bluuebunny/crossref_metadata_2025 huggingface dataset:
Involvement of GABA and glycine in recurrent inhibition of spinal motoneurons
Authors: Schneider S. P. , Fyffe R. E.
Published: December 2017

1. Recurrent inhibitory postsynaptic potentials (IPSPs) were recorded intracellularly from chloride-loaded motoneurons in the isolated lumbar spinal cord of neonatal rats (day 5-day 12). This in vitro preparation exhibited an intact and functional recurrent inhibitory pathway that displayed characteristics previously described for this pathway in other species. 2. Although strychnine (1-5 microM) depressed the chloride-dependent recurrent synaptic potentials evoked by ventral root stimulation by 48.2 +/- 2.7% (mean +/- SE, n = 13), confirming that part of the recurrent IPSP is mediated by a glycinergic mechanism, in every case a residual strychnine-resistant synaptic potential was observed. 3. The gamma-aminobutyric acid (GABA) antagonist bicuculline, in low concentrations (2-10 microM), depressed the recurrent synaptic potentials in a dose-dependent manner by 27.0 +/- 4.3% (range 0-49%, n = 19). Application of bicuculline almost eliminated the strychnine-resistant component of the IPSP. However, in some motoneurons, a small synaptic potential remained after combined application of strychnine and bicuculline. 4. The selective antagonists of GABA uptake, (+/-)-nipecotic acid (1 mM) and guvacine (1 mM), increased the amplitude of recurrent synaptic potentials in 12 of 16 motoneurons by 37.2 +/- 7.2% (range 12.6-84.2%). 5. The excitatory amino acid antagonists kynurenic acid (1 mM), 6-cyano-7-nitroquinoxaline-2,3-dione [CNQX (10 microM)] and 6,7-dinitroquinoxaline-2,3-dione (10 microM) potentiated recurrent synaptic potentials in 5 of 7 motoneurons. However, CNQX (10-15 microM) in the presence of strychnine and bicuculline virtually abolished the synaptic potential remaining after application of the inhibitory amino acid antagonists. It is concluded that ventral root stimulation evokes a small excitatory amino acid-mediated synaptic potential in neonatal rat motoneurons. 6. An antidromic synaptic potential due to electrotonic coupling between motoneurons was unaffected by changes in membrane potential, chloride loading, or antagonists of glycine, GABA, excitatory amino acid, and acetylcholine receptors. 7. The results suggest that a major portion of the strychnine-resistant component of the IPSP is mediated by a GABAergic mechanism. It is concluded that both glycinergic and GABAergic mechanisms play a role in recurrent inhibition of motoneurons in the mammalian spinal cord. It is unknown whether these inhibitory amino acids are released by a single pool of Renshaw cells or by neurochemically distinct populations.
Inputs from regularly and irregularly discharging vestibular nerve afferents to secondary neurons in squirrel monkey vestibular nuclei. III. Correlation with vestibulospinal and vestibuloocular output pathways
Authors: Boyle R. , Goldberg J. M. , Highstein S. M.
Published: December 2017

1. A previous study measured the relative contributions made by regularly and irregularly discharging afferents to the monosynaptic vestibular nerve (Vi) input of individual secondary neurons located in and around the superior vestibular nucleus of barbiturate-anesthetized squirrel monkeys. Here, the analysis is extended to more caudal regions of the vestibular nuclei, which are a major source of both vestibuloocular and vestibulospinal pathways. As in the previous study, antidromic stimulation techniques are used to classify secondary neurons as oculomotor or spinal projecting. In addition, spinal-projecting neurons are distinguished by their descending pathways, their termination levels in the spinal cord, and their collateral projections to the IIIrd nucleus. 2. Monosynaptic excitatory postsynaptic potentials (EPSPs) were recorded intracellularly from secondary neurons as shocks of increasing strength were applied to Vi. Shocks were normalized in terms of the threshold (T) required to evoke field potentials in the vestibular nuclei. As shown previously, the relative contribution of irregular afferents to the total monosynaptic Vi input of each secondary neuron can be expressed as a %I index, the ratio (x100) of the relative sizes of the EPSPs evoked by shocks of 4 x T and 16 x T. 3. Antidromic stimulation was used to type secondary neurons as 1) medial vestibulospinal tract (MVST) cells projecting to spinal segments C1 or C6; 2) lateral vestibulospinal tract (LVST) cells projecting to C1, C6; or L1; 3) vestibulooculo-collic (VOC) cells projecting both to the IIIrd nucleus and by way of the MVST to C1 or C6; and 4) vestibuloocular (VOR) neurons projecting to the IIIrd nucleus but not to the spinal cord. Most of the neurons were located in the lateral vestibular nucleus (LV), including its dorsal (dLV) and ventral (vLV) divisions, and adjacent parts of the medial (MV) and descending nuclei (DV). Cells receiving quite different proportions of their direct inputs from regular and irregular afferents were intermingled in all regions explored. 4. LVST neurons are restricted to LV and DV and show a somatotopic organization. Those destined for the cervical and thoracic cord come from vLV, from a transition zone between vLV and DV, and to a lesser extent from dLV. Lumbar-projecting neurons are located more dorsally in dLV and more caudally in DV. MVST neurons reside in MV and in the vLV-DV transition zone.(ABSTRACT TRUNCATED AT 400 WORDS)
Serotonergic stretch receptors induce plateau properties in a crustacean motor neuron by a dual-conductance mechanism
Authors: Kiehn O. , Harris-Warrick R. M.
Published: December 2017

1. The mechanisms for induction of bistable plateau potential properties by a set of serotonergic/cholinergic peripheral stretch receptor cells [gastropyloric receptor (GPR) cells] were examined in the crab stomatogastric ganglion (STG) with the use of intracellular recording techniques. 2. GPR cell stimulation evoked nicotinic excitatory postsynaptic potentials (EPSPs) and induced plateau potential capability in the dorsal gastric (DG) motor neuron. The plateau potential could be triggered during a GPR train either by the summating nicotinic EPSPs or by brief intracellular current injection. After pharmacological blockade of nicotinic and muscarinic receptors, a slow depolarization in response to GPR stimulation was revealed. Prolonged plateau potentials could still be evoked after this treatment. Local application of serotonin (5-HT; 10 microM to 1 mM) mimicked the noncholinergic plateau inducing effects of GPR stimulation in the DG motor neuron. 3. The synergistic action of acetylcholine (ACh) and 5-HT was examined by stimulating the GPR cells at different frequencies (1-20 Hz). The plateau induction was present down to 2 Hz. The time to onset for triggering a plateau during a GPR train was determined by the co-released ACh. 4. The 5-HT-evoked slow depolarization persisted in tetrodotoxin (TTX; 0.1-1 microM), and the DG motor neuron could still produce a plateau potential on brief depolarization in the absence of the spike-generating mechanism. 5. In normal TTX-containing saline, the 5-HT-evoked depolarization was accompanied by a weak and variable decrease in apparent input conductance. After substituting one-half of the extracellular sodium with either Trisma-HCl or choline, the decrease in apparent input conductance became more pronounced. This decrease was converted to an increase in apparent input conductance when extracellular Ca2+ was replaced with Mg2+. 6. Under voltage-clamp conditions, local application of 5-HT caused a slow inward current of prolonged duration in DG. The current versus voltage relationship had an inverted U-shape with no apparent reversal potential in the entire voltage range investigated (-90 to -5 mV). The 5-HT-induced changes in input conductance showed a complex voltage dependence, with a conductance decrease from moderately depolarized voltages. 7. Extracellular Cs+ (2-4 mM) caused the DG to hyperpolarize 2-4 mV from rest, whereas lowering extracellular Ca2+ caused it to depolarize 7-15 mV. The combined action of low extracellular Ca2+ and 2-4 mM Cs+ caused an almost complete block of the slow 5-HT-evoked depolarization.(ABSTRACT TRUNCATED AT 400 WORDS)
Nucleus centralis of the amygdala and the globus pallidus ventralis: electrophysiological evidence for an involvement in pain processes
Authors: Bernard J. F. , Huang G. F. , Besson J. M.
Published: December 2017

1. Neurons (n = 177) were recorded with extracellular micropipettes in and around the nucleus centralis of the amygdala (Ce), in anesthetized rats. The spontaneous activity of these neurons was variable (0.25 less than 3 less than 35 Hz, n = 175; 10th percentile less than median less than 90th percentile). A majority (80%) of these neurons were excited or inhibited exclusively or preferentially by noxious stimuli. These units were separated into two groups: 1) a group of neurons excited by noxious stimuli (46% of the whole population) and 2) a group of neurons inhibited by noxious stimuli (34% of the whole population). 2. The receptive fields of both groups of neurons were very large: in about one-half the cases the neurons responded similarly from all parts of the body, and in the other cases the responses were greater when the stimuli were applied to a restricted part of the body. 3. Seventy-seven percent of the excited neurons had responses of relatively high magnitudes. In this group, most cells (75%) were exclusively driven by noxious stimuli; the others (25%) were preferentially activated by noxious stimuli. These neurons responded to mechanical (pinch or squeeze) and/or thermal (water bath or water jet greater than 44 degrees C) noxious stimuli with a marked and sustained activation. 4. Sixty percent of the inhibited neurons had a marked decrease of activity in response to noxious stimuli. In this group, most of them (81%) were exclusively inhibited by noxious stimuli, whereas the remainder (19%) were preferentially inhibited by noxious stimuli. These neurons responded to mechanical (pinch or squeeze) and/or thermal (water bath or waterjet greater than 44 degrees C) noxious stimuli with a suppression or a marked and sustained decrease in activity. 5. All of the nociceptive neurons responded to intense transcutaneous electrical stimulation with one or several components of activation or inhibition. According to their latencies, three types of components were distinguished: early, intermediate, and late components. We estimate that the early and the intermediate components would be triggered by the activity of peripheral fibers in the 6- to 20-m/s range and therefore could be in the A delta fibers range, whereas the late component would be triggered by fibers in the 0.5- to 1-m/s range and therefore could be in the C fibers range. 6. The neurons excited or inhibited by noxious stimuli were not homogeneously distributed in and around the Ce.(ABSTRACT TRUNCATED AT 400 WORDS)
Responsiveness and functional attributes of electrically localized terminals of cutaneous C-fibers in vivo and in vitro
Authors: Kress M. , Koltzenburg M. , Reeh P. W. , Handwerker H. O.
Published: December 2017

1. The purpose of the present study was to compare the responsiveness unmyelinated cutaneous units in vivo and in vitro and to determine the proportion of primary afferents innervating the rat hairy skin that do not respond to transient mechanical or thermal stimuli. We have adopted electrical search strategies to locate the terminal arborization of unmyelinated fibers before testing the sensitivity to adequate stimuli. 2. A total of 144 unmyelinated units were studied, of which 31 were obtained from in vivo and 113 from in vitro experiments. 55 afferents were investigated after chronic surgical sympathectomy. Units recorded from sympathectomized rats did not differ in their conduction velocity, electrical thresholds, or receptive properties from units in intact animals. 3. There were only minor differences between the properties of units recorded in vivo and in vitro. This probably reflects technical differences of the setups rather than biological changes introduced by the in vitro conditions. Except for a higher prevalence of mechano-cold sensitive units in vitro, there was no significant difference between the distributions of receptor types. 4. Eight of 31 units (26%) recorded in vivo and 17 of 113 units (15%) obtained from in vitro experiments failed to respond to transient mechanical or thermal stimuli. In vivo, one of eight initially unresponsive units was activated by repeated mechanical and thermal stimulation. Two further units became responsive after topical application of mustard oil. In vitro, 2 of 17 unresponsive units were activated by repeated stimulation. Ten of the remaining unresponsive units were treated with a combination of inflammatory mediators. Four of these units were activated: three developed ongoing activity, and two of them also became responsive to mechanical and/or heat stimuli. The fourth unit responded to probing but was not spontaneously active. 5. We conclude that transient mechanical or thermal stimuli can excite the majority of unmyelinated cutaneous units. However, in vivo and in vitro, part of unmyelinated units are initially unresponsive even to noxious forms of stimulation. Because those unresponsive units were also encountered in sympathectomized preparations, and because some units can be recruited with repeated noxious stimuli or inflammatory agents, it is unlikely that all of them are sympathetic efferents. The same substances that cause sensitization of "normal" nociceptors are capable of recruiting initially unresponsive unmyelinated afferents.
Pharmacological properties of N-methyl-D-aspartate receptors on ganglion cells of an amphibian retina
Authors: Gottesman J. , Miller R. F.
Published: December 2017

1. The pharmacological characteristics of the N-methyl-D-aspartate (NMDA) receptors on amphibian retinal ganglion cells were studied to determine their similarities or differences from NMDA receptors found in mammalian central nervous system (CNS) cells. Cells were tested with a variety of NMDA antagonists acting at sites on the NMDA receptor/ion channel complex. 2. Whole-cell voltage-clamp recordings were obtained from ganglion cells of the larval tiger salamander with a retinal slice preparation. All cells responded with inward currents (Vhold = -70 mV) when exposed to bath applications of NMDA, kainate (KA), and glutamate (GLU). NMDA currents reversed near 0 mV and showed a negative slope conductance region in the presence of external Mg2+. 3. NMDA-evoked inward currents could be blocked by application of 300 microM D-2-amino-7-phosphonoheptanoate (DAP7), 100 microM Zn2+, 25 microM 7-chloro-kynurenate (7-cl-KYN), 1 microM MK-801, and 5 mM Mg2+. These results indicate that like mammalian NMDA receptors the amphibian NMDA receptor possesses binding sites for NMDA, glycine, zinc, dissociative anesthetics, and Mg2+. 4. NMDA responses were evoked in the presence of 1 mM extracellular Mg2+ in 100% of cells tested when held at -70 mV. Furthermore, there was a resting conductance at -70 mV and membrane current noise that could be attenuated by the application of NMDA-specific antagonists suggesting a tonic activation of NMDA receptors for cells at the resting potential.
Endogenous adenosine contributes to hypoxic synaptic depression in hippocampus from young and aged rats
Authors: Gribkoff V. K. , Bauman L. A.
Published: December 2017

1. Extracellular field potentials were recorded to study the role of endogenous adenosine during hypoxia in area CA1 of rat hippocampal slices. 2. Hypoxic conditions, induced by 15 min exposure to 95% N2-5% CO2 at 32 degrees C and in high-glucose incubation medium, produced a rapid and reversible depression of evoked synaptic potentials. 3. In slices from young Sprague-Dawley rats, the hypoxia-induced synaptic depression was reduced in a concentration-dependent manner by the adenosine antagonist 8-cyclopentyltheophylline (8-CPT; 100 nM-2.0 microM). 4. Recovery of synaptic potentials after hypoxia was complete under each experimental condition. 5. Extended periods of hypoxia lasting 30 min likewise produced a rapid and near total suppression of the evoked synaptic potentials. In the presence of 8-CPT, both the population excitatory postsynaptic potential (EPSP) slope and population spike amplitude were significantly preserved throughout the hypoxic episode. 6. Neither the onset rate nor the degree of the hypoxia-induced synaptic depression were significantly different in slices from young, adult, or aged Fischer 344 rats. Reduction of the hypoxia-induced response depression by 8-CPT was also similar in all age groups. 7. These findings have further characterized the important involvement of endogenous adenosine in the potentially neuroprotective synaptic depression observed in hippocampal slices from young and aged rats during hypoxia.
A motor area rostral to the supplementary motor area (presupplementary motor area) in the monkey: neuronal activity during a learned motor task
Authors: Matsuzaka Y. , Aizawa H. , Tanji J.
Published: December 2017

1. The rostromesial agranular frontal cortex of macaque monkey (Macaca fuscata), traditionally defined as the supplementary motor area (SMA), was studied using various physiological techniques to delineate two different areas rostrocaudally. 2. Field and unitary responses to electrical stimulation of the primary motor cortex were distinct in the caudal part, but minimal or absent in the rostral part. Intracortical microstimulation readily evoked limb or orofacial movements in the caudal part, but only infrequently in the rostral part. Neuronal responses to visual stimuli prevailed in the rostral part, but somatosensory responses were rare. The opposite was true in the caudal part. 3. The rostral part, roughly corresponding to area 6a beta, was operationally defined as the presupplementary motor area (pre-SMA). The caudal part was redefined as the SMA proper. 4. Single-cell activity in the pre-SMA was quantitatively compared with that in the SMA proper in relation to a trained motor task. 5. Phasic responses to visual cue signals indicating the direction of forthcoming arm-reaching movement were more abundant in the pre-SMA. 6. Activity changes during the preparatory period, which lasted until the occurrence of the trigger signal for the reaching movement, were more frequent in the pre-SMA. 7. Phasic, movement-related activity was more frequent in the SMA, and its onset was often time locked to the movement onset. In the pre-SMA, the occurrences of response time locked to the movement-trigger signal were more frequent than in the SMA. 8. Among neurons in both areas, directional selectivity was found in all the cue, preparatory, and movement-related responses.
The action of the putative neurotransmitters N-acetylaspartylglutamate and L-homocysteate in cat dorsal lateral geniculate nucleus
Authors: Jones H. E. , Sillito A. M.
Published: December 2017

1. We have examined the actions and pharmacology of two putative optic nerve transmitters, N-acetylaspartylglutamate (NAAG) and L-homocysteic acid (L-HCA), in the feline dorsal lateral geniculate nucleus (dLGN). We compared the responses obtained to iontophoretic application of these substances with those elicited by visual stimulation and application of specific N-methyl-D-aspartate (NMDA) and non-NMDA receptor agonists. The relative effects of the selective NMDA antagonist 3-[(+/-)-2-carboxypiperazin-4-yl]-propyl-1-phosphonic acid (CPP) and the selective non-NMDA antagonist 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX) were tested on these responses. 2. There was a pronounced contrast between the influence of iontophoretically applied NAAG and L-HCA on dLGN cells. Iontophoretic application of NAAG [ejection current range 75–200 nA (mean 125 nA)] evoked either no effect (17/37), or very weak and sluggish excitatory (16/37) or inhibitory (4/37) effects. Conversely, L-HCA application [current range 25–136 nA (mean 67 nA)] elicited brisk and powerful excitatory responses (32/32) that were comparable with those produced by visual stimulation and iontophoresis of NMDA, kainate, and alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA). 3. Responses to L-HCA were selectively antagonized by application of the NMDA receptor antagonist CPP but were generally much less affected by the non-NMDA receptor antagonist CNQX. The weak and inconsistent responses to NAAG were not compatible with an evaluation of antagonist effects. 4. CPP application at dose levels selective for NMDA with respect to kainate and AMPA did not exert equal effects on L-HCA and NMDA. Whereas the mean responses to L-HCA were reduced to 32% of control for Y cells and 21% for X cells, those to NMDA were 11 and 11%, respectively. However, the level of reduction of the visual response for X and Y cells was very similar to that of L-HCA, visual responses being reduced to 35 and 22% of control for Y and X cells. 5. CNQX application reduced the visual response level of Y cells to 64% of control and that of X cells to 65%. The mean level for the L-HCA response of Y cells was 106% of control; the mean for X cells, 79%, was substantially below control. The responses to kainate and AMPA were reduced to a much greater extent. 6. The data suggest that it is unlikely that NAAG is the optic nerve transmitter.(ABSTRACT TRUNCATED AT 400 WORDS)
Action of brain stem reticular afferents on lagged and nonlagged cells in the cat lateral geniculate nucleus
Authors: Humphrey A. L. , Saul A. B.
Published: December 2017

1. The A-laminae of the cat lateral geniculate nucleus (LGN) contain two distinct groups of relay neurons: lagged and nonlagged cells. The groups differ in the pattern, timing, and amplitude of response to flashing spots. At spot onset, nonlagged cells discharge at short latency with an excitatory transient; in lagged cells this transient is supplanted by an inhibitory dip and a delayed latency to discharge. At spot offset, lagged cell discharge decays more slowly than in nonlagged cells. Here we have investigated the facilitatory influence of the brain stem reticular formation on the response properties of lagged X-cells (XL) and nonlagged X- and Y-cells (XN and YN). We were particularly interested in whether the inhibitory dip and sluggish response of lagged cells could be reversed during brain stem activation and the cells induced to respond like nonlagged cells. The peribrachial region (PB) of the pontine reticular formation was stimulated electrically with the use of 1,100-ms-long pulse trains that were paired with flashing spot stimuli. 2. Stimulation of PB led to an increase in the amplitude of visually evoked discharge in lagged and nonlagged cells. Compared with their response to spot stimulation alone, the average PB-evoked increase in mean discharge rate was greater than 50% in both groups. The mean discharge rate during PB plus spot stimulation was somewhat higher for XN-cells than for YN- and XL-cells, reflecting the relatively higher discharge rate among XN-cells during spot stimulation alone. 3. Two measures of response timing characterize lagged and nonlagged cells: latency to half-maximal discharge at spot onset (half rise) and latency to half-minimal discharge at spot offset (half fall). Among XN- and YN-cells, PB stimulation had no significant effect on these two latencies; among XL-cells, both latencies were reduced by 43 and 35%, respectively, on average. 4. During spot stimulation alone, all lagged cells were distinguishable from all nonlagged cells in having half-rise and half-fall latencies greater than 60 ms. Despite the reduction among XL-cells in these 2 latencies during PB stimulation, all but 2 of the 40 XL-cells maintained laggedlike latencies. The majority (95%) of XL-cells remained unambiguously lagged on these measures during brain stem stimulation. 5. During spot stimulation alone, 30 of 40 XL-cells tested displayed a prominent and often long-lasting inhibitory dip in discharge starting approximately 45 ms after spot onset. During PB stimulation only three cells lost the dip.(ABSTRACT TRUNCATED AT 400 WORDS)
Expression of the mRNAs for the Kv3.1 potassium channel gene in the adult and developing rat brain
Authors: Perney T. M. , Marshall J. , Martin K. A. , Hockfield S. , Kaczmarek L. K.
Published: December 2017

1. The gene for a mammalian Shaw K+ channel has recently been cloned and has been shown, by alternative splicing, to give rise to two different transcripts, Kv3.1 alpha and Kv3.1 beta. To determine whether these channels are associated with specific types of neurons and to determine whether or not the alternately spliced K+ channel variants are differentially expressed, we used ribonuclease (RNase) protection assays and in situ hybridization histochemistry to localize the specific subsets of neurons containing Kv3.1 alpha and Kv3.1 beta mRNAs in the adult and developing rat brain. 2. In situ hybridization histochemistry revealed a heterogeneous expression pattern of Kv3.1 alpha mRNA in the adult rat brain. Highest Kv3.1 alpha mRNA levels were expressed in the cerebellum. High levels of hybridization were also detected in the globus pallidus, subthalamus, and substantia nigra reticulata. Many thalamic nuclei, but in particular the reticular thalamic nucleus, hybridized well to Kv3.1 alpha-specific probes. A subpopulation of cells in the cortex and hippocampus, which by their distribution and number may represent interneurons, were also found to contain high levels of Kv3.1 alpha mRNA. In the brain stem, many nuclei, including the inferior colliculus and the cochlear and vestibular nuclei, also express Kv3.1 alpha mRNA. Low or undetectable levels of Kv3.1 alpha mRNA were found in the caudate-putamen, olfactory tubercle, amygdala, and hypothalamus. 3. Kv3.1 beta mRNA was also detected in the adult rat brain by both RNase protection assays and by in situ hybridization experiments. Although the beta splice variant is expressed at lower levels than the alpha species, the overall expression pattern for both mRNAs is similar, indicating that both splice variants co-expressed in the same neurons. 4. The expression of Kv3.1 alpha and Kv3.1 beta transcripts was examined throughout development. Kv3.1 alpha mRNA is detected as early as embryonic day 17 and then increases gradually until approximately postnatal day 10, when there is a large increase in the amount of Kv3.1 alpha mRNA. Interestingly, the expression of Kv3.1 beta mRNA only increases gradually during the developmental time frame examined. Densitometric measurements indicated that Kv3.1 alpha is the predominant splice variant found in neurons of the adult brain, whereas Kv3.1 beta appears to be the predominant species in embryonic and perinatal neurons. 5. Most of the neurons that express the Kv3.1 transcripts have been characterized electrophysiologically to have narrow action potentials and display high-frequency firing rates with little or no spike adaptation.(ABSTRACT TRUNCATED AT 400 WORDS)
Mechanical response of frog saccular hair bundles to the aminoglycoside block of mechanoelectrical transduction
Authors: Denk W. , Keolian R. M. , Webb W. W.
Published: December 2017

1. Deflections of the mechanosensory hair bundles on frog saccular hair cells were measured interferometrically, with submillisecond temporal and submicrometer spatial resolution, and with subnanometer displacement sensitivity. 2. The direction of the initial bundle deflection (toward the taller stereocilia) in response to a sudden application of aminoglycoside antibiotics shows that the mechanosensory channels are blocked in their mechanically open state. 3. The magnitude of the initial deflection is consistent with published data on the gating swing as derived from the gating compliance. 4. A delayed relaxation and frequently a reversal of the initial deflection were observed and are attributed to the previously reported mechanical adaptation mechanism, which is at least partially controlled by the influx of Ca2+ through the transduction channels. 5. Increases of low-frequency spontaneous motion were found at intermediate blocker concentrations. They can be well accounted for by the fluctuating force exerted on the bundle by the random binding and unbinding of blocker molecules. 6. The mechanical response of the hair bundle to aminoglycosides may be related to their acute and specific ototoxicity.
Bursting and tonic discharges in two classes of reticular thalamic neurons
Authors: Contreras D. , Curro Dossi R. , Steriade M.
Published: December 2017

1. Two types of cat reticular (RE) thalamic cells were disclosed by means of intracellular recordings under urethan anesthesia. The RE neurons were identified by their typical depolarizing spindle oscillations in response to synchronous stimulation of the internal capsule. 2. In type I neurons (n = 41), depolarizing current pulses induced tonic firing at the resting or slightly depolarized membrane potential (Vm) and triggered high-frequency spike bursts at a Vm more negative than -75 mV. As well, these cells discharged rebound bursts at the break of a hyperpolarizing current pulse. Internal capsule stimulation elicited spindle sequences made off by depolarizing waves giving rise to spike bursts. 3. Type II cells (n = 9) did not discharge spike bursts to large depolarizing current pulses even when the Vm reached -100 mV, nor did they fire rebound bursts after long-lasting hyperpolarizing current pulses or spike bursts riding on the rhythmic depolarizing components of spindle sequences. 4. Compared with type I cells, type II cells showed less frequency accommodation during tonic firing. The latter neuronal class discharged at high frequencies (40 Hz) with slight DC depolarization, approximately 8-10 Hz at the resting Vm, and no underlying synaptic or subthreshold oscillatory events could be detected when the firing was blocked by DC hyperpolarization. 5. The presence of two cell classes in the RE nucleus challenges the common view that this nucleus consists of a single neuronal class. We suggest that a different set of conductances is present in type II RE neurons, thus preventing the low-threshold Ca2+ current from dominating the behavior of these cells.
Modulation of IK,Ca by phorbol ester-mediated activation of PKC in pleural sensory neurons of Aplysia
Authors: Critz S. D. , Byrne J. H.
Published: December 2017

1. The electrophysiological properties of the sensory neurons that mediate withdrawal reflexes in Aplysia are modulated by a number of second messengers. For example, the second messengers adenosine 3',5'-cyclic monophosphate (cAMP) and arachidonic acid modulate the S-K+ current (IK,S) and the calcium-activated K+ current (IK,Ca). Recent evidence suggests that protein kinase C (PKC) may also be an important regulator of cellular plasticity. In the present study we examined the possibility that IK,Ca was modulated by the activation of PKC in the pleural sensory neurons. 2. In voltage-clamped sensory neurons the application of phorbol esters, such as phorbol dibutyrate (PDBu), phorbol myristate (PMA), and phorbol diacetate (PDAc), which activate PKC, caused a dose-dependent increase in a voltage-dependent current with properties that resembled IK,Ca. The inactive isomer of phorbol ester, 4 alpha-phorbol, was without effect. 3. This phorbol ester-sensitive current had the kinetics and pharmacological sensitivity of IK,Ca. The current developed slowly during step depolarizations, showed little inactivation, and was activated at membrane potentials greater than approximately 0 mV. In addition, the current modulated by phorbol esters was blocked by a concentration of tetraethylammonium (TEA) that blocks a component of IK,Ca in the sensory neurons. 4. IK,Ca, which was activated directly by the iontophoretic injection of Ca2+, was also enhanced by PDBu. Moreover, the enhancement of Ca(2+)-elicited responses by PDBu persisted after Ca2+ influx was blocked by cobalt. These results indicate that at least one component of the modulation of IK,Ca by PDBu was independent of the modulation of voltage-dependent Ca2+ channels.(ABSTRACT TRUNCATED AT 250 WORDS)
Mu opioid receptor-mediated modulation of synaptic currents in dentate granule cells of rat hippocampus
Authors: Xie C. W. , Morrisett R. A. , Lewis D. V.
Published: December 2017

1. The effect of a selective mu opioid agonist, [N-MePhe3-D-Pro4]morphiceptin (PL017), on synaptic transmission in the dentate gyrus was examined in hippocampal slices. Synaptic currents were evoked by stimulation of the outer molecular layer and recorded from granule cells using whole-cell voltage-clamp techniques. 2. Monosynaptic inhibitory postsynaptic currents (IPSCs) were evoked in the presence of D(-)-2-amino-5-phosphonovaleric acid (D-APV), and N-methyl-D-aspartate (NMDA) receptor antagonist, and 6,7-dinitroquinoxaline-2,3-dione (DNQX), a non-NMDA type of glutamate receptor antagonist. The IPSCs consisted of a gamma-aminobutyric acid (GABA)A receptor-mediated early component and a GABAB receptor-mediated late component. 3. Bath application of PL017 (0.3-3 microM) induced a dose-dependent reduction in the amplitude of both early IPSCs (21-56%) and late IPSCs (43-81%). These effects could be reversed by the opiate antagonist naloxone (1 microM) or prevented by the selective mu antagonist beta-funaltrexamine hydrochloride (10 microM). 4. NMDA receptor-mediated excitatory postsynaptic currents (EPSCs) were revealed in the presence of DNQX and the GABAA antagonist bicuculline methiodide. PL017 (3 microM) caused a 35% reduction in the amplitude of NMDA EPSCs. NMDA receptor-mediated population EPSPs recorded extracellularly were also inhibited by 3 microM PL017 to a similar degree. 5. Non-NMDA receptor-mediated EPSCs were demonstrated in the presence of D-APV and bicuculline methiodide. The amplitude of non-NMDA EPSCs was not affected by PL017.(ABSTRACT TRUNCATED AT 250 WORDS)
Voltage-dependent ionic currents in solitary horizontal cells isolated from cat retina
Authors: Ueda Y. , Kaneko A. , Kaneda M.
Published: December 2017

1. Horizontal cells of the cat retina were isolated by enzymatic dissociation. Two types of horizontal cells were identified: the axonless (A-type) horizontal cell having four to six thick, long (approximately 100 microns) dendrites, and the short-axon (B-type) horizontal cell having many (> 5) fine, short (approximately 30 microns) dendrites. 2. Membrane properties of isolated horizontal cells were analyzed under current-clamp and voltage-clamp conditions. In the A-type cell, the average resting potential was -55 mV and the mean membrane capacitance was 110 pF, whereas values in the B-type cell were -58 mV and 40 pF, respectively. The A-type cell showed long-lasting Ca spikes, but B-type cells had no Ca spikes. 3. Five types of voltage-dependent ionic currents were recorded: a sodium current (INa), a calcium current (ICa), and three types of potassium currents. Potassium currents consisted of potassium current through the inward rectifier (Ianomal), transient outward potassium current (IA), and potassium current through the delayed rectifier (IK(v)). INa was recorded only from A-type cells. Other currents were recorded from both types of cells. 4. INa activated when cells were depolarized from a holding potential (Vh) of -95 mV, and it was maximal at -25 mV. This current was blocked by tetrodotoxin. Approximately half of the A-type cells had INa, but no B-type cell had this current. 5. L-type ICa, an inward-going sustained current, was activated with depolarization more positive than -25 mV. Current amplitude reached a maximal value near 15 mV and became smaller with further depolarization.(ABSTRACT TRUNCATED AT 250 WORDS)
Axonal cross-excitation in nerve-end neuromas: comparison of A- and C-fibers
Authors: Amir R. , Devor M.
Published: December 2017

1. We recorded from single afferent axons ending in chronic sciatic nerve end neuromas in rats with the use of the teased-fiber method. Axons were sought that had ongoing impulse discharge originating in the neuroma. 2. Recording from myelinated (A-) fibers, tetanic stimulation of neighboring axons (50 Hz, 5 or 10 s, intensity adequate to drive A-fibers) caused an increase, and sometimes a decrease, in the rate of ongoing discharge in 68% of the fibers tested. In addition, some initially silent neuroma A-fibers (1.4%) were activated in this way. Both A beta and A delta fibers responded, although the likelihood of response was greater in A beta fibers. We call this form of interfiber cross-excitation "crossed afterdischarge." 3. In contrast to A-fibers, crossed afterdischarge was evoked with these stimulation parameters in < or = 5% of the spontaneously active unmyelinated (C-) fibers sampled. No initially silent C-fibers were activated. 4. C-fibers remained largely insensitive to cross-excitation by neighboring axons even when the strength of stimulus pulses was increased so as to include neighboring A + C-fibers. 5. The difference between A- and C-fibers could not be accounted for on the basis of the maturity of the neuroma, rate and pattern of ongoing discharge, or use of Flaxedil paralysis. 6. The difference between A- and C-fibers is discussed in terms of two alternative mechanisms that may underlie crossed afterdischarge: mediation by a neurotransmitter(s) in a nonsynaptic mode, and mutual K+ depolarization.(ABSTRACT TRUNCATED AT 250 WORDS)
Visual response latencies in striate cortex of the macaque monkey
Authors: Maunsell J. H. , Gibson J. R.
Published: December 2017

1. Many lines of evidence suggest that signals relayed by the magnocellular and parvocellular subdivisions of the primate lateral geniculate nucleus (LGN) maintain their segregation in cortical processing. We have examined two response properties of units in the striate cortex of macaque monkeys, latency and transience, with the goal of assessing whether they might be used to infer specific geniculate contributions. Recordings were made from 298 isolated units and 1,129 multiunit sites in the striate cortex in four monkeys. Excitotoxin lesions that selectively affected one or the other LGN subdivision were made in three animals to demonstrate directly the magnocellular and parvocellular contributions. An additional 435 single units and 551 multiunit sites were recorded after the ablations. 2. Most units in striate cortex had visual response latencies in the range of 30-50 ms under the stimulus conditions used. The earliest neuronal responses in striate cortex differed appreciably between individuals. The shortest latency recorded in the four animals ranged from 20 to 31 ms. Comparable values were obtained from both single unit and multiunit sites. After lesions were made in the magnocellular subdivision of the LGN in two animals, the shortest response latencies were 7 and 10 ms later than before the ablations. A larger lesion in the parvocellular subdivision of another animal produced no such shift. Thus it appears that the first 7-10 ms of cortical activation can be attributed to activation relayed by the magnocellular layers of the LGN. 3. The units with the shortest latencies were all found in layers 4C or 6 and their responses were among the most transient in striate cortex. Furthermore, their responses all showed a pronounced periodicity at a frequency of 50-100 Hz. This periodicity was stimulus locked, and the responses of all short-latency units oscillated in phase. 4. An index of response transience was computed for the units recorded in striate cortex. The distribution of this index was unimodal and gave no suggestion of distinct contributions from the geniculate subdivisions. Magnocellular and the parvocellular lesions affected the overall transience of responses in striate cortex. The changes, however, were very small; extremely transient responses and extremely sustained responses survived both types of lesions. 5. A characteristic profile was observed in the response latencies in superficial layers. Latencies appeared to increase monotonically from layer 4 toward the surface of cortex, with the most superficial neurons not becoming active until 15 ms after responses were observed in layer 4C.(ABSTRACT TRUNCATED AT 400 WORDS)
Flow of excitation within rat barrel cortex on striking a single vibrissa
Authors: Armstrong-James M. , Fox K. , Das-Gupta A.
Published: December 2017

1. Extracellular spike recordings were made from single cells in various layers of barrel cortex in adult rats anesthetized with urethan. Response magnitude and latency differences to brief 1.14 degrees deflections of mystacial vibrissae of center (principal) and surround receptive-field vibrissae were measured. Latency differences for pairs of cells in the same penetration to stimulation of the principal vibrissa were also collected. In separate experiments the domains of layer IV cells were mapped for their influence by a single vibrissa and their latencies to this vibrissa were recorded. In all experiments precise locations of layer IV cells in each penetration were identified using dye-lesioning and cytochrome oxidase staining of tangential sections. 2. The results suggest that principal vibrissa data are relayed radially in a column of neurons before parallel relay to adjacent columns. To the principal vibrissa, layers IV and Vb neurons discharged earliest, with layers II and III on average 2 and 3 ms later, respectively. Serial relay from layers IV to III to II was suggested to be the most common event. Although layer Va cells fired next, a single-column organization is not suggested for them because differences in latency or response magnitude to their principal and immediate surround vibrissae were not significant. Layer II, III and IV cells showed no statistical difference in latency to the nearest surround vibrissa but fired significantly later than to their principal input. 3. Because, from our previous studies, surround receptive fields of barrel cells in rat S1 cortex appear to be constructed intracortically, these data suggest a parallel column-column relay for their construction. Horizontal relay between barrels occurred first within the septae between barrels. Mean intracortical transmission velocities were calculated at approximately 0.05 m/s for column-column information transfer.
Simulation of the currents involved in rhythmic oscillations in thalamic relay neurons
Authors: Huguenard J. R. , McCormick D. A.
Published: December 2017

1. To perform simulations of the various modes of action potential generation in thalamic relay neurons, we developed Hodgkin-and-Huxley style mathematical equations that describe the voltage dependence and kinetics of activation and inactivation of four different currents, including the transient, low-voltage-activated Ca2+ current (IT), the rapidly inactivating transient K+ current (IA), the slowly inactivating K+ current (IK2), and the hyperpolarization-activated, mixed cationic current (Ih). The modeled currents were derived either from acutely dissociated rat thalamic relay neurons (IT, IA, IK2), or from guinea pig thalamic relay cells maintained in slices in vitro (Ih). 2. The voltage dependence of steady-state activation and inactivation of IT, IA, and IK2 and the activation of Ih could be modeled with Boltzmann-style equations. Modeling of the behavior of IT to depolarizing steps in voltage clamp required the use of the constant field equation to relate permeability to T-current amplitude. The time constant of activation of IT was described by a continuous bell-shaped function with a maximum near 15 ms at threshold for activation (-75 mV) and 23 degrees C. Mathematical description of the kinetics of inactivation and removal of inactivation of this current required two separate functions. 3. The rapidly activating and inactivating K+ current IA was modeled by assuming two components with different time constants of inactivation. The kinetics of activation was described as a continuous function of voltage with the slowest time constant, near 2.5 ms, at threshold for activation (-60 mV) and 23 degrees C. In contrast, the kinetics of inactivation of both components were described as voltage independent, consistent with experimental data. The rate or removal of inactivation of both components of IA was described as continuously increasing with the degree of hyperpolarization. 4. The slowly inactivating K+ current IK2 was also modeled by assuming two components with different rates of inactivation. The kinetics of activation were described by a bell-shaped function with a maximum time constant near 80 ms at -40 mV and 23 degrees C, whereas threshold for activation was approximately -60 mV. Inactivation of both components was modeled as relatively independent of voltage, whereas removal of inactivation was described as a continuous function of membrane potential. 5. The hyperpolarization-activation cationic current, Ih, was modeled by assuming that the current activates with a single exponential relation and does not inactivate.(ABSTRACT TRUNCATED AT 400 WORDS)
Interpretation of time constant and electrotonic length estimates in multicylinder or branched neuronal structures
Authors: Holmes W. R. , Segev I. , Rall W.
Published: December 2017

1. We have investigated the theoretical and practical problems associated with the interpretation of time constants and the estimation of electrotonic length with equivalent cylinder formulas for neurons best represented as multiple cylinders or branched structures. Two analytic methods were used to compute the time constants and coefficients of passive voltage transients (and time constants of current transients under voltage clamp). One method, suitable for simple geometries, involves analytic solutions to boundary value problems. The other, suitable for neurons of any geometric complexity, is an algebraic approach based on compartmental models. Neither of these methods requires the simulation of transients. 2. We computed the time constants and coefficients of voltage transients for several hypothetical neurons and also for a spinal motoneuron whose morphology was characterized from serial reconstructions. These time constants and coefficients were used to generate voltage transients. Then exponential peeling, nonlinear regression, and transform methods were applied to these transients to test how well these procedures estimate the underlying time constants and coefficients. 3. For a serially reconstructed motoneuron with 732 compartments, we found that the theoretical and peeled tau 0 values were nearly equal, but the theoretical tau 1 was much larger than the peeled tau 1. The theoretical tau 1 could not be peeled because it was associated with a coefficient, C1, that had a very small value. In fact, there were 156 time constants between 1.0 and 6.0 ms, most of which had very small coefficients; none had a coefficient larger than 2% of the signal. The peeled value of tau 1 (called tau 1 peel) can be viewed as some sort of a weighted average of the time constants having the largest coefficients. 4. We studied simple hypothetical neurons to determine what interpretation could be applied to the multitude of theoretical time constants. We found that after tau 0, there was a group of time constants associated with eigenfunctions that were odd (or approximately odd) functions with respect to the soma. These time constants could be interpreted as "equalizing" time constants along particular paths between different pairs of dendritic terminals in the neuron. After this group of time constants, there was one that we call tau even because it was associated with an eigen-function that was approximately even with respect to the soma. This tau even could be interpreted as an equalizing time constant for charge equalization between proximal membrane (soma and proximal dendrites) and distal membrane (including all distal dendrites).4=