DA activated these silent synapses. 4. Serotonin enhanced the AB's output chemical synapses but weakened all the other graded chemical synapses examined. Octopamine's effects were much weaker than those of the other two amines. It enhanced the AB-->LP synapse and the LP's output synapses and weakly strengthened the AB-->PY, VD-->LP, and VD-->PY synapses. 5. The amines alter the input resistance of many of the pyloric neurons, and this could contribute to the observed changes in synaptic strength by altering passive current flow between input and output sites in the cells. However, the input resistance changes were relatively small compared with the changes in synaptic strength and cannot alone account for the synaptic modulation. In some cases the sign of the input resistance change was inconsistent with the change in synaptic strength. Thus the amines appear to modify synaptic transmission directly in this system. 6. This study completes our description of amine effects on all the graded synapses of the pyloric network. We summarize our present and earlier work to show that modulators can reconfigure the entire synaptic organization of a neural network by acting at many distributed synaptic sites.(ABSTRACT TRUNCATED AT 400 WORDS) Copyright © 1995 the American Physiological Society