bluuebunny/crossref_metadata_2025 huggingface dataset:
Diameter-defined Strahler system and connectivity matrix of the pulmonary arterial tree
Authors: Jiang Z. L. , Kassab G. S. , Fung Y. C.
Published: December 2017

For modeling of a vascular tree for hemodynamic analysis, the well-known Weibel, Horsfield, and Strahler systems have three shortcomings: vessels of the same order are all treated as in parallel, despite the fact that some are connected in series; histograms of the diameters of vessels in the successive orders have wide overlaps; and the “small-twigs-on-large-trunks” phenomenon is not given a quantitative expression. To improve the accuracy of the hemodynamic circuit model, we made a distinction between vessel segments and vessel elements: a segment is a vessel between two successive nodes of bifurcation; an element is a union of a group of segments of the same order that are connected in series. In an equivalent circuit, all elements of the same order are considered as arranged in parallel. Then, we follow the ordering method of Horsfield and Strahler, with introduction of an additional rule for the assignment of order numbers. If Dn and SDn denote the mean and standard deviation of the diameters of vessels of order n, then our rule divides the gap between Dn--SDn and Dn--1 + SDn--1 evenly between orders n and n--1. Finally, we introduced a connectivity matrix with a component in the mth row and the nth column that is the average number of vessels of order m that grow out of the vessels of order n. This method was applied to the rat. We found that the rat pulmonary arterial tree has 11 orders of vessels and that the geometry is fractal within these orders. The ratios of diameters, lengths, and numbers of elements in successive orders are 1.58, 1.60, and 2.76, respectively. The connectivity matrix reveals interesting features beyond the fractal concept. New features are found in the variation of the total cross-sectional area of elements with order numbers.
Octopus Cells of the Mammalian Ventral Cochlear Nucleus Sense the Rate of Depolarization
Authors: Ferragamo Michael J. , Oertel Donata
Published: December 2017

Whole cell patch recordings in slices show that the probability of firing of action potentials in octopus cells of the ventral cochlear nucleus depends on the dynamic properties of depolarization. Octopus cells fired only when the rate of rise of a depolarization exceeded a threshold value that varied between 5 and 15 mV/ms among cells. The threshold rate of rise was independent of whether depolarizations were evoked synaptically or by the intracellular injection of current. Previous work showed that octopus cells are contacted by many auditory nerve fibers, each providing less than 1-mV depolarization. Summation of synaptic input from multiple fibers is required for an octopus cell to reach threshold. In firing only when synaptic depolarization exceeds a threshold rate, octopus cells fire selectively when synaptic input is sufficiently large and synchronized for the small, brief unitary excitatory postsynaptic potentials (EPSPs) to sum to produce a rapidly rising depolarization. The sensitivity to rate of depolarization is governed by a low-threshold, α-dendrotoxin-sensitive potassium conductance ( g KL). This conductance also shapes the peaks of action potentials, contributing to the precision in their timing. Firing in neighboring T stellate cells depends much less strongly on the rate of rise. They lack strong α-dendrotoxin-sensitive conductances. Octopus cells appear to be specialized to detect synchronization in the activation of groups of auditory nerve fibers, a common pattern in responses to natural sounds, and convey its occurrence with temporal precision.
Impaired Reaching and Grasping After Focal Inactivation of Globus Pallidus Pars Interna in the Monkey
Authors: Wenger Kristin K. , Musch Krystina L. , Mink Jonathan W.
Published: December 2017

The purpose of this study was to test the hypothesis that the basal ganglia output from globus pallidus pars interna (GPi) contributes to inhibition of competing motor patterns to prevent them from interfering with a volitional movement. To test this hypothesis, the kinematics of a natural reach, grasp, and retrieval task were measured in the monkey before and after focal inactivation in GPi with the GABAAagonist muscimol. Two rhesus monkeys were trained to reach in a parasagittal plane to grasp a 1-cm cube of apple and retrieve it. Reflective markers were applied to the shoulder, elbow, wrist, and index finger. Movements were videotaped at 60 fields/s, digitized, and analyzed off-line. In each session the monkey performed 12–15 reaches before and 12–15 reaches after injection of 0.5 μl of 8.8 mM muscimol. Muscimol was injected into 22 separate locations in the “arm” area of GPi. Inactivation of the GPi with muscimol produced movement deficits in a reach-grasp-retrieve task that can be summarized as follows: 1) decreased peak wrist velocity during the reach to target; 2) decreased elbow and shoulder angular velocities, with elbow angular velocity relatively more impaired than shoulder angular velocity; resulting in 3) higher maximum vertical wrist and index finger positions at the apex of the reach; 4) prolonged latency from the end of the reach to the completion of grasp; and 5) less impairment of retrieval than reach, with inactivation at the majority of sites causing no impairment and some actually speeding up retrieval despite slow reaching. The results of this study show that reaching movements are impaired in a specific way after focal inactivation of GPi in previously normal monkeys. The slowing of the reach with normal (or fast) retrieval suggests that there is difficulty inhibiting the posture holding mechanisms that were active before the reach, but that assist the retrieval. The nature of the impairment supports the hypothesis that GPi lesions disrupt the ability to inhibit competing motor mechanisms to prevent them from interfering with desired voluntary movement.
Hearing Impairment Induces Frequency-Specific Adjustments in Auditory Spatial Tuning in the Optic Tectum of Young Owls
Authors: Gold Joshua I. , Knudsen Eric I.
Published: December 2017

Bimodal, auditory-visual neurons in the optic tectum of the barn owl are sharply tuned for sound source location. The auditory receptive fields (RFs) of these neurons are restricted in space primarily as a consequence of their tuning for interaural time differences and interaural level differences across broad ranges of frequencies. In this study, we examined the extent to which frequency-specific features of early auditory experience shape the auditory spatial tuning of these neurons. We manipulated auditory experience by implanting in one ear canal an acoustic filtering device that altered the timing and level of sound reaching the eardrum in a frequency-dependent fashion. We assessed the auditory spatial tuning at individual tectal sites in normal owls and in owls raised with the filtering device. At each site, we measured a family of auditory RFs using broadband sound and narrowband sounds with different center frequencies both with and without the device in place. In normal owls, the narrowband RFs for a given site all included a common region of space that corresponded with the broadband RF and aligned with the site's visual RF. Acute insertion of the filtering device in normal owls shifted the locations of the narrowband RFs away from the visual RF, the magnitude and direction of the shifts depending on the frequency of the stimulus. In contrast, in owls that were raised wearing the device, narrowband and broadband RFs were aligned with visual RFs so long as the device was in the ear but not after it was removed, indicating that auditory spatial tuning had been adaptively altered by experience with the device. The frequency tuning of tectal neurons in device-reared owls was also altered from normal. The results demonstrate that experience during development adaptively modifies the representation of auditory space in the barn owl's optic tectum in a frequency-dependent manner.
Direct Visualization of Organ of Corti Kinematics in a Hemicochlea
Authors: Hu Xintian , Evans Burt N. , Dallos Peter
Published: December 2017

The basilar membrane in the mammalian cochlea vibrates when the cochlea receives a sound stimulus. This mechanical vibration is transduced into hair cell receptor potentials and thereafter encoded by action potentials in the auditory nerve. Knowledge of the mechanical transformation that converts basilar membrane vibration into hair cell stimulation has been limited, until recently, to hypothetical geometric models. Experimental observations are largely lacking to prove or disprove the validity of these models. We have developed a hemicochlea preparation to visualize the kinematics of the cochlear micromechanism. Direct mechanical drive of 1–2 Hz sinusoidal command was applied to the basilar membrane. Vibration patterns of the basilar membrane, inner and outer hair cells, supporting cells, and tectorial membrane have been recorded concurrently by means of a video optical flow technique. Basilar membrane vibration was driven in a direction transversal to its plane. However, the direction of the resulting vibration was found to be essentially radial at the level of the reticular lamina and cuticular plates of inner and outer hair cells. The tectorial membrane vibration was mainly transversal. The transmission ratio between cilia displacement of inner and outer hair cells and basilar membrane vibration is in the range of 0.7–1.1. These observations support, in part, the classical geometric models at low frequencies. However, there appears to be less tectorial membrane motion than predicted, and it is largely in the transversal direction.
Computational Analysis of Action Potential Initiation in Mitral Cell Soma and Dendrites Based on Dual Patch Recordings
Authors: Shen Gongyu Y. , Chen Wei R. , Midtgaard Jens , Shepherd Gordon M. , Hines Michael L.
Published: December 2017

In olfactory mitral cells, dual patch recordings show that the site of action potential initiation can shift between soma and distal primary dendrite and that the shift is dependent on the location and strength of electrode current injection. We have analyzed the mechanisms underlying this shift, using a model of the mitral cell that takes advantage of the constraints available from the two recording sites. Starting with homogeneous Hodgkin-Huxley-like Na+-K+ channel distribution in the soma-dendritic region and much higher sodium channel density in the axonal region, the model's channel kinetics and density were adjusted by a fitting algorithm so that the model response was virtually identical to the experimental data. The combination of loading effects and much higher sodium channel density in the axon relative to the soma-dendritic region results in significantly lower “voltage threshold” for action potential initiation in the axon; the axon therefore fires first unless the voltage gradient in the primary dendrite is steep enough for it to reach its higher threshold. The results thus provide a quantitative explanation for the stimulus strength and position dependence of the site of action potential initiation in the mitral cell.
GABAA Receptor–Mediated Miniature Postsynaptic Currents and α-Subunit Expression in Developing Cortical Neurons
Authors: Dunning D. D. , Hoover C. L. , Soltesz I. , Smith M. A. , O'Dowd D. K.
Published: December 2017

Previous studies have described maturational changes in GABAergic inhibitory synaptic transmission in the rodent somatosensory cortex during the early postnatal period. To determine whether alterations in the functional properties of synaptically localized GABAAreceptors (GABAARs) contribute to development of inhibitory transmission, we used the whole cell recording technique to examine GABAergic miniature postsynaptic currents (mPSCs) in developing cortical neurons. Neurons harvested from somatosensory cortices of newborn mice showed a progressive, eightfold increase in GABAergic mPSC frequency during the first 4 wk of development in dissociated cell culture. A twofold decrease in the decay time of the GABAergic mPSCs, between 1 and 4 wk, demonstrates a functional change in the properties of GABAARs mediating synaptic transmission in cortical neurons during development in culture. A similar maturational profile observed in GABAergic mPSC frequency and decay time in cortical neurons developing in vivo (assessed in slices), suggests that these changes in synaptically localized GABAARs contribute to development of inhibition in the rodent neocortex. Pharmacological and reverse transcription-polymerase chain reaction (RT-PCR) studies were conducted to determine whether changes in subunit expression might contribute to the observed developmental alterations in synaptic GABAARs. Zolpidem (300 nM), a subunit-selective benzodiazepine agonist with high affinity for α1-subunits, caused a reversible slowing of the mPSC decay kinetics in cultured cortical neurons. Development was characterized by an increase in the potency of zolpidem in modulating the mPSC decay, suggesting a maturational increase in percentage of functionally active GABAARs containing α1 subunits. The relative expression of α1 versus α5 GABAAR subunit mRNA in cortical tissue, both in vivo and in vitro, also increased during this same period. Furthermore, single-cell RT-multiplex PCR analysis revealed more rapidly decaying mPSCs in individual neurons in which α1 versus α5 mRNA was amplified. Together these data suggest that changes in α-subunit composition of GABAARs contribute to the maturation of GABAergic mPSCs mediating inhibition in developing cortical neurons.
Unilateral Dopamine Denervation Blocks Corticostriatal LTP
Authors: Centonze Diego , Gubellini Paolo , Picconi Barbara , Calabresi Paolo , Giacomini Patrizia , Bernardi Giorgio
Published: December 2017

The nigrostriatal dopaminergic projection is crucial for the striatal processing of motor information received from the cortex. Lesion of this pathway in rats causes locomotor alterations that resemble some of the symptoms of Parkinson's disease and significantly alters the excitatory transmission in the striatum. We performed in vitro electrophysiological recordings to study the effects of unilateral striatal dopamine (DA) denervation obtained by omolateral nigral injection of 6-hydroxydopamine (6-OHDA) in the formation of corticostriatal long-term potentiation (LTP). Unilateral nigral lesion did not affect the intrinsic membrane properties of striatal spiny neurons. In fact, these cells showed similar pattern of firing discharge and current-voltage relationship in denervated striata and in naive controlateral striata. Moreover, excitatory postsynaptic potentials (EPSPs) evoked by stimulating corticostriatal fibers and recorded from DA-denervated slices showed a pharmacology similar to that observed in slices obtained from controlateral intact striata. Conversely, in magnesium-free medium, high-frequency stimulation (HFS) of corticostriatal fibers produced LTP in slices from nondenervated striata but not in slices from 6-OHDA–denervated rats. After denervation, in fact, no significant changes in the amplitude of extra- and intracellular synaptic potentials were recorded after the conditioning HFS. The absence of corticostriatal LTP in DA-denervated striata might represent the cellular substrate for some of the movement disorders observed in Parkinson's disease.
Odor Specificity of Habituation in the Rat Anterior Piriform Cortex
Authors: Wilson Donald A.
Published: December 2017

Exposure to odorants results in a rapid (<10 s) reduction in odor-evoked activity in the rat piriform cortex despite relatively maintained afferent input from olfactory bulb mitral cells. To further understand this form of cortical plasticity, a detailed analysis of its odor specificity was performed. Habituation of odor responses in anterior piriform cortex single units was examined in anesthetized, freely breathing rats. The magnitude of single-unit responses of layer II/III neurons to 2-s odor pulses were examined before and after a 50-s habituating stimulus of either the same or different odor. The results demonstrated that odor habituation was odor specific, with no significant cross-habituation between either markedly different single odors or between odors within a series of straight chain alkanes. Furthermore, habituation to binary 1:1 mixtures produced minimal cross-habituation to the components of that mixture. These latter results may suggest synthetic odor processing in the olfactory system, with novel odor mixtures processed as unique stimuli. Potential mechanisms of odor habituation in the piriform cortex must be able to account for the high degree of specificity of this effect.
Neurophysiological Aspects of Eye and Eyelid Movements During Blinking in Humans
Authors: Bour L. J. , Aramideh M. , Ongerboer De Visser B. W.
Published: December 2017

The neural relationships between eyelid movements and eye movements during spontaneous, voluntary, and reflex blinking in a group of healthy subjects were examined. Electromyographic (EMG) recording of the orbicularis oculi (OO) muscles was performed using surface electrodes. Concurrently, horizontal and vertical eye positions were recorded by means of the double magnetic induction (DMI) ring method. In addition, movement of the upper eyelid was measured by a specially designed search coil, placed on the upper eyelid. The reflex blink was elicited electrically by supraorbital nerve stimulation either on the right or the left side. It is found that disconjugate oblique eye movements accompany spontaneous, voluntary as well as reflex blinking. Depending on the gaze position before blinking, the amplitude of horizontal and vertical components of the eye movement during blinking varies in a systematic way. With adduction and downward gaze the amplitude is minimal. With abduction the horizontal amplitude increases, whereas with upward gaze the vertical amplitude increases. Unilateral electrical supraorbital nerve stimulation at low currents elicits eye movements with a bilateral late component. At stimulus intensities approximately two to three times above the threshold, the early ipsilateral blink reflex response (R1) in the OO muscle can be observed together with an early ipsilateral eye movement component at a latency of ∼15 ms. In addition, during the electrical blink reflex, early ipsilateral and late bilateral components can also be identified in the upper eyelid movement. In contrast to the late bilateral component of upper eyelid movement, the early ipsilateral component of upper eyelid movement appears to open the eye to a greater degree. This early ipsilateral component of upper eyelid movement occurs more or less simultaneously with the early eye movement component. It is suggested that both early ipsilateral movements following electrical stimulation do not have a central neural origin. Late components of the eye movements slightly precede the late components of the eyelid movement. Synchrony between late components of eyelid movements and eye movements as well as similarity of oblique eye movement components in different types of blinking suggest the existence of a premotor neural structure acting as a generator that coordinates impulses to different subnuclei of the oculomotor nucleus as well as the facial nerve nucleus during blinking independent from the ocular saccadic and/or vergence system. The profile and direction of the eye movement rotation during blinking gives support to the idea that it may be secondary to eyeball retraction; an extra cocontraction of the inferior and superior rectus muscle would be sufficient to explain both eye retraction and rotation in the horizontal vertical and torsional planes.
Regional Differences in Hypoxic Depolarization and Swelling in Hippocampal Slices
Authors: Kreisman Norman R. , Soliman Soheil , Gozal David
Published: December 2017

Pyramidal neurons in the CA1 region of the hippocampus are highly vulnerable to damage from hypoxia-ischemia, whereas neurons in the CA3 region and the dentate gyrus are more resistant. A similar pattern of vulnerability to loss of synaptic and membrane function occurs in the in vitro hippocampal slice preparation, suggesting that intrinsic factors are important in acute neuronal damage. Simultaneous recordings of DC potential and imaging of changes in light transmittance were made in slices from the middle one-third of the hippocampus to characterize the initiation and spread of depolarization and swelling during hypoxia-aglycemia. Hypoxic depolarization (HD) and associated optical changes were initiated simultaneously in the stratum oriens of the CA1 region and thereafter spread to the stratum radiatum of CA1 and later to the upper (inner) blade of the dentate gyrus. A decrease in light transmittance was associated consistently with depolarization in all regions ( n = 22 slices). Investigation of the sequence of activation in intact slices showed that activation of the dentate gyrus arose independently of activation of the CA1 region. This was confirmed by recordings made from minislices in which CA1, CA3, and dentate regions were physically separated. HD and optical changes were never observed in the CA3 region, despite exposure to 40–60 min of combined hypoxia and aglycemia. In contrast, exposure to hypoxia after pretreatment of slices with altered tonicity or ion composition, which triggered episodes of spreading depolarization (SD), provoked depolarization and optical changes simultaneously in both CA1 and CA3 regions. Similarly, pretreatment with agents that cause severe metabolic impairment, such as dinitrophenol (DNP), also rendered the CA3 region vulnerable to subsequent hypoxia. This suggests that the CA3 region in hippocampal slices is normally resistant to HD and only becomes vulnerable after severe impairment of metabolic capacity. The similar order of vulnerability of in vitro and in vivo hippocampus to hypoxia-aglycemia supports the use of the hippocampal slice preparation to investigate early changes potentially contributing to hypoxic-ischemic injury.
Low-Voltage-Activated Calcium Current Does Not Regulate the Firing Behavior in Paired Mechanosensory Neurons With Different Adaptation Properties
Authors: Sekizawa Shin-Ichi , French Andrew S. , Torkkeli Päivi H.
Published: December 2017

Low-voltage-activated Ca2+ currents (LVA- I Ca) are believed to perform several roles in neurons such as lowering the threshold for action potentials, promoting burst firing and oscillatory behavior, and enhancing synaptic excitation. They also may allow rapid increases in intracellular Ca2+ concentration. We discovered LVA- I Ca in both members of paired mechanoreceptor neurons in a spider, where one neuron adapts rapidly (Type A) and the other slowly (Type B) in response to a step stimulus. To learn if I Ca contributed to the difference in adaptation behavior, we studied the kinetics of I Ca from isolated somata under single-electrode voltage-clamp and tested its physiological function under current clamp. LVA- I Ca was large enough to fire single action potentials when all other voltage-activated currents were blocked, but we found no evidence that it regulated firing behavior. LVA- I Ca did not lower the action potential threshold or affect firing frequency. Previous experiments have failed to find Ca2+-activated K+ current ( I K(Ca)) in the somata of these neurons, so it is also unlikely that LVA- I Ca interacts with I K(Ca) to produce oscillatory behavior. We conclude that LVA-Ca2+ channels in the somata, and possible in the dendrites, of these neurons open in response to the depolarization caused by receptor current and by the voltage-activated Na+ current ( I Na) that produces action potential(s). However, the role of the increased intracellular Ca2+ concentration in neuronal function remains enigmatic.
Prototypical Imidazoline-1 Receptor Ligand Moxonidine Activates Alpha2-Adrenoceptors in Bulbospinal Neurons of the RVL
Authors: Hayar Abdallah , Guyenet Patrice G.
Published: December 2017

Moxonidine is an antihypertensive drug that lowers sympathetic vasomotor tone by stimulating either alpha2-adrenergic (α2-AR) or imidazoline I1 receptors within the rostral ventrolateral medulla (RVL). In this study, we investigated the effects of moxonidine (10 μM) on RVL neurons in brain stem slices of neonatal rats. We recorded mainly from retrogradely labeled RVL bulbospinal neurons (putative presympathetic neurons) except for some extracellular recordings. Prazosin was used to block alpha1-adrenoceptors. Moxonidine inhibited the extracellularly recorded discharges of all spontaneously active RVL neurons tested (bulbospinal and unidentified). This effect was reversed or blocked by the selective α2-AR antagonist SKF 86466 (10 μM). In contrast, the I1 imidazoline ligand AGN 192403 (10 μM) had no effect on the spontaneous activity. In whole cell recordings (holding potential −70 mV), moxonidine produced a small and variable outward current (mean 7 pA). This current was observed in both tyrosine hydroxylase–immunoreactive and other bulbospinal neurons and was blocked by SKF 86466. Excitatory postsynaptic currents (EPSCs) evoked by focal electrical stimulation were isolated by incubation with gabazine and strychnine, and inhibitory postsynaptic currents (IPSCs) were isolated with 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX). Moxonidine reduced the amplitude of the evoked EPSCs (EC50 = 1 μM; 53% inhibition at 10 μM) but not their decay time constant (5.6 ms). The effect of moxonidine on EPSCs persisted in barium (300 μM) and was reduced ∼80% by SKF 86466. Moxonidine also reduced the amplitude of evoked IPSCs by 63%. In conclusion, moxonidine inhibits putative RVL presympathetic neurons both presynaptically and postsynaptically. All observed effects in the present study are consistent with an α2-AR agonist activity of moxonidine.
Precision of the Pacemaker Nucleus in a Weakly Electric Fish: Network Versus Cellular Influences
Authors: Moortgat Katherine T. , Bullock Theodore H. , Sejnowski Terrence J.
Published: December 2017

We investigated the relative influence of cellular and network properties on the extreme spike timing precision observed in the medullary pacemaker nucleus (Pn) of the weakly electric fish Apteronotus leptorhynchus. Of all known biological rhythms, the electric organ discharge of this and related species is the most temporally precise, with a coefficient of variation (CV = standard deviation/mean period) of 2 × 10−4 and standard deviation (SD) of 0.12–1.0 μs. The timing of the electric organ discharge is commanded by neurons of the Pn, individual cells of which we show in an in vitro preparation to have only a slightly lesser degree of precision. Among the 100–150 Pn neurons, dye injection into a pacemaker cell resulted in dye coupling in one to five other pacemaker cells and one to three relay cells, consistent with previous results. Relay cell fills, however, showed profuse dendrites and contacts never seen before: relay cell dendrites dye-coupled to one to seven pacemaker and one to seven relay cells. Moderate (0.1–10 nA) intracellular current injection had no effect on a neuron's spiking period, and only slightly modulated its spike amplitude, but could reset the spike phase. In contrast, massive hyperpolarizing current injections (15–25 nA) could force the cell to skip spikes. The relative timing of subthreshold and full spikes suggested that at least some pacemaker cells are likely to be intrinsic oscillators. The relative amplitudes of the subthreshold and full spikes gave a lower bound to the gap junctional coupling coefficient of 0.01–0.08. Three drugs, called gap junction blockers for their mode of action in other preparations, caused immediate and substantial reduction in frequency, altered the phase lag between pairs of neurons, and later caused the spike amplitude to drop, without altering the spike timing precision. Thus we conclude that the high precision of the normal Pn rhythm does not require maximal gap junction conductances between neurons that have ordinary cellular precision. Rather, the spiking precision can be explained as an intrinsic cellular property while the gap junctions act to frequency- and phase-lock the network oscillations.
Gap Junction Effects on Precision and Frequency of a Model Pacemaker Network
Authors: Moortgat Katherine T. , Bullock Theodore H. , Sejnowski Terrence J.
Published: December 2017

We investigated the precision of spike timing in a model of gap junction-coupled oscillatory neurons. The model incorporated the known physiology, morphology, and connectivity of the weakly electric fish's high-frequency and extremely precise pacemaker nucleus (Pn). Two neuron classes, pacemaker and relay cells, were each modeled with two compartments containing Hodgkin-Huxley sodium and potassium currents. Isolated pacemaker cells fired periodically, due to a constant current injection; relay cells were silent but slightly depolarized at rest. When coupled by gap junctions to other neurons, a model neuron, like its biological correlate, spiked at frequencies and amplitudes that were largely independent of current injections. The phase distribution in the network was labile to intracellular current injections and to gap junction conductance changes. The model predicts a biologically plausible gap junction conductance of 4–5 nS (200–250 MΩ). This results in a coupling coefficient of ∼0.02, as observed in vitro. Network parameters were varied to test which could improve the temporal precision of oscillations. Increased gap junction conductances and larger numbers of cells (holding total junctional conductance per cell constant) both substantially reduced the coefficient of variation (CV = standard deviation/mean) of relay cell spike times by 74–85% and more, and did so with lower gap junction conductance when cells were contacted axonically compared with somatically. Pacemaker cell CV was only reduced when the probability of contact was increased, and then only moderately: a fivefold increase in the probability of contact reduced CV by 35%. We conclude that gap junctions facilitate synchronization, can reduce CV, are most effective between axons, and that pacemaker cells must have low intrinsic CV to account for the low CV of cells in the biological network.
CA3-Released Entorhinal Seizures Disclose Dentate Gyrus Epileptogenicity and Unmask a Temporoammonic Pathway
Authors: Barbarosie Michaela , Louvel Jacques , Kurcewicz Irène , Avoli Massimo
Published: December 2017

We have investigated the propagation of epileptiform discharges induced by 4-aminopyridine (4-AP, 50 μM) in adult mouse hippocampus-entorhinal cortex slices, before and after Schaffer collateral cut. 4-AP application induced 1) ictal epileptiform activity that disappeared over time and 2) interictal epileptiform discharges, which continued throughout the experiment. Using simultaneous field potential and [K+]orecordings, we found that entorhinal and dentate ictal epileptiform discharges were accompanied by comparable elevations in [K+]o (up to 12 mM from a baseline value of 3.2 mM), whereas smaller rises in [K+]o (up to 6 mM) were associated with ictal activity in CA3. Cutting the Schaffer collaterals disclosed the occurrence of ictal discharges that were associated with larger rises in [K+]o as compared with the intact slice. Further lesion of the perforant path blocked ictal activity and the associated [K+]o increases in the dentate gyrus, indicating synaptic propagation to this area. Time delay measurements demonstrated that ictal epileptiform activity in the intact hippocampal-entorhinal cortex slice propagated via the trisynaptic path. However, after Schaffer collateral cut, ictal discharges continued to occur in CA1 and subiculum and spread to these areas directly from the entorhinal cortex. Thus our data indicate that the increased epileptogenicity of the dentate gyrus (a prominent feature of temporal lobe epilepsy as well), may depend on perforant path propagation of entorhinal ictal discharges, irrespective of mossy fiber reorganization. Moreover, hippocampal neuronal damage that is acutely mimicked in our model by Schaffer collateral cut, may contribute to “short-circuit” propagation of activity by pathways that are masked when the hippocampus is intact.
Group I, II, and III mGluR Compounds Affect Rhythm Generation in the Gastric Circuit of the Crustacean Stomatogastric Ganglion
Authors: Krenz Wulf D. , Nguyen Don , Pérez-Acevedo Nivia L. , Selverston Allen I.
Published: December 2017

We have studied the effects of group I, II, and III metabotropic glutamate receptor (mGluR) agonists on rhythm generation by the gastric circuit of the stomatogastric ganglion (STG) of the Caribbean spiny lobster Panulirus argus. All mGluR agonists and some antagonists we tested in this study had clear and distinct effects on gastric rhythm generation when superfused over combined oscillating or blocked silent STG preparations. A consistent difference between group I agonists and group II and III agonists was that group I agonists acted excitatory. The group I-specific agonists l-quisqualic acid and ( S)-3,5-dihydroxyphenylglycine, as well as the nonspecific agonist (1S,3R)-1-aminocyclopentane-1,3-dicarboxylic acid accelerated ongoing rhythms and could induce gastric rhythms in silent preparations. The group II agonist (2S,1′S,2′S)-2-(carboxycyclopropyl)glycine (L-CCG-I) and the group III agonist l(+)-2-amino-4-phosphonobutyric acid (l-AP4) slowed down or completely blocked ongoing gastric rhythms and were without detectable effect on silent preparations. The action of L-CCG-I was blocked partially by the group-II-specific antagonist, (RS)-1-amino-5-phosphonoindan-1-carboxylic acid [(RS)APICA], and the group-III-specific antagonist (RS)-α-methyl-4-phosphonophenylglycine completely blocked the action of l-AP4. Besides its antagonistic action, the group-II-specific antagonist (RS)APICA had a remarkably strong apparent inverse agonist action when applied alone on oscillating preparations. The action of all drugs was dose dependent and reversible, although recovery was not always complete. In our experiments, the effects of none of the mGluR-specific agonists were antagonized or amplified by the N-methyl-d-aspartate (NMDA)-receptor-specific antagonistd(−)-2-amino-5-phosphonopentanoic acid, excluding the contamination of responses to mGluR agonists by nonspecific cross-reactivity with NMDA receptors. Picrotoxin did not prevent the inhibitory action of L-CCG-I and l-AP4. We conclude that mGluRs, probably similar to those belonging to groups I, II, and III described in mammals, may play a role as modulators of gastric circuit rhythm generation in vivo.
Neuromuscular System of the Flexible Arm of the Octopus: Physiological Characterization
Authors: Matzner Henry , Gutfreund Yoram , Hochner Binyamin
Published: December 2017

The octopus arm is an outstanding example of an efficient boneless and highly flexible appendage. We have begun characterizing the neuromuscular system of the octopus arm in both innervated muscle preparations and dissociated muscle cells. Functionally antagonistic longitudinal and transverse muscle fibers showed no differences in membrane properties and mode of innervation. The muscle cells are excitable but have a broad range of linear membrane properties. They are electrotonically very compact so that localized synaptic inputs can control the membrane potential of the entire muscle cell. Three distinct excitatory neuronal inputs to each arm muscle cell were identified; their reversal potentials were extrapolated to be about −10 mV. These appear to be cholinergic as they are blocked by hexamethonium, d-tubocurarine, and atropine. Two inputs have low quantal amplitude (1–7 mV) and slow rise times (4–15 ms), whereas the third has a large size (5–25 mV) and fast rise time (2–4 ms). This large synaptic input is most likely due to exceptionally large quantal events. The probability of release is rather low, suggesting a stochastic activation of muscle cells. All inputs demonstrated a modest activity-dependent plasticity typical of fast neuromuscular systems. The pre- and postsynaptic properties suggest a rather direct relation between neuronal activity and muscle action. The lack of significant electrical coupling between muscle fibers and the indications for the small size of the motor units suggest that the neuromuscular system of the octopus arm has evolved to ensure a high level of precise localization in the neural control of arm function.
Inactivation of Parietal and Prefrontal Cortex Reveals Interdependence of Neural Activity During Memory-Guided Saccades
Authors: Chafee Matthew V. , Goldman-Rakic Patricia S.
Published: December 2017

Dorsolateral prefrontal and posterior parietal cortex share reciprocal projections. They also share nearly identical patterns of neuronal activation during performance of memory-guided saccades. To test the hypothesis that the reciprocal projections between parietal and prefrontal neurons may entrain their parallel activation, the present experiments have combined cortical cooling in one cortical area with single-unit recording in the other to more precisely determine the physiological interactions between the two during working memory performance. The activity of 105 cortical neurons during the performance of an oculomotor delayed response (ODR) task (43 parietal neurons during prefrontal cooling, 62 prefrontal neurons during parietal cooling) was compared across two blocks of trials collected while the distant cortical area either was maintained at normal body temperature or cooled. The mean firing rates of 71% of the prefrontal neurons during ODR performance changed significantly when parietal cortex was cooled. Prefrontal neurons the activity of which was modulated during the cue, delay, or saccade periods of the task were equally vulnerable to parietal inactivation. Further, both lower and higher firing rates relative to the precool period were seen with comparable frequency. Similar results were obtained from the converse experiment, in which the mean firing rates of 76% of the parietal neurons were significantly different while prefrontal cortex was cooled, specifically in those task epochs when the activity of each neuron was modulated during ODR performance. These effects again were seen equally in all epochs of the ODR task in the form of augmented or suppressed activity. Significant effects on the latency of neuronal activation during cue and saccade periods of the task were absent irrespective of the area cooled. Cooling was associated in some cases with a shift in the best direction of Gaussian tuning functions fit to neuronal activity, and these shifts were on average larger during parietal than prefrontal cooling. In view of the parallel between the similarity in activity patterns previously reported and the largely symmetrical cooling effects presently obtained, the data suggest that prefrontal and parietal neurons achieve matched activation during ODR performance through a symmetrical exchange of neuronal signals between them; in both cortical areas, neurons activated during the cue, delay, and also saccade epochs of the ODR task participate in reciprocal neurotransmission; and the output of each cortical area produces a mixture of excitatory and inhibitory drives within its target.
Chronic NMDA Exposure Accelerates Development of GABAergic Inhibition in the Superior Colliculus
Authors: Aamodt Sandra M. , Shi Jian , Colonnese Matthew T. , Veras Wellington , Constantine-Paton Martha
Published: December 2017

Maturation of excitatory synaptic connections depends on the amount and pattern of their activity, and activity can affect development of inhibitory synapses as well. In the superficial visual layers of the superior colliculus (sSC), developmental increases in the effectiveness of γ-aminobutyric acid (GABAA) receptor–mediated inhibition may be driven by the maturation of visual inputs. In the rat sSC, GABAAreceptor currents significantly jump in amplitude between postnatal days 17 and 18( P17 and P18), approximately when the effects of cortical inputs are first detected in collicular neurons. We manipulated the development of these currents in vivo by implanting a drug-infused slice of the ethylene-vinyl acetate copolymer Elvax over the superior colliculus of P8 rats to chronically release from this plastic low levels of N-methyl-d-aspartate (NMDA). Sham-treated control animals received a similar implant containing only the solvent for NMDA. To examine the effects of this treatment on the development of GABA-mediated neurotransmission, we used whole cell voltage-clamp recording of spontaneous synaptic currents (sPSCs) from sSC neurons in untreated, NMDA-treated, and sham-treated superior colliculus slices ranging in age from 10 to 20 days postnatal. Both amplitude and frequency of sPSCs were studied at holding potentials of +50 mV in the presence and absence of the GABAAreceptor antagonist, bicuculline methiodide (BMI). The normal developmental increase in GABAAreceptor currents occurred on schedule ( P18) in sham-treated sSC, but NMDA treatment caused premature up-regulation ( P12). The average sPSCs in early NMDA-treated neurons were significantly larger than in age-matched sham controls or in age-matched, untreated neurons. No differences in average sPSC amplitudes across treatments or ages were present in BMI-insensitive, predominantly glutamatergic synaptic currents of the same neurons. NMDA treatment also significantly increased levels of glutamate decarboxylase (GAD), measured by quantitative western blotting with staining at P13 and P19. Cell counting using the dissector method for MAP 2 and GAD67at P13 and P19indicated that the differences in GABAergic transmission were not due to increases in the proportion of inhibitory to excitatory neurons after NMDA treatment. However, chronic treatments begun at P8 with Elvax containing both NMDA and BMI significantly decreased total neuron density at P19 (∼15%), suggesting that the NMDA-induced increase in GABAAreceptor currents may protect against excitotoxicity.
Primate Translational Vestibuloocular Reflexes. II. Version and Vergence Responses to Fore-Aft Motion
Authors: McHenry M. Quinn , Angelaki Dora E.
Published: December 2017

To maintain binocular fixation on near targets during fore-aft translational disturbances, largely disjunctive eye movements are elicited the amplitude and direction of which should be tuned to the horizontal and vertical eccentricities of the target. The eye movements generated during this task have been investigated here as trained rhesus monkeys fixated isovergence targets at different horizontal and vertical eccentricities during 10 Hz fore-aft oscillations. The elicited eye movements complied with the geometric requirements for binocular fixation, although not ideally. First, the corresponding vergence angle for which the movement of each eye would be compensatory was consistently less than that dictated by the actual fixation parameters. Second, the eye position with zero sensitivity to translation was not straight ahead, as geometrically required, but rather exhibited a systematic dependence on viewing distance and vergence angle. Third, responses were asymmetric, with gains being larger for abducting and downward compared with adducting and upward gaze directions, respectively. As frequency was varied between 4 and 12 Hz, responses exhibited high-pass filter properties with significant differences between abduction and adduction responses. As a result of these differences, vergence sensitivity increased as a function of frequency with a steeper slope than that of version. Despite largely undercompensatory version responses, vergence sensitivity was closer to ideal. Moreover, the observed dependence of vergence sensitivity on vergence angle, which was varied between 2.5 and 10 MA, was largely linear rather than quadratic (as geometrically predicted). We conclude that the spatial tuning of eye velocity sensitivity as a function of gaze and viewing distance follows the general geometric dependencies required for the maintenance of foveal visual acuity. However, systematic deviations from ideal behavior exist that might reflect asymmetric processing of abduction/adduction responses perhaps because of different functional dependencies of version and vergence eye movement components during translation.
Response Differences in Monkey TE and Perirhinal Cortex: Stimulus Association Related to Reward Schedules
Authors: Liu Zheng , Richmond Barry J.
Published: December 2017

Anatomic and behavioral evidence shows that TE and perirhinal cortices are two directly connected but distinct inferior temporal areas. Despite this distinctness, physiological properties of neurons in these two areas generally have been similar with neurons in both areas showing selectivity for complex visual patterns and showing response modulations related to behavioral context in the sequential delayed match-to-sample (DMS) trials, attention, and stimulus familiarity. Here we identify physiological differences in the neuronal activity of these two areas. We recorded single neurons from area TE and perirhinal cortex while the monkeys performed a simple behavioral task using randomly interleaved visually cued reward schedules of one, two, or three DMS trials. The monkeys used the cue's relation to the reward schedule (indicated by the brightness) to adjust their behavioral performance. They performed most quickly and most accurately in trials in which reward was immediately forthcoming and progressively less well as more intermediate trials remained. Thus the monkeys appeared more motivated as they progressed through the trial schedule. Neurons in both TE and perirhinal cortex responded to both the visual cues related to the reward schedules and the stimulus patterns used in the DMS trials. As expected, neurons in both areas showed response selectivity to the DMS patterns, and significant, but small, modulations related to the behavioral context in the DMS trial. However, TE and perirhinal neurons showed strikingly different response properties. The latency distribution of perirhinal responses was centered 66 ms later than the distribution of TE responses, a larger difference than the 10–15 ms usually found in sequentially connected visual cortical areas. In TE, cue-related responses were related to the cue's brightness. In perirhinal cortex, cue-related responses were related to the trial schedules independently of the cue's brightness. For example, some perirhinal neurons responded in the first trial of any reward schedule including the one trial schedule, whereas other neurons failed to respond in the first trial but respond in the last trial of any schedule. The majority of perirhinal neurons had more complicated relations to the schedule. The cue-related activity of TE neurons is interpreted most parsimoniously as a response to the stimulus brightness, whereas the cue-related activity of perirhinal neurons is interpreted most parsimoniously as carrying associative information about the animal's progress through the reward schedule. Perirhinal cortex may be part of a system gauging the relation between work schedules and rewards.