bluuebunny/crossref_metadata_2025 huggingface dataset:
Differential Epilepsy-Associated Alterations in Postsynaptic GABAA Receptor Function in Dentate Granule and CA1 Neurons
Authors: Gibbs John W. , Shumate Melissa D. , Coulter Douglas A.
Published: December 2017

Gibbs, John W., III, Melissa D. Shumate, and Douglas A. Coulter. Differential epilepsy-associated alterations in postsynaptic GABAA receptor function in dentate granule and CA1 neurons. J. Neurophysiol. 77: 1924–1938, 1997. Alterations in GABAergic function associated with the development of temporal lobe epilepsy (TLE) were examined with the use of patch-clamp recording techniques in dentate granule (DG) and CA1 neurons acutely isolated from control and spontaneously epileptic rats in which TLE was elicited by pilocarpine injection 3–17 wk before use. The maximal efficacy of γ-aminobutyric acid (GABA) in activating whole cell GABA currents increased significantly in epileptic DG neurons relative to controls. This efficacy increase was due to a 78% enhancement in the functional capacitance-normalized GABAA receptor (GABAAR) current density in epileptic DG neurons. Increased DG GABAAR current density was not accompanied by alterations in GABA potency (EC50). However, the maximal sensitivity of DG GABA-evoked currents to blockade by zinc increased 190% in epileptic neurons. Augmentation of epileptic DG neuron GABA-evoked currents by the broad-spectrum anticonvulsant benzodiazepine clonazepam (100 nM) was enhanced 114% relative to controls, whereas augmentation by the benzodiazepine1 (BZ1)-selective agonist zolpidem (100 nM) was decreased by 66%. In contrast to DG neurons, maximal efficacy of GABA in activating GABA currents decreased in epileptic CA1 neurons relative to controls, due to a 52% decrease in functional capacitance-normalized GABAAR current density. This altered efficacy of GABA was accompanied by an increased GABA potency (GABA EC50 was 35.8 and 24.5 μM in control and epileptic neurons, respectively). Sensitivity of GABA-evoked currents to blockade by zinc was unchanged in epileptic CA1 neurons, whereas clonazepam (100 nM) augmentation of CA1 GABA-evoked currents decreased 81% relative to controls. These regionally distinct epilepsy-associated modifications in hippocampal GABAergic function may be due to discrete structural alterations in postsynaptic GABAARs accompanying epileptogenesis, could be therapeutically important, and undoubtedly could contribute to the enhanced limbic excitability underlying TLE.
Spatially Organized Response Zones in Rat Olfactory Epithelium
Authors: Scott John W. , Shannon Donna E. , Charpentier Jeff , Davis Lisa M. , Kaplan Craig
Published: December 2017

Scott, John W., Donna E. Shannon, Jeff Charpentier, Lisa M. Davis, and Craig Kaplan. Spatially organized response zones in rat olfactory epithelium. J. Neurophysiol. 77: 1950–1962, 1997. Electroolfactogram recordings were made with a four-electrode assembly from the olfactory epithelium overlying the endoturbinate bones facing the nasal septum. In this study we tested whether odors of different chemical structures produce maximal responses along longitudinally oriented regions following the olfactory receptor gene expression zones described in the literature. The distribution of responses along the dorsal-to-ventral direction of this epithelium (i.e., across the expression zones) was tested in two types of experiments. In one, four electrodes were fixed along the dorsal-to-ventral axis of one turbinate bone. In the other, four electrodes were placed in corresponding positions on four turbinate bones and moved together up toward the top of the bone. These experiments compared the odorants limonene and α-terpinene, which are simple hydrocarbons, with carvone and menthone, which differ from the hydrocarbons by the presence of ketone groups. All responses were standardized to an amyl acetate or ethyl butyrate standard. The responses to limonene and α-terpinene were often larger for the ventral electrodes. The responses to carvone and menthone were largest for the dorsal electrodes. Intermediate electrodes gave responses that were intermediate in amplitude for these odors. The possibility that direction of air flow caused the observed response distributions was directly tested in experiments with odor nozzles placed in two positions. The relatively larger dorsal responses to carvone and relatively larger ventral responses to limonene were present despite odor nozzle position. We conclude that the responses to this set of odors vary systematically in a fashion parallel to the four gene expression zones. The odorant property that governs this response distribution may be related to the presence of oxygen-containing functional groups. Certain odors evoked larger responses at the intermediate electrode sites than at other sites. Cineole was the best example of this effect. This observation shows that not all oxygen-containing functional groups produce the same effect. Although we cannot exclude other possible mechanisms, these three response gradients may be produced by the four receptor expression zones described for many of the putative olfactory receptor genes. Therefore many of the receptors in each zone may share common properties. It remains to be determined whether this zonal input is significant in central odor processing. However, the correlation of odor chemical properties with the structure of receptor molecules in each zone may provide significant leads to structure-function relationships in vertebrate olfaction.
Speed of Ca2+Channel Modulation by Neurotransmitters in Rat Sympathetic Neurons
Authors: Zhou Jiuying , Shapiro Mark S. , Hille Bertil
Published: December 2017

Zhou, Jiuying, Mark S. Shapiro, and Bertil Hille. Speed of Ca2+channel modulation by neurotransmitters in rat sympathetic neurons. J. Neurophysiol. 77: 2040–2048, 1997. We have measured the onset and recovery speed of inhibition of N-type Ca2+channels in adult rat superior cervical ganglion neurons by somatostatin (SS), norepinephrine (NE), and oxotremorine-M (oxo-M, a muscarinic agonist), using the whole cell configuration of the patch-clamp method with 5 mM external Ca2+. With a local perfusion pipette system that changed the solution surrounding the cell within 50 ms, we applied agonists at various times before a brief depolarization from −80 mV that elicited ICa. At concentrations that produced maximal inhibition, the onset time constants for membrane-delimited inhibition by SS (0.5 μM), NE (10 μM), and oxo-M (20 μM) were 2.1, 0.7, and 1.0 s, respectively. The time constants for NE inhibition depended only weakly on the concentration, ranging from 1.2 to 0.4 s in the concentration range from 0.5 to 100 μM. Inhibition by oxo-M (20 μM) through a different G-protein pathway that uses a diffusible cytoplasmic messenger had a time constant near 9 s. The recovery rate constant from membrane-delimited inhibition was between 0.09 and 0.18 s−1, significantly higher than the intrinsic GTPase rate of purified G protein Go, suggesting that Ca2+channels or other proteins in the plasma membrane act as GTPase activating proteins. We also measured the rate of channel reinhibition after relief by strong depolarizing prepulses, which should reflect the kinetics of final steps in the inhibition process. In the presence of different concentrations of NE, reinhibition was four to seven times faster than the onset of inhibition, indicating that the slowest step of inhibition must precede the binding of G protein to the channel. We propose a kinetic model for the membrane-delimited NE inhibition of Ca2+channels. It postulates two populations of receptors with different affinities for NE, a single population of G proteins, and a single population of Ca2+channels. This model closely simulated the time courses of onset and recovery of inhibition and reinhibition, as well as the dose-response curve for inhibition of Ca2+channels by NE.
Sharpening of Frequency Tuning by Inhibition in the Thalamic Auditory Nucleus of the Mustached Bat
Authors: Suga Nobuo , Zhang Yunfeng , Yan Jun
Published: December 2017

Suga, N., Y. Zhang, and J. Yan. Sharpening of frequency tuning by inhibition in the thalamic auditory nucleus of the mustached bat. J. Neurophysiol. 77: 2098–2114, 1997. Unlike the quasitriangular frequency-tuning curves of peripheral neurons, pencil- or spindle-shaped frequency-tuning curves (excitatory areas) have been found in the central auditory systems of many species of animals belonging to different classes. Inhibitory tuning curves (areas) are commonly found on both sides of such “level-tolerant” sharp frequency-tuning curves. However, it has not yet been examined whether sharpening of frequency tuning takes place in the medial geniculate body (MGB). We injected an inhibitory transmitter antagonist, bicuculline methiodide (BMI), into the MGB of the mustached bat to examine whether frequency tuning is sharpened by inhibition in the MGB and whether this sharpening, if any, occurs in addition to that performed in prethalamic auditory nuclei. Thirty-seven percent of thalamic Doppler-shifted constant frequency (DSCF) neurons mostly showing a level-tolerant frequency-tuning curve had an inhibitory area or areas. BMI changed the inhibitory areas of these neurons into excitatory areas, so that their excitatory frequency-tuning curves became broader. However, the BMI-broadened excitatory frequency-tuning curves were still much narrower than those of peripheral neurons. Our results indicate that level-tolerant frequency tuning of thalamic DSCF neurons is mostly created by prethalamic auditory nuclei and that it is further sharpened in 37% of thalamic DSCF neurons by lateral inhibition occurring in the MGB. The comparisons in sharpness (quality factors) of frequency-tuning curves between peripheral, thalamic, and cortical DSCF neurons indicate that the skirt portion of tuning curves is sharper in the above order, and that their tip portion is not significantly different between the peripheral and thalamic DSCF neurons, but significantly sharper in the cortical DSCF neurons than in the thalamic DSCF neurons. Therefore the central auditory system has inhibitory mechanisms for the progressive sharpening of frequency tuning. DSCF neurons in the primary auditory cortex were recently found to show facilitative responses to paired sounds. That is, they are combination sensitive. In the present studies, we found that thalamic DSCF neurons also showed facilitative responses to paired sounds. The responses of thalamic DSCF neurons to acoustic stimuli consisted of a slow and a fast component. BMI mainly increased the slow component and an excitatory transmitter antagonist, d-2-amino-5-phosphonovalerate mainly suppressed the slow component. Therefore the response pattern of these thalamic neurons is shaped by both γ-aminobutyric acid-mediated inhibition and N-methyl-d-aspartate-mediated facilitation.
Nonstationary Noise Analysis of M Currents Simulated and Recorded in PC12 Cells
Authors: Villarroel Alvaro
Published: December 2017

Villarroel, Alvaro. Nonstationary noise analysis of M currents simulated and recorded in PC12 cells. J. Neurophysiol. 77: 2131–2138, 1997. M current relaxations recorded in PC12 cells were subjected to nonstationary noise analysis (NSNA) to obtain estimates of single-channel current ( i), channel number ( N), and open probability ( Po) for the channels responsible for M current. The analysis was constrained such that N and single-channel conductance were the same at two potentials. The relation between variance and current indicated that the fraction of channels open was 0.58 ± 0.06 (mean ± SD) and 0.05 ± 0.04 (mean ± SD; n = 9) at −33 and −63 mV, respectively. The single M channel conductance was 4.0 pS, and a density of 1 functional M channel per 4 μm2was estimated. Monte Carlo simulations of a two-state model of M channels were used to obtain sets of simulated macroscopic M currents that were subjected to the same NSNA procedure so as to evaluate the accuracy of M channel parameters obtained with this method. The influence of current rundown and filter frequency on estimates of i, N, and Powere evaluated. The single-channel parameters estimated from the simulations differed by <10% from actual values at any level of current rundown, N, or Po. The dispersion in the estimation of N and Poincreased as Podecreased. Decreasing filter frequency caused an underestimation of i, paralleled by an overestimation of N. The estimation of Powas relatively immune to the filter frequency, especially for data simulated with Po= 0.77.
Lateralization and Behavioral Correlation of Changes in Regional Cerebral Blood Flow With Classical Conditioning of the Human Eyeblink Response
Authors: Schreurs Bernard G. , Mcintosh Anthony R. , Bahro Marcel , Herscovitch Peter , Sunderland Trey , Molchan Susan E.
Published: December 2017

Schreurs, Bernard G., Anthony R. McIntosh, Marcel Bahro, Peter Herscovitch, Trey Sunderland, and Susan E. Molchan. Lateralization and behavioral correlation of changes in regional cerebral blood flow with classical conditioning of the human eyeblink response. J. Neurophysiol. 77: 2153–2163, 1997. Laterality of changes in regional cerebral blood flow (rCBF) during classical conditioning of the human eyeblink response was studied and changes in rCBF were correlated with conditioned responses. In 10 normal volunteers, rCBF was mapped with positron emission tomography and H215O during pairings of a binaural tone conditioned stimulus and an air puff unconditioned stimulus to the left eye. Control conditions consisted of explicitly unpaired presentations of the tone and air puff before (control) and after (extinction) pairings. During pairings, rCBF increased significantly in right primary auditory cortex (contralateral to air puff) and decreased significantly in left and right cerebellar cortex. There were also increases in rCBF in right auditory association cortex and left temporoccipital cortex. Decreases in rCBF were noted bilaterally in the temporal poles and in the left prefrontal cortex. Positive correlations between changes in rCBF and percent conditioned responses were located in middle cerebellum, right superior temporal cortex, left dorsal premotor cortex, right middle cingulate, and right superior temporal cortex. There were negative correlations in left inferior prefrontal cortex, left middle prefrontal cortex, and right inferior parietal cortex. The data replicate our previous findings of lateralized changes in rCBF following presentations of a binaural tone and air puff to the right eye and indicate that there are pairing-specific changes in primary auditory cortex and cerebellum that are not unique to the left or right hemisphere but are a function of the side of training. The commonalities as well as differences in regional involvement in our present and previous experiment as well as in other eyeblink studies illustrate the advantage of functional neuroimaging to quantify different strategies used by the brain to perform seemingly similar functions. Indeed, the data support the notion that learning-related changes can be detected in a number of specific, but not necessarily invariant, brain regions, and that the involvement of any one region is dependent on the characteristics of the particular learning situation.
Multiple Nonprimary Motor Areas in the Human Cortex
Authors: Fink Gereon R. , Frackowiak Richard S. J. , Pietrzyk Uwe , Passingham Richard E.
Published: December 2017

Fink, Gereon R., Richard S. J. Frackowiak, Uwe Pietrzyk, and Richard E. Passingham. Multiple nonprimary motor areas in the human cortex. J. Neurophysiol. 77: 2164–2174, 1997. We measured the distribution of regional cerebral blood flow with positron emission tomography while three subjects moved their hand, shoulder, or leg. The images were coregistered with each individual's anatomic magnetic resonance scans. The data were analyzed for each individual to avoid intersubject averaging and so to preserve individual gyral anatomy. Instead of inspecting all pixels, we prospectively restricted the data analysis to particular areas of interest. These were defined on basis of the anatomic and physiological literature on nonhuman primates. By examining only a subset of areas, we strengthened the power of the statistical analysis and thereby increased the confidence in reporting single subject data. On the lateral convexity, motor related activity was found for all three subjects in the primary motor cortex, lateral premotor cortex, and an opercular area within the premotor cortex. In addition, there was activation of somatosensory cortex (SI), the supplementary somatosensory area (SII) in the Sylvian fissure, and parietal association areas (Brodmann areas 5 and 40). There was also activation in the insula. We suggest that the activation in the dorsal premotor cortex may correspond with dorsal premotor area (PMd) as described in the macaque brain. We propose three hypotheses as to the probable location of vental premotor area (PMv) in the human brain. On the medial surface, motor-related activity was found for all three subjects in the leg areas of the primary motor cortex and somatosensory cortex and also activity for the hand, shoulder, and leg in the supplementary motor area (SMA) on the dorsal medial convexity and in three areas in the cingulate sulcus. We suggest that the three cingulate areas may correspond with rostral cingulate premotor area, dorsal cingulate motor area (CMAd), and ventral cingulate motor area (CMAv) as identified in the macaque brain. Somatotopic mapping was demonstrated in the primary motor and primary somatosensory cortex. In all three subjects, the arm region lay anterior to the leg region in parietal area 5. Also in all three subjects, the arm region lay anterior to the leg region in the supplementary motor cortex.
Rapid Development of Synaptic Connections and Plasticity Between Sensory Neurons and Motor Neurons ofAplysiain Cell Culture: Implications for Learning and Regulation of Synaptic Strength
Authors: Coulson Rosalind L. , Klein Marc
Published: December 2017

Coulson, Rosalind L. and Marc Klein. Rapid development of synaptic connections and plasticity between sensory neurons and motor neurons of Aplysia in cell culture: implications for learning and regulation of synaptic strength. J. Neurophysiol. 77: 2316–2327, 1997. We describe here the time course of functional synapse formation and of the development of short-term synaptic plasticity at Aplysia sensorimotor synapses in cell culture, as well as the effects of blocking protein synthesis or postsynaptic receptors on the development of synaptic transmission and plasticity. We find that synaptic responses can be elicited in 50% of sensory neuron–motor neuron pairs by 1 h after cell contact and that short-term homosynaptic depression and synaptic augmentation and restoration by the endogenous facilitatory transmitter serotonin are present at the earliest stages of synapse formation. Neither block of protein synthesis with anisomycin nor block of two types of postsynaptic glutamate receptor has any effect on the development of synaptic transmission or synaptic plasticity. The rapidity of synapse formation and maturation and their independence of protein synthesis suggest that changes in the number of functional synapses could contribute to short- and intermediate-term forms of synaptic plasticity and learning.
Enhancement of Whole Cell Synaptic Currents by Low Osmolarity and by Low [NaCl] in Rat Hippocampal Slices
Authors: Huang Rong , Bossut Daniel F. , Somjen George G.
Published: December 2017

Huang, Rong, Daniel F. Bossut, and George G. Somjen. Enhancement of whole cell synaptic currents by low osmolarity and by low [NaCl] in rat hippocampal slices. J. Neurophysiol. 77: 2349–2359, 1997. We recorded whole cell currents of patch-clamped neurons in stratum pyramidale of CA1 region of rat hippocampal tissue slices. Synaptic currents were evoked by orthodromic stimulation while holding potential of the neuron was varied from hyperpolarized to depolarized levels. Extracellular osmolarity (πo) was lowered by superfusion with artificial cerebrospinal fluid in which NaCl concentration ([NaCl]) was reduced. The effect of low extracellular NaCl was tested in additional trials in which NaCl was substituted by isosmolar fructose. Both lowering of πo and isosmotic lowering of extracellular [NaCl] ([NaCl]o) caused reversible increase of excitatory postsynaptic currents. The effect of lowering πo was concentration dependent, and it was significantly stronger than the effect of equivalent isosmotic lowering of [NaCl]o. Inhibitory postsynaptic currents also increased in many but not in all cases. Lowering of πo caused a prolongation of the time constant of relaxation of the capacitive charging current induced by small hyperpolarizing voltage steps. A virtual input capacitance, calculated by dividing this time constant by the input resistance, increased during hypotonic exposure. Isosmotic lowering of [NaCl]o had no effect on time constant or input capacitance. Depolarizing voltage commands evoked spikelike inward currents presumably representing Na+-dependent action potentials generated outside the voltage-clamped region of the cell. These current spikes became smaller in low πo and in low [NaCl]o. Broader, voltage-dependent, presumably Ca2+-mediated inward currents became more prominent during hypotonic exposure. We conclude that lowering of [NaCl]o causes enhancement of excitatory synaptic transmission. Transmission may be facilitated by the uptake of Ca2+ into presynaptic terminals as well as into postsynaptic target neurons, induced by the low [NaCl]o. Lowering of πo enhances synaptic transmission more than does a corresponding isosmotic lowering of [NaCl]. The excess increase recorded from the cell soma in low πo may in part be due to changing electrotonic length caused by the swelling of dendrites.
Physiology, Pharmacology, and Topography of Cholinergic Neocortical Oscillations In Vitro
Authors: Lukatch Heath S. , Maciver M. Bruce
Published: December 2017

Lukatch, Heath S. and M. Bruce MacIver. Physiology, pharmacology, and topography of cholinergic neocortical oscillations in vitro. J. Neurophysiol. 77: 2427–2445, 1997. Rat neocortical brain slices generated rhythmic extracellular field [microelectroencephalogram (micro-EEG)] oscillations at theta frequencies (3–12 Hz) when exposed to pharmacological conditions that mimicked endogenous ascending cholinergic and GABAergic inputs. Use of the specific receptor agonist and antagonist carbachol and bicuculline revealed that simultaneous muscarinic receptor activation and γ-aminobutyric acid-A (GABAA)-mediated disinhibition werenecessary to elicit neocortical oscillations. Rhythmic activity was independent of GABAB receptor activation, but required intact glutamatergic transmission, evidenced by blockade or disruption of oscillations by 6-cyano-7-nitroquinoxaline-2,3-dione and (±)-2-amino-5-phosphonovaleric acid, respectively. Multisite mapping studies showed that oscillations were localized to areas 29d and 18b (Oc2MM) and parts of areas 18a and 17. Peak oscillation amplitudes occurred in layer 2/3, and phase reversals were observed in layers 1 and 5. Current source density analysis revealed large-amplitude current sinks and sources in layers 2/3 and 5, respectively. An initial shift in peak inward current density from layer 1 to layer 2/3 indicated that two processes underlie an initial depolarization followed by oscillatory activity. Laminar transections localized oscillation-generating circuitry to superficial cortical layers and sharp-spike-generating circuitry to deep cortical layers. Whole cell recordings identified three distinct cell types based on response properties during rhythmic micro-EEG activity: oscillation-on (theta-on) and -off (theta-off) neurons, and transiently depolarizing glial cells. Theta-on neurons displayed membrane potential oscillations that increased in amplitude with hyperpolarization (from −30 to −90 mV). This, taken together with a glutamate antagonist-induced depression of rhythmic micro-EEG activity, indicated that cholinergically driven neocortical oscillations require excitatory synaptic transmission. We conclude that under the appropriate pharmacological conditions, neocortical brain slices were capable of producing localized theta frequency oscillations. Experiments examining oscillation physiology, pharmacology, and topography demonstrated that neocortical brain slice oscillations share many similarities with the in vivo and in vitro theta EEG activity recorded in other brain regions.
Responses of Rat Spinal Dorsal Horn Neurons to Intracutaneous Microinjection of Histamine, Capsaicin, and Other Irritants
Authors: Carstens E.
Published: December 2017

Carstens, E. Responses of rat spinal dorsal horn neurons to intracutaneous microinjection of histamine, capsaicin, and other irritants. J. Neurophysiol. 77: 2499–2514, 1997. To investigate the spinal processing of cutaneous pruritic and algesic stimuli, single-unit recordings were made from wide-dynamic-range-type lumbar spinal dorsal horn neurons in pentobarbital-sodium-anesthetized rats. Neuronal responses were recorded to mechanical and noxious thermal stimuli, as well as to microinjection (1 μl) of histamine (0.01–10% = 9 × 10−1–9 × 10−4 M), capsaicin (0.1% = 3.3 × 10−3 M), or other algesic chemicals into skin within the receptive field via intracutaneously placed needles. Most (84%) of the 89 neurons responded to intracutaneous (ic) microinjection of histamine with a brief phasic discharge followed by an afterdischarge of variable (s to min) duration. Ten minutes after ic microinjection of histamine (but not NaCl), there was a significant increase in the mean area of the low-threshold (but not high-threshold) portion of unit mechanical receptive fields. However, responses to graded pressure stimuli were not significantly affected after histamine. Responses did not exhibit significant tachyphylaxis when histamine microinjections were repeated at 5- or 10-min intervals. Unit responses significantly increased in a dose-related manner to microinjection of histamine at concentrations ranging across 4 orders of magnitude. Within 30 s after ic microinjection of the H1 antagonist cetirizine, unit responses to ic histamine delivered at the same skin site were significantly attenuated. Unit responses to histamine, as well as to noxious thermal stimulation, were significantly reduced after systemic administration of morphine (3.5 mg/kg ip) in a naloxone-reversible manner. Application of a mechanical rub, scratch, or a noxious heat stimulus during the unit's ongoing response to ic histamine produced a brief and marked excitation, often followed by a period of reduced ongoing discharge. Unit responses to histamine were markedly suppressed by electrical stimulation in the midbrain periaqueductal gray. Most (79%) histamine-responsive units tested also responded to ic microinjection of capsaicin. After the initial microinjection of capsaicin, subsequent responses to histamine and capsaicin microinjections were significantly reduced. Units also responded to ic ethanol (capsaicin vehicle) in a dose-related manner, and showed tachyphylaxis to repeated ic ethanol at 80% but not at 8%. The mean response to 80% ethanol was significantly smaller than to 0.1% capsaicin. All units tested also responded to topical application of mustard oil (50%) and ic serotonin (30 μg). The results are discussed in terms of theories that attempt to reconcile psychophysical and clinical observations of pain and itch sensation.
Activation of Ca2+-Dependent Currents in Dorsal Root Ganglion Neurons by Metabotropic Glutamate Receptors and Cyclic ADP-Ribose Precursors
Authors: Crawford Jane H. , Wootton John F. , Seabrook Guy R. , Scott Roderick H.
Published: December 2017

Crawford, Jane H., John F. Wootton, Guy R. Seabrook, and Roderick H. Scott. Activation of Ca2+-dependent currents in dorsal root ganglion neurons by metabotropic glutamate receptors and cyclic ADP-ribose precursors. J. Neurophysiol. 77: 2573–2584, 1997. Cultured dorsal root ganglion neurons were voltage clamped at −90 mV to study the effects of intracellular application of nicotinamide adenine dinucleotide (βNAD+), intracellular flash photolysis of caged 3′,5′-cyclic guanosine monophosphate (cGMP), and metabotropic glutamate receptor activation. The activation of metabotropic glutamate receptors evoked inward Ca2+-dependent currents in most cells. This was mimicked both by intracellular flash photolysis of the caged axial isomer of cGMP [P-1-(2-nitrophenyl)ethyl cGMP] and intracellular application of βNAD+. Whole cell Ca2+-activated inward currents were used as a physiological index of raised intracellular Ca2+levels. Extracellular application of 10 μM glutamate evoked the activation of Ca2+-dependent inward currents, thus reflecting a rise in intracellular Ca2+levels. Similar inward currents were also activated after isolation of metabotropic glutamate receptor activation by application of 10 μM glutamate in the presence of 20 μM 6-cyano-7-nitroquinoxaline-2,3-dione and 20 μM dizocilpine maleate (MK 801), or by extracellular application of 10 μM trans-(1 S,3 R)-1-amino-1,3-cyclopentanedicarboxylic acid. Intracellular photorelease of cGMP, from its caged axial isomer, in the presence of βNAD+was also able to evoke similar Ca2+-dependent inward currents. Intracellular application of βNAD+alone produced a concentration-dependent effect on inward current activity. Responses to both metabotropic glutamate receptor activation and cGMP were suppressed by intracellular ryanodine, chelation of intracellular Ca2+by bis-( o-aminophenoxy)- N,N,N′,N′-tetraacetic acid, and depletion of intracellular Ca2+stores, but were insensitive to the removal of extracellular Ca2+. Therefore both cGMP, possibly via a mechanism that involves βNAD+and/or cyclic ADP-ribose, and glutamate can mobilize intracellular Ca2+from ryanodine-sensitive stores in sensory neurons.
Development of Chewing in Children From 12 to 48 Months: Longitudinal Study of EMG Patterns
Authors: Green Jordan R. , Moore Christopher A. , Ruark Jacki L. , Rodda Paula R. , Morvée WENDY T. , Vanwitzenburg Marcus J.
Published: December 2017

Green, Jordan R., Christopher A. Moore, Jacki L. Ruark, Paula R. Rodda, Wendy T. Morvée, and Marcus J. VanWitzenburg. Development of chewing in children from 12 to 48 months: longitudinal study of EMG patterns. J. Neurophysiol. 77: 2704–2716, 1997. Developmental changes in the coordinative organization of masticatory muscles were examined longitudinally in four children over 49 experimental sessions spanning the age range of 12–48 mo. Electromyographic (EMG) records were obtained for right and left masseter muscles, right and left temporalis muscles, and the anterior belly of the digastric. Two independent analytic processes were employed, one that relied on identification of onset and offset of muscle activation and a second that used pairwise cross-correlational techniques. The results of these two analyses, which were found to be consistent with each other, demonstrated that the basic chewing pattern of reciprocally activated antagonistic muscle groups is established by 12 mo of age. Nevertheless, chewing efficiency appears to be improved through a variety of changes in the chewing pattern throughout early development. Coupling of activity among the jaw elevator muscles was shown to strengthen with maturation, and the synchrony of onset and offset of these muscles also increased. Coactivation of antagonistic muscles decreased significantly with development. This decrease in antagonistic coactivation and increase in synchrony among jaw elevators, and a parallel decrease in EMG burst duration, were taken as evidence of increased chewing efficiency. No significant differences in the frequency of chewing were found across the ages studied. Additional considerations include the appropriateness of this coordinative infrastructure for other developing oromotor skills, such as speech production. It is suggested that the relatively fixed coordinative framework for chewing exhibited by these children would not be suitable for adaptation to speech movements, which have been shown to rely on a much more variable and adjustable coordinative organization.
Effects of Anions on ATP-Activated Nonselective Cation Current in NG108-15 Cells
Authors: Kaiho Hiromi , Kimura Junko , Matsuoka Isao , Nakanishi Hironori
Published: December 2017

Kaiho, Hiromi, Junko Kimura, Isao Matsuoka, and Hironori Nakanishi. Effects of anions on ATP-activated nonselective cation current in NG108-15 cells. J. Neurophysiol. 77: 2717–2722, 1997. Extracellular ATP induces a nonselective cation current and elevates intracellular Ca2+concentration via P2Zreceptors in NG108-15 cells. We found that the ATP-induced nonselective cation current became larger in methanesulfonic acid (MS−) than in Cl−external solution. We therefore examined the effects of various external anions on the ATP-induced cation current with the use of the whole cell patch-clamp technique. The concentration-response curves for ATP were obtained in different anionic external solutions. The maximum current density ( Imax) and the concentration of agonist that gives 50% of maximum response (EC50) value of ATP were obtained by fitting the curves with the use of the Hill coefficient of 2. The apparent Imaxdecreased in the order of aspartic acid (Asp−) > MS−> F−> Cl−> Br−≥ I−. The apparent EC50values for ATP were shifted to the right in the sequence of Asp−< F−< MS−< Br−< Cl−< I−. Thus both Imaxand EC50values were affected by anions, indicating that anions are mixed-type inhibitors of the ATP-induced current. The shift of the EC50values of ATP indicates that anions interfere with ATP binding to the receptor. External Cl−was a noncompetitive inhibitor with respect to external Na+, a major cation carrying the ATP-induced current. We conclude that extracellular anions inhibit the ATP-induced nonselective cation current at least partly by interfering with ATP binding to the P2Zreceptor, which is associated with the nonselective cation channels.
Blockade of GABAergic Inhibition Reveals Reordered Cortical Somatotopic Maps in Rats That Sustained Neonatal Forelimb Removal
Authors: Lane Richard D. , Killackey Herbert P. , Rhoades Robert W.
Published: December 2017

Lane, Richard D., Herbert P. Killackey, and Robert W. Rhoades. Blockade of GABAergic inhibition reveals reordered cortical somatotopic maps in rats that sustained neonatal forelimb removal. J. Neurophysiol. 77: 2723–2735, 1997. A previous study from this laboratory demonstrated that forelimb removal at birth results in invasion of the cuneate nucleus (CN) by sciatic nerve axons and the development of CN cells including thalamic projection neurons with receptive fields that include both the forelimb stump and the hindlimb. However, recordings from unit clusters in lamina IV of the primary somatosensory cortex (SI) of these animals revealed the presence of only a very few sites in the forelimb stump representation where responses to hindlimb stimulation could also be recorded. In the present study we tested the possibility that input from the hindlimb was suppressed in lamina IV of the cortical stump representation via GABAergic inhibitory mechanisms by mapping this cortical region, applying the γ-aminobutyric acid-A (GABAA) and GABAB receptor antagonists bicuculline and phaclofen (50 μM each), and then remapping the same sites. In six neonatally manipulated rats, 15 of 242 sites (6.2%) in the stump representation responded to hindlimb stimulation before GABA receptor blockade and 107 (44.2%) of the same sites responded to stimulation of the hindlimb during blockade ( P < 0.05). In six normal adult rats, 7 of 264 sites (2.7%) in the forelimb representation responded to hindlimb stimulation before the application of bicuculline and phaclofen. During GABA receptor blockage, 31 of these sites (11.7%) responded to such stimulation ( P < 0.02 vs. the untreated normal cortex and P < 0.01 vs. the neonatally manipulated rats treated with GABA blockers). To specifically test the role of GABAA versus GABAB receptors in the inhibition of hindlimb input to the SI stump representation in rats that sustained neonatal forelimb removal, either bicuculline or phaclofen alone was applied to SI in nine neonatally manipulated animals. In four rats treated with bicuculline, 12 of 184 sites (6.5%) in the stump representation responded to hindlimb stimulation before treatment and 61 of 184 sites (33.2%) responded to such stimulation during application ( P < 0.01). In animals ( n = 5) treated with phaclofen, 18 of 251 sites (7.2%) responded to hindlimb stimulation before treatment and 64 of these sites (25.5%) responded to such stimulation during application ( P < 0.05). There was no significant difference between the results obtained with bicuculline alone, phaclofen alone, or the two GABA blockers delivered together ( P > 0.05). These results indicate that hindlimb input to the portion of SI representing the forelimb stump is functionally suppressed in rats that have sustained neonatal forelimb removal and that GABAergic inhibition, mediated by both GABAA and GABAB receptors, is involved in this process.
Presynaptically Silent Synapses: Spontaneously Active Terminals Without Stimulus-Evoked Release Demonstrated in Cortical Autapses
Authors: Kimura Fumitaka , Otsu Yo , Tsumoto Tadaharu
Published: December 2017

Kimura, Fumitaka, Yo Otsu, and Tadaharu Tsumoto. Presynaptically silent synapses: spontaneously active terminals without stimulus-evoked release demonstrated in cortical autapses. J. Neurophysiol. 77: 2805–2815, 1997. This study addresses the question of whether synapses that are capable of releasing transmitters spontaneously can also release them in an excitation-dependent manner. For this purpose, whole cell patch recordings were performed for a total of 48 excitatory solitary neurons in a microisland culture to observe excitatory autaptic currents elicited by spontaneous transmitter release as well as by somatic excitation. A somatic Na+-spike, induced in response to a short voltage step, evoked excitatory postsynaptic currents (EPSCs) of various amplitudes through the autapses; in some cases, no response was noticeable. To make sure that the recorded autaptic spontaneous EPSCs (sEPSCs) under a voltage clamp resulted from independent release of transmitters and were not associated with action potentials, sEPSCS in the presence and absence of tetrodotoxin (TTX) were compared in six cells. In the presence of TTX the evoked EPSCs were completely eliminated, whereas the sEPSCs were still observed and the amplitude distribution histograms were statistically not different from those recorded in the absence of TTX. A quantitative analysis of the sEPSCs (presumably miniature EPSCs) showed that the amplitude of stimulus-evoked EPSCs did not correlate with either the frequency or median amplitudes of the sEPSCs or the age of the culture. To identify whether the absence of stimulus-evoked response was caused either by conduction failure of excitation along the axons or by impairment of the release machinery that links the terminal depolarization to vesicle exocytosis, we examined whether high K+and hypertonic solutions could facilitate the spontaneous release of transmitters. Although the hypertonic solution increased the spontaneous release in all cells tested ( n = 18), the high K+solution had a differential effect in increasing spontaneous release, i.e., the cells with larger evoked responses were more readily facilitated by the high K+solution. Because the high K+solution induced depolarization of presynaptic terminals, the present results indicated that the smaller evoked responses were due to the larger number of impaired or “silent” presynaptic terminals that were unable to link presynaptic depolarization to transmitter release. In summary, the present experiments provided evidence that at least some of the presynaptic terminals are silent in response to stimuli, while remaining spontaneously active at the same time. Because this phenomenon is due to the lack of sensitivity to depolarization at the terminals, these synaptic terminals seem incapable of linking terminal depolarization to transmitter release.
Visualization of Calcium Influx Through Channels That Shape the Burst and Tonic Firing Modes of Thalamic Relay Cells
Authors: Zhou Qiang , Godwin Dwayne W. , O'Malley Donald M. , Adams Paul R.
Published: December 2017

Zhou, Qiang, Dwayne W. Godwin, Donald M. O'Malley, and Paul R. Adams. Visualization of calcium influx through channels that shape the burst and tonic firing modes of thalamic relay cells. J. Neurophysiol. 77: 2816–2825, 1997. Thalamic neurons have two firing modes: “tonic” and “burst.” During burst mode, both low-threshold (LT) and high-threshold (HT) calcium channels are activated, while in tonic mode, only the HT-type of calcium channel is activated. The calcium signals associated with each firing mode were investigated in rat thalamic slices using whole cell patch clamping and confocal calcium imaging. Action potentials were induced by direct current injection into thalamic relay cells loaded with a fluorescent calcium indicator. In both tonic and burst firing modes, large calcium signals were recorded throughout the soma and proximal dendrites. To map the distribution of the channels mediating these calcium fluxes, LT and HT currents were independently activated using specific voltage-clamp protocols. We focused on the proximal region of the cell (up to 50 μm from the soma) because it appeared to be well clamped. For a voltage pulse of a given size, the largest calcium signals were observed in the proximal dendrites with smaller signals occurring in the soma and nucleus. This was true for both LT and HT signals. Rapid imaging, using one-dimensional linescans, was used to more precisely localize the calcium influx. For both LT and HT channels, calcium influx occurred simultaneously throughout all imaged regions including the soma and proximal dendrites. The presence of sizable calcium signals in the dendrites, soma, and nucleus during both firing modes, and the presence of LT calcium channels in the proximal dendrite where sensory afferents synapse, have implications for both the electrical functioning of relay cells and the transmission of sensory information to cortex.
Animal Model Explains the Origins of the Cranial Dystonia Benign Essential Blepharospasm
Authors: Schicatano Edward J. , Basso Michele A. , Evinger Craig
Published: December 2017

Schicatano, Edward J., Michele A. Basso, and Craig Evinger. Animal model explains the origins of the cranial dystonia benign essential blepharospasm. J. Neurophysiol. 77: 2842–2846, 1997. The current study demonstrates that combining two mild alterations to the rat trigeminal reflex blink system reproduces the symptoms of benign essential blepharospasm, a cranial dystonia characterized by uncontrollable spasms of blinking. The first modification, a small striatal dopamine depletion, reduces the tonic inhibition of trigeminal reflex blink circuits. The second alteration, a slight weakening of the lid-closing orbicularis oculi muscle, begins an adaptive increase in the drive on trigeminal sensory-motor blink circuits that initiates blepharospasm. By themselves, neither of these modifications causes spasms of lid closure, but combined, they induce bilateral forceful blinking and spasms of lid closure. A two-factor model based on these rodent experiments may explain the development of benign essential blepharospasm in humans. The first factor, a subclinical loss of striatal dopamine, creates a permissive environment within the trigeminal blink circuits. The second factor, an external ophthalmic insult, precipitates benign essential blepharospasm. This two-factor model may also be applicable to the genesis of other cranial dystonias.
Urine-Derived Compound Evokes Membrane Responses in Mouse Vomeronasal Receptor Neurons
Authors: Moss Robert L. , Flynn Robert E. , Shen Xin-Ming , Dudley Carol , Shi Jiming , Novotny Milos
Published: December 2017

Moss, Robert L., Robert E. Flynn, Xin-Ming Shen, Carol Dudley, Jiming Shi, and Milos Novotny. Urine-derived compound evokes membrane responses in mouse vomeronasal receptor neurons. J. Neurophysiol. 77: 2856–2862, 1997. Sensory neurons of the vomeronasal organ (VNO) are thought to detect species-specific chemical signals important for reproductive function. The electrical properties of VNO neurons have begun to be characterized in a variety of species; however, the response of VNO neurons to possible physiological ligands has not yet been reported. One physiological effector, dehydro-exo-brevicomin (DHB), is found in the urine of intact male mice and affects the estrous cycle of female mice. In the present study, dissociated VNO neurons were voltage- or current-clamped and their response to DHB was determined. Approximately 26% of VNO neurons responded to DHB with an outward current at negative holding potentials; the current reversed at approximately +4 mV. Application of DHB in current-clamp mode produced membrane hyperpolarization and/or a reduction in the firing of action potentials. Because membrane conductance was shown to be decreased during application of DHB, the results suggest that the outward current associated with DHB application is a reflection of a reduction in inward current caused by closing an ion channel. This study provides the first evidence that a compound found in male urine directly affects VNO neurons.
Multiple Effects of Serotonin on Membrane Properties of Trigeminal Motoneurons In Vitro
Authors: Hsiao C. F. , Trueblood P. R. , Levine M. S. , Chandler S. H.
Published: December 2017

Hsiao, C. F., P. R. Trueblood, M. S. Levine, and S. H. Chandler. Multiple effects of serotonin on membrane properties of trigeminal motoneurons in vitro. J. Neurophysiol. 77: 2910–2924, 1997. Intracellular recordings from guinea pig trigeminal motoneurons (TMNs) in brain stem slices were used to determine the underlying ionic mechanisms responsible for our previously demonstrated enhancement of TMN excitability during jaw movements by serotonin (5-HT). 5-HT (0.5–100 μM) depolarized motoneurons and increased input resistance in the majority of neurons tested. Additionally, 5-HT reduced the amplitude of the postspike medium-duration afterhyperpolarization, decreased the current threshold for maintained spike discharge, and increased the maximum slope of the steady-state spike frequency-current relationship. Under voltage clamp, from holding potentials close to resting potential, 5-HT produced an inward current and a decrease in instantaneous slope conductance, suggesting a reduction in a resting K+ leak conductance ( I leak). The instantaneous current-voltage ( I-V) relationship for the inward 5-HT current ( I 5-HT) was linear throughout most of the voltage range tested. However, the steady-state I-V relationship showed some degree of inward rectification at potentials starting around −70 mV. The mean reversal potential for the instantaneous I 5-HT was −86.2 ± 4.5 (SE) mV ( n = 9), a value slightly negative to the predicted potassium equilibrium potential of −82 mV in these neurons. In the presence of 2 mM Ba2+, 5-HT application did not produce a further reduction in input conductance, but did expose a Ba2+-insensitive residual inward current that was resistant to Cs+ application. The instantaneous I-V relationship during 5-HT application in the presence of Ba2+ was shifted downward and parallel to control, suggesting that Ba2+ and 5-HT block the same resting I leak. The residual Ba2+- and Cs+-insensitive component of the total inward I 5-HT was voltage independent and was blocked when the extracellular Na+ was replaced by choline, suggesting that the predominant charge carrier for this residual current is Na+. 5-HT enhanced a hyperpolarization-activated cationic current, I h. In the presence of Ba2+, the time course of I 5-HT resembled that of I h and showed a similar voltage dependence that was blocked by extracellular Cs+ (1–3 mM). The effects of 5-HT on membrane potential, input resistance, and I h were partially mimicked by 5-HT2 agonists and suppressed by 5-HT2 antagonists. It is concluded that 5-HT enhances TMN membrane excitability through modulation of multiple intrinsic membrane conductances. This provides for a mechanism(s) to fine tune the input-output discharge properties of these neurons, thus providing them with greater flexibility in output in response to time-varying synaptic inputs during various movements of the jaw.