bluuebunny/crossref_metadata_2025 huggingface dataset:
Inhibitory postsynaptic currents and the effects of GABA on visually identified sacral parasympathetic preganglionic neurons in neonatal rats
Authors: Araki I.
Published: December 2017

1. The actions of gamma-aminobutyric acid (GABA) on sacral parasympathetic preganglionic (SPP) neurons were examined in slice preparations using the whole cell patch-clamp technique. 2. Inhibitory postsynaptic currents (IPSCs), which were evoked by focal electrical stimulation, were recorded from SPP neurons in the presence of 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX), a glutamate receptor antagonist. The IPSCs were substantially reduced by strychnine (1 microM), a glycine receptor antagonist. The remaining IPSCs were completely blocked by bicuculline (20 microM), a GABAA receptor antagonist. The mean peak amplitude of bicuculline-sensitive, GABAergic currents recorded at -60 mV was 53.6 +/- 10.9%, mean +/- SD (n = 8), of that of the total IPSCs. The GABAergic currents were reversed in polarity at about -30 mV, near the Cl- equilibrium potential. 3. GABA (5-50 microM) induced inward currents in SPP neurons with symmetrical internal and external Cl- concentrations. This response was completely blocked by 100 microM bicuculline. Muscimol (2-8 microM), a GABAA agonist, mimicked the GABA-induced responses, whereas a GABAB receptor agonist, baclofen (20-200 microM), produced responses in only a few cells. The GABA-induced currents reversed their polarity at approximately 0 mV, near the Cl- equilibrium potential. When the internal Cl- concentration was reduced, the reversal potential was shifted according to the Nernst equation for Cl-. 4. GABA-induced currents exhibited an outward "hump" between -35 and 15 mV. This voltage range coincided with that at which a depolarization-induced inward whole cell current was elicited.(ABSTRACT TRUNCATED AT 250 WORDS)
Dynamics of visually guided auditory plasticity in the optic tectum of the barn owl
Authors: Brainard M. S. , Knudsen E. I.
Published: December 2017

1. In the optic tectum of normal barn owls, bimodal (auditory-visual) neurons are tuned to the values of interaural time difference (ITD) that are produced by sounds at the locations of their visual receptive fields (VRFs). The auditory tuning of tectal neurons is actively guided by visual experience during development: in the tectum of adult owls reared with an optically displaced visual field, neurons are tuned to abnormal values of ITD that are close to the values produced by sounds at the locations of their optically displaced VRFs. In this study we investigated the dynamics of this experience-dependent plasticity. 2. Owls were raised from shortly after eye-opening (14-22 days of age) with prismatic spectacles that displaced the visual field to the right or left. Starting at approximately 60 days of age, multiunit recordings were made to assess the tuning of tectal neurons to ITD presented via earphones. In the earliest recording sessions (ages 60-80 days), ITD tuning was often close to normal, even though the majority of the owls' previous experience was with an altered correspondence between ITD values and VRF locations. Subsequently, over a period of weeks, responses to the normal range of ITDs were gradually eliminated while responses to values of ITD corresponding with the optically displaced VRF were acquired. 3. At intermediate stages in this process, the ITD tuning at many sites became abnormally broad, so that responses were simultaneously present to both normal values of ITD and to values corresponding with the optically displaced VRF. At this stage the latencies and durations of newly acquired responses systematically exceeded the latencies and durations of the responses to normal values of ITD. 4. Dynamic changes in ITD tuning similar to those recorded in the optic tectum also occurred in the external nucleus of the inferior colliculus (ICX), which provides the major source of ascending auditory input to the tectum. 5. These results suggest the hypothesis that the neural selectivity for ITD in the barn owl's tectum is first established by vision-independent mechanisms and only subsequently calibrated by visual experience. This calibration involves both the elimination of responses to normal values of ITD and the visually guided acquisition of responses to novel values and can be accounted for by plasticity at the level of the ICX.
In vitro brain slice studies of the rat's dorsal nucleus of the lateral lemniscus. I. Membrane and synaptic response properties
Authors: Wu S. H. , Kelly J. B.
Published: December 2017

1. We examined the physiological properties of neurons in the dorsal nucleus of the lateral lemniscus (DNLL) of the rat in a 400-microns tissue slice taken in the frontal plane through the auditory midbrain. The brain slice was placed in a small chamber and was perfused fully submerged in a warm, continuously circulating oxygenated saline solution. We made intracellular recordings with glass pipettes filled with 4 M potassium acetate. Synaptic potentials were evoked by electrical stimulation of either the lateral lemniscus or the commissure of Probst. 2. We tested the membrane characteristics of DNLL neurons by recording the electrical potentials produced by intracellular injection of positive or negative current. Typically, DNLL neurons had nearly linear current-voltage curves and responded to depolarizing currents with a sustained train of action potentials. Injection of intense or prolonged depolarizing currents frequently resulted in a pronounced afterhyperpolarization of the cell membrane. Intense hyperpolarizing currents were often followed by a large rebound depolarization. 3. The action potentials of most DNLL neurons were characterized by a double undershoot, i.e., the initial hyperpolarization after a spike was followed by a second, longer-latency hyperpolarization. Seventy-nine percent of the cells recorded had this type of double undershoot. The remaining cells had a single undershoot in which the postspike hyperpolarization was followed by a steady return to resting potential without any indication of a second phase of hyperpolarization. 4. Electrical stimulation of the lateral lemniscus evoked both excitatory postsynaptic potentials (EPSPs) and inhibitory postsynaptic potentials (IPSPs) in DNLL. The EPSPs were evoked alone without any evidence of an IPSP in 67% of neurons and IPSPs were evoked alone in 6% of the neurons from which recordings were made. In 27% of the recordings both EPSPs and IPSPs were elicited in the same neuron by stimulation of a single location on the lateral lemniscus. 5. The combined EPSPs and IPSPs produced by lemniscal stimulation could often be dissociated by their different thresholds and/or different response latencies. For 35% of the neurons in which both an EPSP and IPSP were present, the IPSP had a lower threshold; for 23% of the cells, the EPSP had a lower threshold. For the remaining cells the thresholds for producing an EPSP and IPSP were the same. 6. DNLL neurons were capable of responding with great fidelity to a single pulse of stimulation delivered to the lateral lemniscus, i.e., an action potential was evoked after every stimulus.(ABSTRACT TRUNCATED AT 400 WORDS)
Intracellular QX-314 blocks the hyperpolarization-activated inward current Iq in hippocampal CA1 pyramidal cells
Authors: Perkins K. L. , Wong R. K.
Published: December 2017

1. Whole cell voltage-clamp recordings (access resistance < or = 12 M omega) from CA1 pyramidal cells in the guinea pig hippocampal slice revealed a hyperpolarization-activated inward current with an inward tail upon repolarization. The current activation range extended from approximately -50 mV to -130 mV, with half-activation at -86 mV. This current was identified as the q current (Iq). 2. Intracellular QX-314 (5 or 10 mM), a quaternary derivative of lidocaine, blocked Iq completely throughout its activation range. 3. There is a growing realization that Iq may be responsible for the pacemaker depolarization in cells that display rhythmic calcium spikes. Because QX-314 blocks Iq completely, it could be used to test whether Iq is essential to this oscillatory activity.
Parallel processing of tactile information in cat cerebral cortex: effect of reversible inactivation of SII on SI responses
Authors: Turman A. B. , Morley J. W. , Zhang H. Q. , Rowe M. J.
Published: December 2017

1. Responsiveness of neurons in the distal forelimb region of primary somatosensory cortex (SI) was examined in cat in association with the cooling-induced, reversible inactivation of the corresponding region of the second somatosensory area (SII). The aim was to test whether a component of the stimulus-generated tactile input to SI came via an indirect, intracortical path from the thalamus through SII, or whether, when SI responsiveness fell in association with SII inactivation, the effect could be explained by a disfacilitation of the SI neuron; that is, a removal of a tonic facilitatory influence on the SI neuron that arises from within SII. 2. The responses of 33 SI neurons to controlled tactile stimuli, usually 1-s long trains of vibration or rectangular pulses delivered to the skin of the distal forelimb, were examined quantitatively before, during, and after the rapid, reversible inactivation of the SII area. 3. Nineteen of the 33 neurons (approximately 60%) were unaffected in their response level by SII inactivation. These included neurons of several functional classes whose input came from different classes of tactile afferent fibers, including the Pacinian corpuscle (PC) associated fibers, other rapidly adapting (RA) afferents from glabrous skin, and presumed hair follicle afferent (HFA) fibers. The remaining 14 neurons (approximately 40%), which also included different functional classes, displayed a reduction in response level with SII inactivation. Because this was not accompanied by significant prolongation of the SI spike waveforms, it is not attributable to direct spread of cooling from SII to SI. Construction of stimulus-response relations demonstrated that any effect of SII inactivation on individual SI neurons was consistent over the whole response range. 4. The fall in responsiveness for some SI neurons in association with SII inactivation may be attributable to disfacilitation, that is, a loss of tonic facilitation arising in SII, rather than to a block of peripherally generated inputs that traverse an indirect path from the skin to SI, via SII. There are three reasons for suggesting this. First, in the course of SII cooling, the latency and time course of SI evoked potentials were not delayed in a way that might be expected if part of the SI response had come via SII. Second, the SII inactivation could reduce the SI spontaneous activity (as well as the stimulus-related responsiveness). The facilitation from SII is therefore not necessarily dependent on overt tactile stimulation, and its source may therefore be endogenous to SII.(ABSTRACT TRUNCATED AT 400 WORDS)
Presynaptic inhibition by serotonin of glycinergic inhibitory synaptic currents in the rat brain stem
Authors: Umemiya M. , Berger A. J.
Published: December 2017

1. With the use of a thin brain stem slice preparation, we recorded in visualized neonatal rat hypoglossal motoneurons unitary glycinergic inhibitory postsynaptic currents (IPSCs) that were evoked by extracellular stimulation of nearby interneurons. We found that 10 microM serotonin (5-HT) presynaptically inhibited this glycinergic synaptic transmission by 85.5%. 2. In the somata of presynaptic interneurons, 5-HT1A receptor activation potentiated inwardly rectifying K+ channels and inhibited voltage-activated calcium channels. 3. In contrast, the 5-HT1B receptor was primarily responsible for inhibition of evoked glycinergic IPSCs; a selective 5-HT1B receptor agonist, N-(3-trifluoromethylphenyl)piperazine (TFMPP, 10 microM), inhibited synaptic transmission by 97.3%. On the other hand, 5-HT1A receptor activation by (+)-8-OH-dipropylaminotetralin (8-OHDPAT, 1 microM) inhibited IPSCs by only 24.1%. A 5-HT1A antagonist, 1-(2-methyoxyphenyl)-4-[4-(2-phthalimido)-butyl]piperazine hydrobromide (NAN-190, 1 microM), had no effect on synaptic inhibition by 5-HT. 4. In the presence of tetrodotoxin (TTX) as well as TTX with cadmium (50 microM), we found that 5-HT1B receptor activation by TFMPP reduced the frequency of spontaneous miniature IPSCs (mIPSCs) without changing their mean amplitude. The results suggested that the 5-HT1B receptors activated at the presynaptic terminal inhibited synaptic transmission independent of inhibiting calcium influx through voltage-activated calcium channels. 5. These results indicate that activation of inwardly rectifying K+ channels and inhibition of voltage-activated calcium channels by 5-HT1A receptor activation do not constitute a main pathway for presynaptic inhibition by 5-HT of glycinergic synaptic transmission.(ABSTRACT TRUNCATED AT 250 WORDS)
Hair-cell counts and afferent innervation patterns in the cristae ampullares of the squirrel monkey with a comparison to the chinchilla
Authors: Fernandez C. , Lysakowski A. , Goldberg J. M.
Published: December 2017

1. The numbers of type I and type II hair cells were estimated by dissector techniques applied to semithin, stained sections of the horizontal, superior, and posterior cristae in the squirrel monkey and the chinchilla. 2. The crista in each species was divided into concentrically arranged central, intermediate, and peripheral zones of equal areas. The three zones can be distinguished by the sizes of individual hair cells and calyx endings, by the density of hair cells, and by the relative frequency of calyx endings innervating single or multiple type I hair cells. 3. In the monkey crista, type I hair cells outnumber type II hair cells by a ratio of almost 3:1. The ratio decreases from 4-5:1 in the central and intermediate zones to under 2:1 in the peripheral zone. For the chinchilla, the ratio is near 1:1 for the entire crista and decreases only slightly between the central and peripheral zones. 4. Nerve fibers supplying the cristae in the squirrel monkey were labeled by extracellular injections of horseradish peroxidase (HRP) into the vestibular nerve. Peripheral terminations of individual fibers were reconstructed and related to the zones of the cristae they innervated and to the sizes of their parent axons. Results were similar for the horizontal, superior, and posterior cristae. 5. Axons seldom bifurcate below the neuroepithelium. Most fibers begin branching shortly after crossing the basement membrane. Their terminal arbors are compact, usually extending no more than 50-100 microns from the parent exon. A small number of long intraepithelial fibers enter the intermediate and peripheral zones of the cristae near its base, then run unbranched for long distances through the neuroepithelium to reach the central zone. 6. There are three classes of afferent fibers innervating the monkey crista. Calyx fibers terminate exclusively on type I hair cells, and bouton fibers end only on type II hair cells. Dimorphic fibers provide a mixed innervation, including calyx endings to type I hair cells and bouton endings to type II hair cells. Long intraepithelial fibers are calyx and dimorphic units, whose terminal fields are similar to those of other fibers. The central zone is innervated by calyx and dimorphic fibers; the peripheral zone, by bouton and dimorphic fibers; and the intermediate zone, by all three kinds of fibers. Internal (axon) diameters are largest for calyx fibers and smallest for bouton fibers. Of the entire sample of 286 labeled fibers, 52% were dimorphic units, 40% were calyx units, and 8% were bouton units.(ABSTRACT TRUNCATED AT 400 WORDS)
Physiology and pharmacology of unitary synaptic connections between pairs of cells in areas CA3 and CA1 of rat hippocampal slice cultures
Authors: Debanne D. , Guerineau N. C. , Gahwiler B. H. , Thompson S. M.
Published: December 2017

1. Paired intracellular recordings were made in rat hippocampal slice cultures, with the use of either sharp microelectrodes or the whole cell configuration of the patch-clamp technique. Unitary synaptic connections were studied between pyramidal and nonpyramidal cells within and between areas CA1 and CA3. 2. Monosynaptic excitatory synaptic responses between CA3 pyramidal neurons were found in 56% of cell pairs (n = 91, 28 postsynaptic cells). Monosynaptic connections from a CA3 cell to a CA1 cell were observed in 76% of cell pairs (n = 125, 26 postsynaptic cells), but from CA1 to CA3 neurons in only 8% of cell pairs (n = 13, 13 postsynaptic cells). Monosynaptic excitatory connections were found in only 16% of CA1/CA1 cell pairs (n = 25, 10 postsynaptic cells). 3. Disynaptic inhibition was commonly observed between CA3 cell pairs (43%), but rarely found between CA3-CA1 pyramidal cell pairs (2%). In 50% of CA3 pyramidal cell pairs, synchronous inhibitory postsynaptic potentials (IPSPs) in both cells could be triggered by an action potential in one pyramidal cell. Reciprocal monosynaptic connections were found between 75% of interneuron and pyramidal cell pairs within area CA3. 4. The latency of monosynaptic CA3- to CA1-cell responses was significantly longer than for responses between two CA3 cells. Within area CA3 the latencies for inhibitory synaptic responses between interneurons and pyramidal cells were significantly shorter than those for excitatory responses between pyramidal cells. Monosynaptic excitatory postsynaptic potentials (EPSPs) in interneurons had a significantly shorter time-to-peak than those recorded in pyramidal neurons. 5. 6-Cyano-7-nitroquinoxaline-2,3-dione (CNQX)- and D-2-amino-5-phosphonovalerate (AP5)-sensitive components were identified in unitary monosynaptic EPSPs in CA3-CA3 and CA3-CA1 pyramidal cell pairs. The CNQX-sensitive component had a mean time-to-peak and duration of 6.2 +/- 0.3 (SE) ms and 61.2 +/- 2.0 ms, respectively, and an amplitude of approximately 1 mV (n = 93). The AP5-sensitive component of EPSPs was only detected when the cell was depolarized with respect to the resting potential, had a mean time-to-peak of 41 +/- 5 ms and duration of 121 +/- 11 ms (n = 6), and increased in amplitude with postsynaptic depolarization. 6. Unitary monosynaptic IPSPs between an interneuron and a pyramidal cell had a mean amplitude of approximately 1 mV and were fully blocked by gamma-aminobutyric acid-A (GABAA) receptor antagonists (n = 3). 7. Unitary inhibitory responses were found only within, but not between, areas CA3 or CA1.(ABSTRACT TRUNCATED AT 400 WORDS)
Modulation of an inhibitory interneuron in the neural circuitry for the tail withdrawal reflex of Aplysia
Authors: Xu Y. , Pieroni J. P. , Cleary L. J. , Byrne J. H.
Published: December 2017

1. Serotonin (5-HT), small cardioactive peptide B (SCPB) and FMRFamide have well-established facilitatory and inhibitory effects on sensory neurons and their connections with motor neurons mediating withdrawal reflexes in Aplysia. Little is known, however, about their effects on interneurons contributing to those reflexes. As a first step, we examined the effects of these three transmitters on the identified inhibitory interneuron RP14 in isolated pleural-pedal ganglia. 2. Bath application of 5-HT hyperpolarized RP14, inhibited its spontaneous activity and decreased its excitability. In addition, 5-HT decreased the amplitude of inhibitory postsynaptic potentials produced by RP14 in tail sensory and motor neurons. 3. In contrast, bath application of SCPB increased spontaneous activity in RP14. Subsequent application of 5-HT to the bath, which still contained SCPB, inhibited RP14. Therefore, the effects of SCPB were essentially opposite to those of 5-HT on this inhibitory interneuron. 4. FMRFamide had little effect on RP14. It did not produce an obvious change in its resting membrane potential and produced only a transient increase in its spontaneous activity. 5. These results suggest that various neuromodulators have differential effects on elements of the neuronal circuit underlying the tail-withdrawal reflex of Aplysia. Differential modulation may determine the overall behavioral manifestations associated with sensitization.
Regulation of the segmental swim-generating system by a pair of identified interneurons in the leech head ganglion
Authors: Brodfuehrer P. D. , Parker H. J. , Burns A. , Berg M.
Published: December 2017

1. The aim of this study was to identify neurons that modulate activity of segmental swim gating interneurons. We found a pair of bilaterally symmetrical interneurons, cells SE1, whose activity level directly influences three groups of segmental neurons associated with generating swimming in the medicinal leech. 2. The somata of cells SE1 are located on the dorsal surface of the subesophageal ganglion. Their axons extend most, if not the entire, length of the ventral nerve cord and appear to make identical connections with the same group of swim-generating neurons in all segmental ganglia. 3. Cells SE1 excite monosynaptically all segmental swim gating interneurons, cells 204, examined. The level of excitation in cell 204 is directly correlated with the firing frequency of cell SE1. In most quiescent preparations (when the preparation is not swimming) hyperpolarization of a single cell SE1 eliminates all excitatory synaptic input to cells 204. 4. Cells SE1 excite monosynaptically three swim oscillatory interneurons, cells 115, 28, and 208. The strength of the connection from cell SE1 to cell 115 is stronger than the connection from cell SE1 to either cells 28 or 208. The level of excitation in cell 115 is directly correlated with the firing frequency of cell SE1. In most quiescent preparations, hyperpolarization of a single cell SE1 eliminates all excitatory synaptic input to cell 115 but has only a minor effect on the level of activity in cells 208 and 28. 5. Due most likely to the strong and direct connections cells SE1 have with swim gating and oscillatory interneurons, brief stimulation of cell SE1 can elicit swimming. Swimming generally occurs within 1 s after stimulation of cell SE1. During swimming, the membrane potential of cell SE1 depolarizes by 2-5 mV, and its firing frequency increases. Brief depolarization of cell SE1 during swimming reliably shifts the phase of the swimming rhythm, whereas longer periods of depolarization increase both swim period and burst duration. 6. Excitatory motor neurons to the dorsal longitudinal muscles, cells 3, 5, and 7, are strongly excited by stimulation of cell SE1. The firing frequency of cell 3 is positively correlated with the firing frequency of cell SE1. 7. The results of this study indicate that cells SE1 can modulate the level of excitation in three groups of neurons associated with generating leech swimming.(ABSTRACT TRUNCATED AT 400 WORDS)
Ca(2+)-activated K current in the ARC muscle of Aplysia
Authors: Brezina V. , Weiss K. R.
Published: December 2017

1. This work continues our examination of the electrophysiology and contractions of single, functionally intact fibers dissociated from a widely studied molluscan muscle, the accessory radula closer (ARC) muscle of Aplysia californica, aimed at understanding its excitation-contraction mechanisms and their modulation. Extensive previous work has characterized a number of ion currents in the fibers. 2. Here we describe an additional major current that could not be studied earlier because, unlike all of the other currents in the ARC muscle fibers, it becomes prominent only during contraction of the fiber. It is a Ca(2+)-activated K current, associated with contraction most likely because both are activated by the same elevation in intracellular free Ca2+. 3. We used several manipulations to elicit the Ca(2+)-activated K current and contraction: depolarizing voltage steps in the presence of extracellular Ca2+, application of caffeine in the presence or absence of extracellular Ca2+ (and thus presumably working by releasing Ca2+ from intracellular stores), application of the Ca(2+)-ionophore A23187, and direct iontophoretic injection of Ca2+ into the fiber. 4. The Ca(2+)-activated K current reversed around -70 mV, not far from EK, and the reversal potential shifted substantially with elevated extracellular K+. Activation of the current was not only Ca2+ dependent, but also quite strongly voltage dependent, promoted by depolarization. The current was well blocked by tetraethylammonium (KD approximately 2 mM), but not blocked by even 10 mM 4-aminopyridine or low concentrations of the K-current blocking toxins charybdotoxin and apamin. 5. After a depolarizing voltage step in Ca(2+)-containing solution, the Ca(2+)-activated K current appeared, often with some delay, as a large peak of current that soon disintegrated into a prolonged period of individual oscillatory transients of Ca(2+)-activated K current, sometimes correlated with transient contractions. Similar transients could be elicited by caffeine or iontophoretic Ca2+ injection. More extensive study of the underlying Ca2+ dynamics will be presented elsewhere, but we interpret these phenomena in terms of our hypothesis that the ARC muscle generates both contraction and the Ca(2+)-activated K current by Ca(2+)-induced Ca2+ release (CICR), in which a small depolarization-induced influx of extracellular Ca2+ releases more Ca2+ from intracellular stores. 6. The Ca(2+)-activated K current is significant in the physiological operating voltage range of the ARC muscle, and its predicted hyperpolarizing action and consequent negative-feedback depression of contractions is likely to be an important part of the integrated set of mechanisms that regulate the muscle's contractility.
Responses of monkey inferior temporal neurons to luminance-, motion-, and texture-defined gratings
Authors: Sary G. , Vogels R. , Kovacs G. , Orban G. A.
Published: December 2017

1. We recorded from neurons responsive to gratings in the inferior temporal (IT) cortices of macaque monkeys. One of the monkeys performed an orientation discrimination task; the other maintained fixation during stimulus presentation. Stimuli consisted of gratings based on discontinuities in luminance, relative motion, and texture. 2. IT cells responded well to gratings defined solely by relative motion, implying either direct or indirect motion input into IT, an area that is part of the ventral visual cortical pathway. 3. Response strength in general did not depend on the cue used to define the gratings. Latency values observed for the two static grating types (luminance- and texture-defined gratings) were similar, but significantly shorter than those measured for the kinetic gratings. 4. Stimulus orientation had a significant effect in 27%, 27%, and 9% of the cells tested with luminance-, kinetic-, and texture-defined gratings, respectively. 5. Only a small proportion of cells were orientation sensitive for more than one defining cue. The average preferred orientation for luminance and kinetic gratings matched; the tuning width was similar for the two cues. 6. Our results indicate that IT cells may contribute to cue-invariant coding of boundaries and edges. We discuss the relevance of these results to visual perception.
Characterization of pharmacologically identified voltage-gated calcium channel currents in acutely isolated rat neocortical neurons. I. Adult neurons
Authors: Lorenzon N. M. , Foehring R. C.
Published: December 2017

1. Whole cell recordings were obtained from pyramidal neurons acutely dissociated from the sensorimotor cortex of adult rats. 2. Whole cell calcium channel currents were similar in appearance when elicited from holding potentials of -90 or -40 mV. With 5 mM Ba2+ as the charge carrier, currents began to activate at approximately -45 mV, peaked at approximately -10 mV, and had an apparent reversal potential of approximately +45 mV. Current amplitude and voltage dependence varied with the concentration and identity of the charge carrier (Ca2+ vs. Ba2+). Calcium channel currents were blocked completely by > 200 microM Cd2+ (IC50 approximately 3.5 microM). 3. We determined saturating doses for blockade of currents by nifedipine (Nif), omega-conotoxin GVIA (CgTx), and omega-agatoxin IVA (AgTx) in adult cells. We also tested the selectivity of these compounds by applying them in combination and in different orders. We found the three compounds to be highly, but not perfectly, specific. 4. L-type current was operationally defined as that blocked by 5 microM Nif, N-type current as that blocked by 1 microM CgTx, and P-type current as that blocked by 100 nM AgTx. In adult cells, each of these compounds blocked 30-35% of the current. When all three blockers were applied concurrently, approximately 80% of the current was blocked (20% of current was resistant to the 3 blockers). 5. Few biophysical differences were found between the pharmacologically defined current components in adult cells. The resistant current had a more rapid time-to-peak, inactivated more rapidly and completely, and activated at more negative potentials than the other three types.
Characterization of pharmacologically identified voltage-gated calcium channel currents in acutely isolated rat neocortical neurons. II. Postnatal development
Authors: Lorenzon N. M. , Foehring R. C.
Published: December 2017

1. Whole cell recordings were obtained from pyramidal neurons acutely dissociated from the sensorimotor cortex of adult (from Lorenzon and Foehring, companion paper) and immature rats postnatal day 1 (P1) to adult. 2. Whole cell calcium channel currents were similar in appearance at all ages. Current amplitudes and estimated densities were initially low (approximately 16 pA/pF at ages < P6) and increased gradually, attaining adult values at approximately 4-5 wk postnatally (approximately 100 pA/pF). 3. L-type current was operationally defined as that blocked by 5 microM nifedipine, N-type current as that blocked by 1 microM omega-conotoxin GVIA, and P-type current as that blocked by 100 nM omega-agatoxin IVA. A resistant current remained in the presence of the combination of these three blockers. The proportions of these four current types did not change during ontogeny. 4. Few biophysical differences were found between the pharmacologically defined current components in adult or 1-wk-old cells. At both ages the resistant current had a more rapid time-to-peak and inactivated more completely and rapidly than the other three types. Resistant currents also activated at more negative potentials. N-, L-, and P-type currents activated at more positive potentials in 1-wk-old cells than in adult cells. For the resistant current, the voltage dependence of activation was not significantly different between the two ages.
Laminar pattern of synaptic inhibition during convulsive activity induced by 4-aminopyridine in neocortical slices
Authors: Barkai E. , Friedman A. , Grossman Y. , Gutnick M. J.
Published: December 2017

1. Epileptiform activity was induced in rat neocortical brain slices by application of a low concentration (10 microM) of 4-aminopyridine (4-AP). In intracellular recordings from regular spiking neurons, the activity was characterized by prolonged, all-or-none depolarizing events, with variable delay to a threshold stimulus. 2. At this concentration, 4-AP had no measurable effect on passive electrical properties or on action-potential characteristics. 3. Paroxysmal responses in neurons of deeper layers differed markedly from those of superficial cells. In deep neurons, responses resembled those generated by neocortical neurons exposed to GABAergic blockers. A low-intensity stimulus to the white matter evoked an excitatory postsynaptic potential (EPSP) that was followed with variable latency by a paroxysmal depolarizing shift that reversed at suprathreshold membrane potentials and upon which superimposed repetitive firing was always evident. By contrast, in superficial (layer II-III) neurons, the same stimulus evoked an EPSP that was followed by a prolonged response whose late component reversed at subthreshold membrane potentials (between -50 and -80 mV). These cells rarely fired more than a single spike throughout the response. 4. Repetitive stimulation at relatively low frequencies (0.3-1 Hz) caused a gradual change in the synchronized responses that was most marked in superficial neurons. The reversal potential of the response shifted toward suprathreshold membrane potentials, and subsequently, superimposed repetitive firing became evident. These changes were not associated with measurable changes in input resistance or membrane potential.(ABSTRACT TRUNCATED AT 250 WORDS)
Structural and functional differences distinguish principal from nonprincipal cells in the guinea pig MSO slice
Authors: Smith P. H.
Published: December 2017

1. Principal cells in the medial superior olive (MSO) receive low-frequency information from both ears via left and right cochlear nuclei. In vivo extracellular records suggest that some MSO neurons respond optimally only when the binaural acoustic signal has a precise interaural delay. Thus MSO cells, in particular principal cells, are thought to be the first stage in the processing of interaural time difference cues that provides information as to the location of a low-frequency sound in space. 2. Despite this proposed fundamental role for the MSO, certain features of this nucleus make in vivo recordings from any cell type here very difficult to obtain. Only a small number of extracellular records and no intracellular recordings are reported in the literature. Using sharp, neurobiotin-filled glass electrodes to record intracellularly from cells in an in vitro brain slice of the guinea pig superior olivary complex, I have begun to assess the anatomic and physiological features of cells in the MSO that might be relevant to such a functional role in vivo. 3. Two basic MSO cell types, designated principal and nonprincipal, could be distinguished on the basis of certain anatomic and physiological differences. 4. Labeled principal cell bodies were located at all dorsoventral location within the MSO. Labeled nonprincipal cells were located in or around the dorsal aspects of the nucleus. Principal cells typically had thick bipolar dendrites (1 directed medially, 1 laterally) that did not taper or branch significantly except at their terminations. Nonprincipal cells were multipolar with three to nine thinner primary dendrites that did not branch preferentially in a mediolateral direction. Principal cell axons gave off collaterals terminating in and around the dorsal MSO. Nonprincipal cells also had axon in and around the dorsal MSO. Nonprincipal cells also had axon collateral branches innervating dorsal MSO, but these axons could branch more extensively and project further down the dorsoventral aspect of the nucleus. 5. Principal cells typically responded to depolarizing current pulses with one or a few spikes at current onset. When bathed in saline containing 4-aminopyridine (4-AP), they fired repetitively to the same depolarizing current pulses. This would indicate a depolarization-induced nonlinearity similar to that seen in principal cell types of two other auditory brain stem nuclei, the anteroventral cochlear nucleus and medial nucleus of the trapezoid body. Nonprincipal cells normally fired repetitively to depolarizing current pulses even close to spike threshold. Both cell types could show a sag in the membrane potential to hyperpolarizing current pulses.(ABSTRACT TRUNCATED AT 400 WORDS)
Dentate EEG spikes and associated interneuronal population bursts in the hippocampal hilar region of the rat
Authors: Bragin A. , Jando G. , Nadasdy Z. , van Landeghem M. , Buzsaki G.
Published: December 2017

1. This paper describes two novel population patterns in the dentate gyrus of the awake rat, termed type 1 and type 2 dentate spikes (DS1, DS2). Their cellular generation and spatial distribution were examined by simultaneous recording of field potentials and unit activity using multiple-site silicon probes and wire electrode arrays. 2. Dentate spikes were large amplitude (2-4 mV), short duration (< 30 ms) field potentials that occurred sparsely during behavioral immobility and slow-wave sleep. Current-source density analysis revealed large sinks in the outer (DS1) and middle (DS2) thirds of the dentate molecular layer, respectively. DS1 and DS2 had similar longitudinal, lateral, and interhemispheric synchrony. 3. Dentate spikes invariably were coupled to synchronous population bursts of putative hilar interneurons. CA3 pyramidal cells, on the other hand were suppressed during dentate spikes. 4. After bilateral removal of the entorhinal cortex, dentate spikes disappeared, whereas sharp wave-associated bursts, reflecting synchronous discharge of the CA3-CA1 network, increased several fold. 5. These physiological characteristics of the dentate spikes suggest that they are triggered by a population burst of layer II stellate cells of the lateral (DS1) and medial (DS2) entorhinal cortex. 6. We suggest that dentate spike-associated synchronized bursts of hilar-region interneurons provide a suppressive effect on the excitability of the CA3-CA1 network in the intact brain.
Recurrent spontaneous seizure activity in hippocampal neuronal networks in culture
Authors: Sombati S. , Delorenzo R. J.
Published: December 2017

1. Experiments were carried out using intracellular recording techniques on hippocampal neurons maintained in culture to determine if populations of hippocampal neurons could be induced to develop spontaneously recurring epileptiform discharges. This study demonstrates the conversion of normal hippocampal neurons in culture by a brief Mg(2+)-free treatment into a preparation of cells that permanently manifested recurrent, spontaneous seizure discharges. These electrographic seizure discharges illustrated the same electrographic properties seen in human epilepsy and were observed for the life of the culture. 2. The epileptic activity was shown to occur synchronously in populations of neurons and to be controlled by clinically useful anticonvulsant drugs. 3. This new cell culture model of epileptic activity provides a powerful tool to investigate the molecular mechanisms underlying the induction, maintenance, and termination of this "epileptic condition" in vitro and demonstrates that neuronal networks in culture can be transformed to manifest permanently spontaneous recurrent electrographic seizures.
Graded responses and spiking properties of identified first-order visual interneurons of the fly compound eye
Authors: Uusitalo R. O. , Juusola M. , Weckstrom M.
Published: December 2017

1. We studied the graded and spiking properties of the "non-spiking" first-order visual interneurons of the fly compound eye in situ with the use of intracellular recordings. Iontophoretical QX-314 injections, Lucifer yellow marking, and (discontinuous) current-clamp method together with transfer function analysis were used to characterize the neural signal processing mechanisms in these neurons. 2. A light-OFF spike was seen in one identified anatomic subtype (L3, n = 6) of the three first-order visual interneurons (L1, L2, and L3, or LMCs) when recorded from synaptic region (i.e., in the 1st visual ganglion, lamina ganglionaris) in dark-adapted conditions. Hyperpolarization of the membrane potential by current caused the identified L1 (n = 4), as well as L3 (n = 6), to produce an OFF spike, a number of action potentials, and some subthreshold depolarizations after the light-ON response. In L2 the OFF spike or action potentials could not be elicited. 3. To produce action potentials in L1 and L3, it was found to be necessary to hyperpolarize the cells approximately 35-45 mV (n = 43) below the resting potential (RP) in the synaptic zone. Recordings from the axons of these cells revealed that near the second neuropil (chiasma) the threshold of these spikes was near to (approximately 10 mV below, n = 16) or even at the RP when an ON spike was also produced (n = 4). 4. The recorded spikes were up to 54 mV in amplitude, appeared with a maximum frequency of up to 120 impulses/s, and had a duration of approximately 8 ms. In L1 and L3 the spikes were elicited either after a light pulse (L3) or after a negative current step that was superimposed on a hyperpolarizing steady-state current (L3 and L1). A positive current step (similarly superimposed on a hyperpolarizing steady-state current) also triggered the spikes during the step. 5. Iontophoretic injection of a potent intracellularly effective blocker of voltage-gated sodium channels, QX-314, irreversibly eradicated the spikes and subthreshold depolarizations (n = 5). In addition, further injections elongated the light-ON responses and decreased or even abolished the light-OFF response. 6. Negative prepulses followed by positive current steps were applied from the RP, to test the activation-inactivation properties of the channels responsible for the OFF spike.(ABSTRACT TRUNCATED AT 400 WORDS)
Functional changes in dorsal root ganglion cells after chronic nerve constriction in the rat
Authors: Xie Y. , Zhang J. , Petersen M. , LaMotte R. H.
Published: December 2017

1. We studied the effects of a chronic nerve constriction on the evoked responses in dorsal root fibers in the rat to norepinephrine and to thermal stimuli applied either to the dorsal root ganglion (DRG) or the site of nerve injury. We recorded a total of 59 C fibers, 15 A delta-fibers, and 46 A beta-fibers from the L5 dorsal root of the rats 11-52 days after a loose ligation of the ipsilateral sciatic nerve. Most fibers were identified by the presence of spontaneous activity (SA) that originated partially at and/or proximal to the injury site. In addition, we recorded 20 C fibers, 1 A delta-fiber, and 28 A beta-fibers from the dorsal roots of normal, uninjured neurons. 2. In nerve-injured rats, the SA of some C fibers was generally increased by cooling and decreased by heating either site. In contrast, the SA of most A beta-fibers was increased by heating either the injury site or the DRG. Cooling the DRG decreased SA in A beta-fibers, whereas cooling the injury site typically had no effect. Excitatory responses were not evoked in any fiber group when the same thermal stimuli were applied to the nerve or DRG tested in normal, uninjured rats. 3. Norepinephrine (< 0.5 mM) applied either to the injury site or the DRG increased the SA of most C fibers and A delta-fibers but only a minority of A beta-fibers in previously injured nerves. The threshold concentration for excitation of the DRG somata of C fibers was 0.01 mM. No effects were found for fibers in uninjured nerves. 4. The effect of norepinephrine was blocked by a pretreatment with yohimbine, an alpha 2-blocker, but not with prazosin, an alpha 1-blocker. 5. Stimulation of the sympathetic trunk (L2-L3) excited most C fibers and a minority of A beta-fibers. In contrast, the SA of a minority of C fibers and A beta-fibers was depressed during sympathetic stimulation. 6. After a chronic nerve constriction the DRG becomes a source of abnormal activity modulated by sympathetically released norepinephrine acting on alpha 2 receptors in DRG somata. This neuropathic activity may contribute to cutaneous pain and hyperalgesia.
Monaural inhibition in cat auditory cortex
Authors: Calford M. B. , Semple M. N.
Published: December 2017

1. Several studies of auditory cortex have examined the competitive inhibition that can occur when appropriate sounds are presented to each ear. However, most cortical neurons also show both excitation and inhibition in response to presentation of stimuli at one ear alone. The extent of such inhibition has not been described. Forward masking, in which a variable masking stimulus was followed by a fixed probe stimulus (within the excitatory response area), was used to examine the extent of monaural inhibition for neurons in primary auditory cortex of anesthetized cats (barbiturate or barbiturate-ketamine). Both the masking and probe stimuli were 50-ms tone pips presented to the contralateral ear. Most cortical neurons showed significant forward masking at delays beyond which masking effects in the auditory nerve are relatively small compared with those seen in cortical neurons. Analysis was primarily concerned with such components. Standard rate-level functions were also obtained and were examined for nonmonotonicity, an indication of level-dependent monaural inhibition. 2. Consistent with previous reports, a wide range of frequency tuning properties (excitatory response area shapes) was found in cortical neurons. This was matched by a wide range of forward-masking-derived inhibitory response areas. At the most basic level of analysis, these were classified according to the presence of lateral inhibition, i.e., where a probe tone at a neuron's characteristic frequency was masked by tones outside the limits of the excitatory response area. Lateral inhibition was a property of 38% of the sampled neurons. Such neurons represented 77% of those with nonmonotonic rate-level functions, indicating a strong correlation between the two indexes of monaural inhibition; however, the shapes of forward masking inhibitory response areas did not usually correspond with those required to account for the "tuning" of a neuron. In addition, it was found that level-dependent inhibition was not added to by forward masking inhibition. 3. Analysis of the discharges to individual stimulus pair presentations, under conditions of partial masking, revealed that discharges to the probe occurred independently of discharges to the preceding masker. This indicates that even when the masker is within a neuron's excitatory response area, forward masking is not a postdischarge habituation phenomenon. However, for most neurons the degree of masking summed over multiple stimulus presentations appears determined by the same stimulus parameters that determine the probability of response to the masker.(ABSTRACT TRUNCATED AT 400 WORDS)
Analysis of short-latency reflexes in human elbow flexor muscles
Authors: Stein R. B. , Hunter I. W. , Lafontaine S. R. , Jones L. A.
Published: December 2017

1. A motor and digital controller have been developed to apply rapid stretches to the human elbow joint. The digital controller returns the forearm to the initial position before the reflex contraction. Thus short-latency reflex responses can be cleanly separated in time from the mechanical effects of the stretch under a wide variety of loading conditions. 2. The reflex force varies linearly with the velocity of stretch over nearly 2 orders of magnitude. The reflex force also varies linearly with the tonic level of force over the entire range of forces studied (0-100 N). This contrasts sharply with, for example, the human ankle joint, which shows a very limited linear range. 3. As the digital controller is made more compliant (less stiff), reflex shortening increases dramatically and becomes more prolonged, whereas the reflex force becomes somewhat smaller and shorter. With compliant loads and the brief stretches we applied, the reflex shortening is approximately equal to the stretch that generated it. 4. Simulations of the results confirm that the dependence of reflex shortening and force on the stiffness of the load is mainly determined by the mechanics of the limb and muscles. The simulations also indicate that 1) the gain of the reflex is as high as it can be without causing instability and 2) the presence of a rectification nonlinearity (e.g., lengthening the muscle produces a reflex, but shortening the muscle does not) is mainly responsible for preserving the stability of the elbow system.