bluuebunny/crossref_metadata_2025 huggingface dataset:
Organization of inhibition in the rat olfactory bulb external plexiform layer
Authors: Ezeh P. I. , Wellis D. P. , Scott J. W.
Published: December 2017

1. Intracellular recordings were made from the output neurons (mitral and tufted cells) of the rat olfactory bulb during electrical orthodromic stimulation of the olfactory nerve layer (ONL) and antidromic stimulation of the lateral olfactory tract and posterior piriform cortex (pPC) to test for physiological differences among the neuron types. Many of these neurons were identified by intracellular injections of biocytin, and others were identified by their pattern of antidromic activation. 2. Both marked and unmarked mitral cells showed large inhibitory postsynaptic potentials (IPSPs) in response to antidromic stimulation of the pPC, whereas tufted cells exhibited small IPSPs in response to pPC stimulation. Tufted cells, however, showed large IPSPs in response to ONL stimulation. In many cases, these tufted cell responses to ONL stimulation were larger than the mitral cell responses. The marked superficial tufted cells, those with basal dendrites in the superficial sublayer of the external plexiform layer (EPL), had the smallest IPSPs in response to pPC stimulation. These data support anatomic observations suggesting that the granule cell populations responsible for the IPSPs may be different for mitral and for superficial tufted cells. 3. The different types of output cells also showed differences in their responses to orthodromic stimulation. Type I mitral cells, which have basal dendrites confined to the deep sublayer of the EPL, were significantly less excitable by ONL stimulation than were the type II mitral cells, which have basal dendrites distributed within the intermediate sublayer of the EPL. Half of the type I mitral cells could not be excited at all by ONL stimulation. Superficial tufted cells showed even greater orthodromic excitability than type II mitral cells, usually responding to ONL stimulation with two or more spikes. 4. The ionic basis of the IPSPs in the superficial tufted cells appeared similar to those described for mitral cells. These IPSPs could be reversed by chloride injection and were associated with increased membrane conductance. 5. For both mitral and tufted cells, the number of ONL electrodes evoking IPSPs was greater than the number evoking spikes. These data suggest a kind of center-surround organization of inputs to these cells from the ONL, although this does not yet imply that the sensory receptive field of these output cells has a center-surround organization. 6. In conclusion, the properties of rat olfactory bulb output cells correlate with the sublayers of the EPL in which their basal dendrites lie.(ABSTRACT TRUNCATED AT 400 WORDS)
Low- and high-frequency membrane potential oscillations during theta activity in CA1 and CA3 pyramidal neurons of the rat hippocampus under ketamine-xylazine anesthesia
Authors: Soltesz I. , Deschenes M.
Published: December 2017

1. Intracellularly recorded low- and high-frequency (4-6 and 25-50 Hz, respectively), rhythmic, spontaneous membrane potential oscillations were investigated in pyramidal neurons of the rat hippocampus in vivo, during theta (theta, 4-6 Hz) electroencephalographic (EEG) activity, under ketamine-xylazine anesthesia. 2. The EEG activity showed two spectral peaks, one in the theta range, the other at higher frequencies (25-50 Hz). On the basis of their electrophysiological and pharmacological properties, it was concluded that the EEG theta-waves, and the fast EEG rhythm, recorded during ketamine-xylazine anesthesia, share the basic properties of those theta and fast rhythms that are recorded under the effects of other types of anesthetics. 3. When intracellular recordings (n = 32) were made with electrodes filled with potassium-acetate (K-acetate), the only CA1 and CA3 pyramidal cells (PCs) considered for further analysis were those that did not fire rhythmically at most or each cycle of the theta rhythm at the resting membrane potential. During EEG-theta, the membrane potential (Vm) of these cells showed a prominent oscillation (3-15 mV) with frequencies similar to those of the EEG-theta (the intracellular theta rhythm, intra-theta). 4. The frequency of the intra-theta was independent of the Vm. However, the phase difference between the intra-theta and the EEG-theta was voltage dependent in both types of cells. CA1 PCs showed a large (120-180 degrees, where 360 degrees is the full cycle), gradual shift in the phase difference between the intra-theta and the EEG-theta, when the membrane was hyperpolarized to -85 from -65 mV. Although CA3 PCs displayed a larger variability in their phase-voltage relations, a voltage-dependent phase shift (90-180 degrees) could be observed in CA3 PCs as well. 5. Although the amplitude of the intra-theta in both CA1 and CA3 PCs could display large, sudden, spontaneous changes at a given Vm, the amplitude-Vm plots tended to show a minimum between -70 and -80 mV. Spontaneous changes in the amplitude of the intra-theta did not affect the phase difference between the intra- and the EEG-theta rhythms. 6. Intracellular injection of QX-314 (50-100 mM) did not change the phase-Vm or the amplitude-Vm relationships of CA1 PCs. 7. Intracellular injection of chloride (Cl-) ions greatly reduced the voltage dependency of the phase difference and revealed fast (duration: 20-25 ms), depolarizing potentials (5-20 mV), which appeared at high frequencies (25-50 Hz), amplitude modulated at theta-frequencies.(ABSTRACT TRUNCATED AT 400 WORDS)
Spatial patterns of increased spinal cord membrane-bound protein kinase C and their relation to increases in 14C-2-deoxyglucose metabolic activity in rats with painful peripheral mononeuropathy
Authors: Mao J. , Mayer D. J. , Hayes R. L. , Price D. D.
Published: December 2017

1. Three-dimensional spatial patterns of changes in membrane-bound protein kinase C (PKC) were examined in the lumbar spinal cords (L1-L5) of rats with an experimental painful peripheral mononeuropathy. Painful peripheral mononeuropathy was produced by loosely ligating the rat's common sciatic nerve, resulting in chronic constrictive nerve injury (CCI). Changes in spinal cord membrane-bound PKC distribution were assayed by employing an established quantitative [3H]-phorbol-12,13-dibutyrate ([3H]PDBu) autoradiographic assay, which includes spinal cord sectioning, incubation of spinal cord sections with [3H]PDBu, production of autoradiographs, and computer-assisted image processing. 2. Sciatic nerve ligation induced demonstrable thermal hyperalgesia in response to radiant heat stimulation and spontaneous pain-related behaviors (such as lifting of the nerve-ligated hind paw) in CCI rats 3, 7, and 10 days after unilateral sciatic nerve ligation. 3. Consistent with behavioral changes, CCI rats examined 3 or 10 days after sciatic nerve ligation displayed a three-dimensional pattern of increased membrane-bound PKC in the lumbar spinal cord (L1-L5) strikingly different from that of sham-operated rats: in the dorsoventral dimension, reliable increases in membrane-bound PKC occurred mainly within spinal cord laminae I-IV and V-VI in CCI rats; in the ipsilateral-contralateral dimension, changes in membrane-bound PKC were seen on both sides of the spinal cord in CCI rats with reliably higher levels of membrane-bound PKC on the side ipsilateral than on the side contralateral to sciatic nerve ligation; in the rostrocaudal dimension, increases in membrane-bound PKC in the spinal cord dorsal horns of CCI rats extended from spinal segments L2-L5. 4. Both three-dimensional increases in spinal cord membrane-bound PKC and nociceptive behaviors (thermal hyperalgesia and spontaneous pain behaviors) in CCI rats were reliably reduced after three daily intrathecal treatments with 80 nmol GM1 ganglioside (a glycosphingolipid shown to prevent PKC translocation/activation), the first of which was given 1 h after sciatic nerve ligation. This reduction was seen 24 h but not 7 days after the last GM1 ganglioside treatment. 5. This three-dimensional increase in membrane-bound PKC in the spinal cord dorsal horn of CCI rats displayed high correlations with thermal hyperalgesia and with spontaneous pain-related behaviors in CCI rats observed both 3 and 10 days after sciatic nerve ligation. Similar correlations were observed between decreases in levels of membrane-bound PKC in the spinal cord dorsal horn and the attenuation of nociceptive behaviors in CCI rats after three daily intrathecal treatments with GM1 ganglioside.(ABSTRACT TRUNCATED AT 400 WORDS)
Inward rectification and its effects on the repetitive firing properties of bulbospinal neurons located in the ventral part of the nucleus tractus solitarius
Authors: Dekin M. S.
Published: December 2017

1. An in vitro brain stem slice from adult guinea pigs was used to study the effects of membrane hyperpolarization in two classes of bulbospinal neurons, called types I and II, from the ventral parts of the nucleus tractus solitarius (vNTS). These bulbospinal neurons project to the phrenic motor nucleus and make up the dorsal respiratory group, a sensorimotor integrating area for rhythmic breathing movements. 2. Negative current injections (1 s long) were used in the discontinuous current-clamp mode to study the input resistance (Rin) in both classes of bulbospinal vNTS neurons. The mean Rin for type I neurons was 88.7 +/- 13.8 (SD) M omega (n = 19) and for type II neurons was 92.6 +/- 14.0 M omega (n = 16). Both classes of neurons displayed a depolarizing sag and inward rectification during negative current injections to membrane-potential levels less than or equal to -70 mV. The magnitude of the depolarizing sag became larger as the size of the negative current step was increased. On release from hyperpolarization, both cell types also exhibited a large anode break hyperpolarization (ABH). 3. The ABH was abolished in the presence of 5 mM 4-amino-pyridine (4-AP), whereas the depolarizing sag and inward rectification were not affected. In the place of the ABH, a small postinhibitory rebound (PIR) depolarization was observed on release from hyperpolarization. The magnitude of PIR was dependent on the size of the depolarizing sag. In the presence of both 5 mM 4-AP and 5 mM Cs+, the depolarizing sag and PIR were completely blocked, whereas Rin was increased. 4. The ionic currents underlying the ABH and depolarizing sag were directly observed by the use of the discontinuous single-electrode voltage-clamp technique. The ABH was caused by activation of an A-current (IKA). The depolarizing sag was associated with a hyperpolarization-activated inward current (IH), which was activated at membrane-potential levels less than or equal to -70 mV. The peak amplitude of IH in type I neurons was -335 +/- 16 pA (n = 13) and in type II cells was -327 +/- 14 pA (n = 11). 5. IH currents did not display inactivation during the hyperpolarizing voltage step. The IH current became larger when [K+]o was increased from 4 mM (control) to 12 mM and was blocked in the presence of 5 mM Cs+. The estimated reversal potential for the IH current was -41.5 +/- 4.8 mV (n = 8).(ABSTRACT TRUNCATED AT 400 WORDS)
Sensitivity of auditory nerve fibers to spectral notches
Authors: Poon P. W. , Brugge J. F.
Published: December 2017

1. Listeners use direction-dependent spectral cues introduced by the torso, head, and pinnae to localize the source of a sound in space. Among the prominent direction-dependent spectral features in the free field-to-eardrum transfer function are narrow regions of low acoustic energy referred to as spectral notches. In this paper, we studied the sensitivity of single auditory nerve fibers in the barbiturate-anesthetized cat to broadband noise that had been filtered by a function whose shape approximated natural notches in the free field-to-eardrum transfer function. 2. Two experimental paradigms were employed. The first was the repeated presentation of a burst of broadband noise filtered by the simulated-notch function. Center frequency of the notch was held constant at or around the fiber characteristic frequency (CF). We refer to this as a "stationary" notch stimulus. The second paradigm was the repeated presentation of a broadband noise that was constructed from noise segments, each filtered by the simulated notch, whose CF was incremented and then decremented in a systematic way. We refer to this as a "moving" notch stimulus. Results from these two paradigms were compared with respect to notch detection. 3. Data were obtained from 161 single auditory nerve fibers having CFs ranging from 0.4 to 40 kHz. Most fibers studied had CFs > 5 kHz, and they detected the presence of the spectral notch in an intensity- and frequency-dependent manner. Each fiber responded vigorously to the presence of broadband noise. When the CF of the notch encroached on the response area of the fiber, there was a demonstrable reduction in discharge rate. The greatest reduction in discharge rate occurred when the notch was centered at the fiber's CF and when the level of the notch signal was some 15-55 dB above the fiber's noise threshold. There was close association in the frequency-intensity plane between the position of the most effective notch and the fiber's threshold tuning curve. 4. For high-spontaneous rate fibers, a moving-notch stimulus, but not a stationary one, reduced the discharge below the spontaneous rate at and in the immediate vicinity of the most effective notch frequency. This increases sensitivity to a spectral notch and suggests a mechanism by which localization ability is enhanced when there is relative motion between a sound source and the head.(ABSTRACT TRUNCATED AT 400 WORDS)
Characteristics of spontaneous and evoked EPSPs recorded from dentate spiny hilar cells in rat hippocampal slices
Authors: Scharfman H. E.
Published: December 2017

1. Excitation of the spiny subtype of hilar neurons in the fascia dentata was characterized by intracellular recording from hilar cells in hippocampal slices. Stimulation of the outer molecular layer was used to activate the perforant path. Evoked responses were examined, as well as the large spontaneous excitatory potentials that are a distinctive characteristic of spiny hilar cells. 2. Excitatory potentials that occurred spontaneously, as well as those that occurred in response to outer molecular layer stimulation, were similar among the cells that were sampled, regardless of morphological variations such as the presence or absence of thorny excrescences. Spontaneous and evoked excitatory postsynaptic potentials (EPSPs) were complex depolarizations that often had several discrete peaks. Spontaneous EPSPs increased in amplitude slightly with hyperpolarization, and evoked EPSPs clearly increased with hyperpolarization. 3. Applications of selective antagonists of excitatory amino acid receptors were used to determine which excitatory amino acid receptor mediates EPSPs of these cells. 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX) was used to block the receptor subtype selective for the agonists alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) and kainic acid (the "AMPA/kainate" receptor). 2-amino-5-phosphonovaleric acid (APV) was used to block receptors specific for the agonist N-methyl-D-aspartate (NMDA; the "NMDA" receptor). Perfusion with CNQX (5-25 microM) completely blocked all spontaneous and evoked excitation, even when activity was examined at relatively depolarized membrane potentials and a low concentration of extracellular magnesium (0.5 mM) was used. Under these conditions, APV (25-50 microM) had no detectable effect on spontaneous activity but did increase the stimulus strength required to elicit responses to outer molecular layer stimulation. 4. When extracellular magnesium was lowered to 0 mM (nominally), there was strong evidence for a contribution of NMDA receptors to spontaneous and evoked EPSPs. Thus, when cells were perfused with 0 mM extracellular magnesium and 5 microM CNQX, spontaneous depolarizations were present and EPSPs could be triggered by stimulation of the outer molecular layer. Both the spontaneous and evoked EPSPs were blocked by 25 microM APV. 5. Because gamma-aminobutyric acid (GABA)A receptors can cause depolarizations in hippocampal neurons, the GABAA receptor antagonist bicuculline was used to determine whether some of the EPSPs were mediated by GABAergic neurons that are normally activated by spontaneous release of excitatory amino acids. Bicuculline (5-25 microM) had no effect on spontaneous depolarizations, and led to an enhancement of evoked depolarizations. Therefore it does not appear that GABAA receptor-mediated depolarizations contribute to hilar cell depolarizations.(ABSTRACT TRUNCATED AT 400 WORDS)
Responsiveness to D-glucose in neurosecretory cells of crustaceans
Authors: Garcia E. , Benitez A. , Onetti C. G.
Published: December 2017

1. An electrophysiological study of the D-glucose sensitivity of X-organ (XO) neurosecretory cell bodies in crayfish was carried out with the use of microelectrodes, perforated, and cell-attached patch-clamp techniques. 2. Glucose depolarizes the membrane potential of XO cells in a concentration-dependent manner. 3. Depolarization produced by glucose initiates a change in the pattern of electrical activity. Silent cells began to discharge action potentials. When bursting cells are depolarized by glucose, their action potentials are no longer grouped in bursts or disappear entirely. 4. Although the membrane potential returns to its initial value after removing glucose from the bath, discharge patterns of the cells may remain different. This suggests that besides the depolarizing effect, once the cells have been exposed to glucose, the sugar switches on a process that is maintained for a long time. 5. Glucose produced a reduction of membrane steady-state conductance, and a shift of reversal potential of membrane currents to a more positive value. 6. Depolarization induced by D-glucose appears to be related with a closure of potassium channels. 7. Glucose effect was thought to be generated by a product of metabolism that would act as intracellular mediator.
Synaptic integration in an excitable dendritic tree
Authors: Mel B. W.
Published: December 2017

1. Compartmental modeling experiments were carried out in an anatomically characterized neocortical pyramidal cell to study the integrative behavior of a complex dendritic tree containing active membrane mechanisms. Building on a previously presented hypothesis, this work provides further support for a novel principle of dendritic information processing that could underlie a capacity for nonlinear pattern discrimination and/or sensory processing within the dendritic trees of individual nerve cells. 2. It was previously demonstrated that when excitatory synaptic input to a pyramidal cell is dominated by voltage-dependent N-methyl-D-aspartate (NMDA)-type channels, the cell responds more strongly when synaptic drive is concentrated within several dendritic regions than when it is delivered diffusely across the dendritic arbor. This effect, called dendritic "cluster sensitivity," persisted under wide-ranging parameter variations and directly implicated the spatial ordering of afferent synaptic connections onto the dendritic tree as an important determinant of neuronal response selectivity. 3. In this work, the sensitivity of neocortical dendrites to spatially clustered synaptic drive has been further studied with fast sodium and slow calcium spiking mechanisms present in the dendritic membrane. Several spatial distributions of the dendritic spiking mechanisms were tested with and without NMDA synapses. Results of numerous simulations reveal that dendritic cluster sensitivity is a highly robust phenomenon in dendrites containing a sufficiency of excitatory membrane mechanisms and is only weakly dependent on their detailed spatial distribution, peak conductances, or kinetics. Factors that either work against or make irrelevant the dendritic cluster sensitivity effect include 1) very high-resistance spine necks, 2) very large synaptic conductances, 3) very high baseline levels of synaptic activity, and 4) large fluctuations in level of synaptic activity on short time scales. 4. The functional significance of dendritic cluster sensitivity has been previously discussed in the context of associative learning and memory. Here it is demonstrated that the dendritic tree of a cluster-sensitive neuron implements an approximative spatial correlation, or sum of products operation, such as that which could underlie nonlinear disparity tuning in binocular visual neurons.
Response properties of neurons in temporal cortical visual areas of infant monkeys
Authors: Rodman H. R. , Scalaidhe S. P. , Gross C. G.
Published: December 2017

1. Inferior temporal cortex (IT) is a "high-order" region of primate temporal visual cortex implicated in visual pattern perception and recognition. To gain some insight into the development of this area, we compared the properties of single neurons in IT in infant monkeys ranging from 5 wk to 7 mo of age with those of neurons in IT in adult animals. Both anesthetized and awake behaving paradigms were used. 2. In immobilized infant monkeys under nitrous oxide anesthesia, the incidence of visually responsive cells was markedly less than in adult monkeys studied under similar conditions. In infants 4-7 mo of age, only half of IT neurons studied were visually responsive, compared with > 80% in adult monkeys. In monkeys < 4 mo old, even fewer (< 10%) could be visually driven. "Habituation" of IT cells to repeated stimulus presentation appeared more pronounced in infant monkeys under nitrous oxide anesthesia than in adult animals. 3. IT cells in the anesthetized infant monkeys that did respond showed receptive field properties similar to those of responsive adult IT neurons studied under similar conditions. Two thirds of the receptive fields plotted in the anesthetized 4 to 7-mo-old group were bilateral, and median field size did not differ between the infants and comparable adult groups, being approximately 20 degrees on a side in each case. 4. In contrast to the results obtained under anesthesia, most IT cells in alert infant monkeys 5 wk-7 mo of age (80%) were responsive to visual stimuli, and this incidence of visually responsive IT neurons did not differ from that obtained in awake adult macaques. However, response magnitude, measured as spikes per second above baseline rate, was significantly lower in the infant alert sample than in the adult control (5.2 vs. 12.6 spikes/s, mean +/- SE, deviation from spontaneous rate, respectively). 5. In addition to having lower magnitudes of visual response, IT cells in the awake infants also tended to have longer and more variable latencies. The overall mean for the infant cells was 196 ms, compared with an overall mean of 140 ms for IT neurons in the alert control adult. 6. Although the magnitude of response of neurons in alert infant IT cortex was lower overall, the incidence and features of stimulus selectivity shown by alert infant IT neurons were strikingly similar to those of IT cells of both anesthetized and unanesthetized adult monkeys.(ABSTRACT TRUNCATED AT 400 WORDS)
Response characteristics of lamb pontine neurons to stimulation of the oral cavity and epiglottis with different sensory modalities
Authors: Sweazey R. D. , Bradley R. M.
Published: December 2017

1. To better understand sensory information processing in pontine neurons that receive afferent fiber terminations from oral cavity and upper airway receptors, we investigated the response characteristics of single neurons to stimulation of the oral cavity and epiglottis with different stimulus modalities. These response characteristics were then compared with previously recorded response properties of neurons located in other brain stem regions that receive oral cavity and upper airway sensory inputs. 2. Receptive field sizes of pontine neurons were mapped, and responses to mechanical, thermal, and chemical stimuli were determined. A total of 47 neurons were isolated and most neurons were located near the dorsomedial border of the rostral trigeminal subnucleus oralis and caudal principal trigeminal nucleus. The likelihood that a particular stimulus modality would elicit a response was somewhat dependent on a neuron's location. Neurons that responded to chemical stimuli were always located outside the trigeminal nucleus, whereas neurons that responded exclusively to mechanical or thermal stimuli were more frequently located in the trigeminal nucleus. Receptive fields were mapped for 45 of the 47 neurons. Forty-three of the neurons had a single ipsilateral receptive field and > 80% of the receptive fields were > 100 mm2. The majority of neurons responded to only one of the three stimulus modalities. The remaining neurons were multimodal and the combination of stimulus modalities most frequently observed was mechanical and chemical. 3. Mechanical stimuli were the most effective of the three stimulus modalities, eliciting responses in > 65% of the neurons. Neurons that responded to mechanical stimuli were generally rapidly adapting and a moving stimulus was more effective than a punctate stimulus. Mechanosensitive neurons that also responded to chemical stimuli exhibited larger mean response frequencies than mechanosensitive neurons that did not respond to chemical stimuli. Chemical stimuli elicited responses in about half the neurons. A greater percentage of neurons with receptive fields on the epiglottis than neurons with oral cavity receptive fields responded to chemical stimuli. The effectiveness of a chemical stimulus was dependent on a neuron's receptive field. NH4Cl was the most effective stimulus for neurons with receptive fields located in the oral cavity, whereas KCl was more effective for neurons with receptive fields on the epiglottis. Thermal stimuli were relatively ineffective whatever the location of a neuron's receptive field. The majority of neurons showed an increase in response frequency to cooling the receptive field and in all thermosensitive neurons the response was restricted to the dynamic phase of thermal stimulation.(ABSTRACT TRUNCATED AT 400 WORDS)
Synaptic noise and multiquantal release at dendritic synapses
Authors: Korn H. , Bausela F. , Charpier S. , Faber D. S.
Published: December 2017

1. The quantal nature of inhibitory synaptic noise recorded intracellularly from the lateral dendrite of the goldfish Mauthner cell was studied, using new detection and measurement procedures that eliminate operator intervention. In addition, we employed an analytical algorithm, not previously applied to this problem, which treats composite amplitude distributions as mixtures of gaussians of unknown separations and variances. 2. As in the soma of this neuron, the dendritic inhibitory noise is quantal, with the exception that in the dendrite multiple equally spaced classes may persist in the presence of tetrodotoxin (TTX), an observation that may be correlated with the finding that the inhibitory afferents at this level often contain more than one release site. The validity of the analysis was confirmed by superfusing with saline containing low calcium and high magnesium, which reduces composite histograms that are gaussian mixtures to a single class, equal in amplitude to that of the first component detected in the control. 3. These results suggest that spontaneous exocytotic events may be synchronized at adjacent active zones within single terminals and that lowering the probability of release by reducing calcium may then be a more effective method for isolating single miniature events than is TTX.
Nitric oxide inhibitors facilitate the induction of hippocampal long-term potentiation by modulating NMDA responses
Authors: Kato K. , Zorumski C. F.
Published: December 2017

1. The effects of the competitive nitric oxide (NO) synthase inhibitor, L-nitroarginine (L-NOArg), on synaptically activated N-methyl-D-aspartate (NMDA) currents and the induction of long-term potentiation (LTP) were studied in the CA1 region of rat hippocampal slices. 2. Application of 10 microM L-NOArg increased the amplitude of NMDA currents by approximately 50% in the presence of 2 mM extracellular Mg2+. This augmentation occurred within minutes of L-NOArg administration and was readily reversible on removal of the drug. L-arginine (100 microM) overcame the enhancement produced by L-NOArg. 3. At 5-100 microM, 10-25-min applications of L-NOArg facilitated the induction of LTP produced by a single 100 Hz X 300 ms tetanus. In control slices, the 100 Hz X 300 ms tetanus was insufficient to induce LTP. The development of LTP in L-NOArg-treated slices was inhibited by 50 microM D-2-amino-5-phosphonovalerate (D-APV), and the effects of L-NOArg were overcome by 10-fold higher concentrations of L-arginine but not by D-arginine. 4. Hemoglobin, an agent that binds NO extracellularly, also facilitated NMDA currents and the development of LTP when administered at 10 microM. 5. These results suggest that tonically released NO modulates the threshold for LTP in the CA1 hippocampal region and are consistent with prior studies indicating that untimely activation of NMDA receptors and release of NO inhibit LTP.
Taste responses of neurons in the nucleus of the solitary tract of awake rats: an extended stimulus array
Authors: Nakamura K. , Norgren R.
Published: December 2017

1. Fifty-seven taste neurons were isolated in the nucleus solitary tract (NST) and tested with 15 sapid chemicals. On average, NST neurons responded well to NaCl, sucrose, monosodium L-glutamate (MSG), NaNO3, and glycine (mean = 8.2-11.0 spikes/s). Mean responses to KCl, NH4Cl, HCl, malic acid, and quinine HCl (QHCl) were low (mean = 0.7-2.9). The average responses to the other stimuli (citric acid, MgCl2, fructose, maltose, and polycose) fell between these extremes (mean = 4.3-5.1). 2. On the basis of the largest response to the four standard stimuli, the neurons were classified as follows: 15 NaCl-best, 23 sucrose-best, 17 citric acid-best, and 2 QHCl-best. 3. The NaCl-best neurons responded robustly and nearly equally to the three sodium salts (mean = 15.7-20.8) but much less so and more variably to the nonsodium, chloride salts (mean = -0.1-4.6). Sucrose-best neurons responded strongly to sucrose, glycine, and MSG (mean = 13.7-17.8), but only moderately to the other sugars (fructose and maltose) and to polycose (mean = 8.4, 9.8, and 8.8, respectively). 4. Citric acid-best neurons responded moderately to citric and malic acid (mean = 9.4 and 4.7), but less so to HCl (mean = 3.1). The two QHCl-best neurons responded moderately to QHCl and MgCl2 (mean = 12.0 and 9.5), but weakly or not at all to the other stimuli (mean = -1.1-3.1). 5. Unlike parabrachial taste neurons, none of the medullary taste cells responded specifically to Cl(-)-containing chemicals. The responses that did occur to nonsodium salts were weak and variable and often occurred in either citric acid-best or QHCl-best neurons, rather than in those that responded vigorously to sodium salts. Similar relationships have been observed in anesthetized preparations. 6. A hierarchical cluster analysis for 57 neurons across 15 stimuli produced four second-order clusters that consisted primarily of NaCl-best, sucrose-best, citric acid-best, and QHCl-best neurons, respectively. Although the analysis for neurons produced only four such clusters, a similar analysis for the 15 stimuli separated the sodium salts (NaCl and NaNO3), nonsodium salts (KCL, NH4Cl, and MGCl2, sweeteners (sucrose, maltose, fructose, and glycine), acids (citric acid and malic acid), and QHCl. 7. Monosodium glutamate activated both NaCl-best and sucrose-best neurons, but the stimulus analysis clumped it with the sodium salts.(ABSTRACT TRUNCATED AT 400 WORDS)
Axon terminal hyperexcitability associated with epileptogenesis in vitro. II. Pharmacological regulation by NMDA and GABAA receptors
Authors: Stasheff S. F. , Mott D. D. , Wilson W. A.
Published: December 2017

1. The preceding report presented evidence that the kindling-like induction of electrographic seizures (EGSs) in the hippocampal slice is accompanied by a lasting increase in the excitability of CA3 axon terminals, which is manifested by an increase in action-potential initiation at this site. In this report we explore the role of the N-methyl-D-aspartate (NMDA) receptor in the induction and maintenance of this antidromic firing, as well as the role of the gamma-aminobutyric acid type A (GABAA) receptor in regulating this activity once it has been induced. 2. Kindling-like stimulus trains (60 Hz, 2 s) were delivered to s. radiatum of CA3 at 10-min intervals. As EGSs developed in control artificial cerebrospinal fluid (ACSF), the frequency of axon terminal firing increased markedly (by 10.33 +/- 3.29 spikes/min, mean +/- SE P << 0.01). The prior application of the competitive NMDA antagonist D-2-amino-5-phosphonovaleric acid (D-APV, 50 or 100 microM) prevented the induction of EGSs and suppressed the increase in terminal firing seen in control ACSF (mean increase 1.06 +/- 1.11 spikes/min, P < 0.02). However, when D-APV was applied only after EGSs and antidromic spikes were induced in control ACSF, it failed to alter the frequency of terminal firing (mean 6.44 +/- 2.03 in control ACSF, 8.89 +/- 2.31 in APV; P >> 0.1). Thus the NMDA receptor is required for the induction but not maintenance of increased axon terminal firing, as we previously have shown to be the case for EGSs.(ABSTRACT TRUNCATED AT 250 WORDS)
Late expiratory inhibition of stage 2 expiratory neurons in the cat--a correlate of expiratory termination
Authors: Klages S. , Bellingham M. C. , Richter D. W.
Published: December 2017

1. Intracellular recordings were made from stage 2 expiratory bulbospinal neurons (E2Ns) in the caudal part of the ventral respiratory group in pentobarbitone-anesthetized cats, to characterize changes in neuronal input resistance (Rn) and synaptic inhibition occurring at the time of the expiratory-inspiratory phase transition of the respiratory cycle. 2. Rn was maximal between 30-90% of stage 2 expiration, but decreased significantly during the last 10% of stage 2 expiration. Mean normalized Rn for 60-90% of stage 2 expiration was 0.9 +/- 0.02, while mean Rn during the last 10% of stage 2 expiration was 0.68 +/- 0.09 (n = 8). This decrease in Rn began 200-300 ms before rapid hyperpolarization of E2N membrane potential and onset of phrenic nerve activity. 3. Under conditions of strong central respiratory drive, constant injection of positive current into E2Ns sometimes revealed a transient membrane hyperpolarization that straddled the expiratory-inspiratory phase transition. During this transient event, Rn was markedly reduced. 4. Intracellular injection of Cl- or NO3- ions into E2Ns produced reversal of chloride-dependent inhibitory synaptic potentials (IPSPs). Comparison of averages of membrane potential pattern over the whole respiratory cycle during control conditions and IPSP reversal revealed several periods of synaptic inhibition: 1) weak but progressively increasing synaptic inhibition during the second half of stage 2 expiration, 2) strong transient synaptic inhibition beginning 200-300 ms before the onset of phrenic nerve activity and ending shortly after the onset of phrenic nerve activity, and 3) strong but progressively decreasing synaptic inhibition throughout inspiration.(ABSTRACT TRUNCATED AT 250 WORDS)
Effects of volatile anesthetics on the kinetics of inhibitory postsynaptic currents in cultured rat hippocampal neurons
Authors: Jones M. V. , Harrison N. L.
Published: December 2017

1. The effects of the volatile anesthetics enflurane, halothane, and isoflurane on gamma-aminobutyric acid (GABA) receptor-mediated inhibitory postsynaptic currents (IPSCs) were studied in cultured rat hippocampal neurons. The experimental concentrations of anesthetics were measured directly using gas chromatography. All three anesthetics increased the overall duration of IPSCs, measured as the time to half-decay (T1/2). Clinically effective concentrations of anesthetics [between 0.5 and 1.5 times MAC (minimum alveolar concentration)] produced between 100 and 400% increases in T1/2. These effects were fully reversible, and did not involve alterations in the reversal potential for the IPSC (EIPSC). 2. The decay of the IPSC was fitted as a sum of two exponential functions, yielding a fast component (tau fast = 20 ms), and a slow component (tau slow = 77 ms), such that the fast component accounted for 79% of the IPSC amplitude and 52% of the total charge transfer. All three anesthetics produced concentration-related increases in the amplitude and charge transfer of the slow component, while simultaneously decreasing the amplitude and charge transfer of the fast component. Thus T1/2 approximated tau fast under control conditions, but approximated tau slow in the presence of the anesthetics. 3. Varying the calcium chelating agents in the recording pipettes had no effect on the quality or magnitude of alterations in IPSC kinetics produced by halothane, suggesting that variations in intracellular calcium levels are not required for the effect of halothane on the time course of the IPSC. 4. The (+)-stereoisomer of isoflurane produced greater increases in the duration of the IPSC than the (-)-isomer when applied at approximately equal concentrations, suggesting that there is a structurally selective site of interaction for isoflurane that modulates the GABAA receptor. 5. These results suggest that the previously shown abilities of volatile anesthetics to potentiate responses to exogenously applied GABA and to prolong the duration of GABA-mediated synaptic inhibition may be due to an alteration in the gating kinetics of the GABAA receptor/channel complex. Prolongation of synaptic inhibition in the CNS is consistent with the physiological effects that accompany anesthesia and may contribute to the mechanism of anesthetic action.
Hyperpolarization-activated cation current (Ih) in neurons of the medial nucleus of the trapezoid body: voltage-clamp analysis and enhancement by norepinephrine and cAMP suggest a modulatory mechanism in the auditory brain stem
Authors: Banks M. I. , Pearce R. A. , Smith P. H.
Published: December 2017

1. Principal cells in the medial nucleus of the trapezoid body (MNTB) are part of a circuit in the superior olivary complex (SOC) that processes binaural information important for sound localization. MNTB cells have two voltage-dependent currents active near rest that contribute to these cells' highly nonlinear membrane properties and shape their responses to synaptic input. One of these currents, a low-threshold, 4-aminopyridine (4-AP)-sensitive K+ current, has been studied previously under current clamp. Using the single-electrode voltage-clamp technique, we have investigated the other of these currents, a hyperpolarization-activated, mixed cation current (Ih), in brain slices of the rat SOC. 2. Ih is responsible for a prominent "sag" in the voltage response to a steady hyperpolarizing current recorded under current clamp in MNTB cells. In voltage-clamp recordings, hyperpolarizing voltage steps from the resting potential elicited a large inward current that activated and deactivated with biexponential kinetics. Activation time constants were voltage dependent, with tau 1 and tau 2 = 246 and 1620 ms at -75 mV and 107 and 560 ms at -100 mV. 3. Ih was blocked by 1-5 mM cesium and had a reversal potential of -43 mV. Steady-state activation curves derived from tail currents yielded a half-activation voltage of -75.7 mV and slope factor of 5.7 mV, corresponding to < 10% activation of Ih at rest. 4. Application of norepinephrine (15-20 microM) or 8-bromoadenosine 3',5'-cyclic monophosphate (8-Br-cAMP) (1 mM) caused a depolarizing shift in the steady-state activation curve and decreased the activation time constants. The shift in the activation curve resulted in a large increase in the activation of Ih at rest, an inward shift in the holding current, and an increase in the resting membrane conductance. In current-clamp recordings, this increase in the resting activation level of Ih resulted in membrane depolarization of 2-3 mV in the absence of 4-AP, and 5-10 mV in the presence of 4-AP, an increase in the input conductance, and a reduction in the voltage sag in response to hyperpolarizing currents. 5. The resulting change in the resting point of MNTB cells exposed to norepinephrine or 8-Br-cAMP is likely to alter the responses of these cells to synaptic input, both via the direct effect on the resting membrane conductance and by changing the activation of the low-threshold, 4-AP-sensitive potassium current.(ABSTRACT TRUNCATED AT 400 WORDS)
Electrical properties of Y-79 cells, a multipotent line of human retinoblastoma
Authors: del Pilar Gomez M. , Waloga G. , Nasi E.
Published: December 2017

1. Whole-cell and perforated-patch tight-seal recording techniques were used to characterize the voltage-dependent membrane conductances of the Y-79 cells, a human retinoblastoma line composed of pluripotential retinal precursor cells. 2. Membrane resistance and capacitance were measured under current clamp, yielding approximate average values of 1.8 G omega and 26 pF, respectively. The cells are electrically excitable, and depolarization above -20 mV triggers slow action potentials. 3. Step depolarization of the membrane under voltage clamp elicits a high-threshold transient inward current, followed by a sustained, larger outward current. The outward current is carried by potassium ions, as determined by its susceptibility to blockage by K-channel antagonists [tetraethylammonium (TEA), Cs, and 4-aminopyridine (4-AP)] and insensitivity to reduction of external chloride concentration. 4. The isolated inward current displayed some unusual properties: its amplitude is directly related to extracellular calcium concentration, and replacement of calcium by magnesium completely abolishes it. However, none of the calcium channel antagonists tested (cadmium, nickel, nifedipine, and amiloride) exerted a substantial blockage. In addition, removal of external sodium or superfusion with tetrodotoxin significantly reduce the size of this current. 5. A single voltage-dependent conductance appears to underlie the inward current, because a variety of manipulations, such as changes in the holding potential, in the extracellular concentration of calcium or sodium, or superfusion with tetrodotoxin, failed to reveal the presence of kinetically distinct components. 6. The results suggest that a single voltage-dependent conductance mechanism underlies the depolarization-activated inward current in Y-79 cells. This channel appears to be primarily permeable to calcium, but with a significant contribution by sodium ions. Its functioning appears to be modulated by extracellular calcium.
Induction of voltage-dependent sodium channels by in vitro differentiation of human retinoblastoma cells
Authors: del Pilar Gomez M. , Waloga G. , Nasi E.
Published: December 2017

1. Neuronlike differentiation of Y-79 retinoblastoma was chemically induced in vitro, by plating the cells onto a poly-D-lysine and laminin substrate. The changes in voltage-dependent conductances after 48-72 h were examined with the whole-cell tight-seal and the perforated-patch recording techniques. 2. Although outward currents carried by potassium ions appeared qualitatively similar before and after differentiation, the depolarization-activated transient inward current displayed a pronounced acceleration of its activation and inactivation kinetics. 3. After differentiation, both the threshold of activation and the steady-state inactivation curve of the inward current are displaced in the negative direction by approximately 10-20 mV as compared with untreated cells. The current attains its peak amplitude in approximately 1 ms at maximum activating voltages, and decays within 3 ms. In contrast, in undifferentiated cells these values are on the order of 6 and 60 ms, respectively. The time to recover from inactivation is also shortened 20-fold in differentiated cells. 4. Unlike the mixed conductance of undifferentiated cells, which requires extracellular calcium, the inward current of the neuronlike differentiated cells is insensitive to manipulations of external calcium. Instead, it can be completely abolished in a reversible way by sodium removal or by micromolar concentrations of tetrodotoxin (TTX) in the bathing solution. As such, it resembles in all salient respects the voltage-dependent sodium conductance of nerve cells. 5. The fast sodium current expressed after neuronal differentiation is not the result of a progressive enhancement of an existing conductance, because no such component is discernible in undifferentiated cells. Moreover, recordings performed in cells at early stages of differentiation also failed to reveal the coexistence of the immature and the differentiated inward currents. 6. A possible account of the present observations is that the native inward current of undifferentiated Y-79 cells may correspond to a precursor form of the mature channel, and the observed developmental changes induced by chemical differentiation could be a consequence of progressive modification of the original channels, rather than expression of a separate class of proteins.
The rostral hypothalamus: an area for the integration of autonomic and sensory responsiveness
Authors: Lumb B. M. , Lovick T. A.
Published: December 2017

1. An investigation has been made of the effects of chemical stimulation of neurons in the rostral hypothalamus on cardiovascular and respiratory parameters and on a nociceptive viscerosomatic reflex (reflex activity recorded from a lumbar spinal nerve in response to electrical stimulation of visceral afferent fibers in the splanchnic nerve) in alphaxalone/alphadolone-anesthetised rats. 2. Neurons were stimulated by microinjection of DL-homocysteic acid (DLH) at ventromedial forebrain sites between 2 mm caudal and 3 mm rostral to bregma. Any changes were monitored in viscerosomatic reflex activity and in the rate and depth of respiration, arterial blood pressure, heart rate, and hindlimb muscle blood flow. 3. Viscero-somatic reflex activity was depressed to varying degrees after injection of DLH at 20/96 sites and this was always accompanied by some form of cardiovascular change. At 8 sites inhibition of the reflex was accompanied by a cardiovascular response that included an initial pressor response (type I response) and at the other 12 sites there was an initial depressor response (type II response). Injection of DLH at a further 30 sites evoked a depressor response and no change in viscerosomatic reflex activity and at the remaining 45 sites there was no detectable change in any of the variables measured. 4. The degree of inhibition evoked from type I sites (mean 90%) was significantly greater (P < 0.001) than that evoked from type II sites (mean 58%). Type I responses were only evoked from an extremely localized region in the rostral anterior hypothalamus that corresponds to the lateral area of the anterior hypothalamus.(ABSTRACT TRUNCATED AT 400 WORDS)