bluuebunny/crossref_metadata_2025 huggingface dataset:
Cortical Representation of the Sensory Dimension of Pain
Authors: Hofbauer Robert K. , Rainville Pierre , Duncan Gary H. , Bushnell M. Catherine
Published: December 2017

It is well accepted that pain is a multidimensional experience, but little is known of how the brain represents these dimensions. We used positron emission tomography (PET) to indirectly measure pain-evoked cerebral activity before and after hypnotic suggestions were given to modulate the perceived intensity of a painful stimulus. These techniques were similar to those of a previous study in which we gave suggestions to modulate the perceived unpleasantness of a noxious stimulus. Ten volunteers were scanned while tonic warm and noxious heat stimuli were presented to the hand during four experimental conditions: alert control, hypnosis control, hypnotic suggestions for increased-pain intensity and hypnotic suggestions for decreased-pain intensity. As shown in previous brain imaging studies, noxious thermal stimuli presented during the alert and hypnosis-control conditions reliably activated contralateral structures, including primary somatosensory cortex (S1), secondary somatosensory cortex (S2), anterior cingulate cortex, and insular cortex. Hypnotic modulation of the intensity of the pain sensation led to significant changes in pain-evoked activity within S1 in contrast to our previous study in which specific modulation of pain unpleasantness (affect), independent of pain intensity, produced specific changes within the ACC. This double dissociation of cortical modulation indicates a relative specialization of the sensory and the classical limbic cortical areas in the processing of the sensory and affective dimensions of pain.
Role of Inhibition in Cortical Reorganization of the Adult Raccoon Revealed by Microiontophoretic Blockade of GABAAReceptors
Authors: Tremere Liisa , Hicks T. Philip , Rasmusson Douglas D.
Published: December 2017

Cortical reorganization was induced by amputation of the 4th digit in 11 adult raccoons. Animals were studied at various intervals, ranging from 2 to 37 wk, after amputation. Recordings were made from a total of 129 neurons in the deafferented cortical region using multibarrel micropipettes. Several types of receptive fields were described in reorganized cortex: restricted fields were similar in size to the normal receptive fields in nonamputated animals; multi-regional fields included sensitive regions on both adjacent digits and/or the underlying palm and were either continuous over the entire field or consisted of split fields. The proportion of neurons with restricted fields increased with time after amputation and was greater than previously found in subcortical regions. A GABAAreceptor antagonist (bicuculline methiodide), glutamate, and GABA were administered iontophoretically to these neurons while determining their receptive fields and thresholds. Bicuculline administration resulted in expansion of the receptive field in 60% of the 93 neurons with cutaneous fields. In most cases (33 neurons) this consisted of a simple expansion around the borders of the predrug receptive field, and the average expansion (426%) was not different from that seen in nonamputated animals. In some neurons ( n = 4), bicuculline produced an expansion from one digit onto the adjacent palm or another digit, an effect never seen in control animals. Bicuculline also changed the split fields of seven neurons into continuous fields by exposing a responsive region between the split fields. Finally, bicuculline changed the internal receptive field organization of 10 neurons by revealing subfields with reduced thresholds. In contrast to the situation in nonamputated animals, iontophoretic administration of glutamate also produced receptive field expansion in some neurons ( n = 6), but the size and/or shape of the change was different from that produced by bicuculline, indicating that the effects of bicuculline were not due to an overall facilitation of neuronal activity. These results are consistent with the hypotheses that an important component of long-term cortical reorganization is the gradual reduction in effective receptive field size and that intracortical inhibitory networks are partially responsible for these changes.
Pathway-Specific Targeting of GABAAReceptor Subtypes to Somatic and Dendritic Synapses in the Central Amygdala
Authors: Delaney Andrew J. , Sah Pankaj
Published: December 2017

Neurons in the central amygdala express two distinct types of ionotropic GABA receptor. One is the classical GABAAreceptor that is blocked by low concentrations of bicuculline and positively modulated by benzodiazepines. The other is a novel type of ionotropic GABA receptor that is less sensitive to bicuculline but blocked by the GABACreceptor antagonist (1,2,5,6-tetrohydropyridine-4-yl) methylphosphinic acid (TPMPA) and by benzodiazepines. In this study, we examine the distribution of these two receptor types. Recordings of GABAergic miniature inhibitory postsynaptic currents (mIPSCs) showed a wide variation in amplitude. Most events had amplitudes of <50 pA, but a small minority had amplitudes >100 pA. Large-amplitude events also had rise times faster than small-amplitude events. Large-amplitude events were fully blocked by 10 μM bicuculline but unaffected by TPMPA. Small amplitude events were partially blocked by both bicuculline and TPMPA. Focal application of hypertonic sucrose to the soma evoked large-amplitude mIPSCs, whereas focal dendritic application of sucrose evoked small-amplitude mIPSCs. Thus inhibitory synapses on the dendrites of neurons in the central amygdala express both types of GABA receptor, but somatic synapses expressed purely GABAAreceptors. Minimal stimulation revealed that inhibitory inputs arising from the laterally located intercalated cells innervate dendritic synapses, whereas inhibitory inputs of medial origin innervated somatic inhibitory synapses. These results show that different types of ionotropic GABA receptors are targeted to spatially and functionally distinct synapses. Thus benzodiazepines will have different modulatory effects on different inhibitory pathways in the central amygdala.
Intracellular Correlates of Spatial Memory Acquisition in Hippocampal Slices: Long-Term Disinhibition of CA1 Pyramidal Cells
Authors: Gusev Pavel A. , Alkon Daniel L.
Published: December 2017

Despite many advances in our understanding of synaptic models of memory such as long-term potentiation and depression, cellular mechanisms that correlate with and may underlie behavioral learning and memory have not yet been conclusively determined. We used multiple intracellular recordings to study learning-specific modifications of intrinsic membrane and synaptic responses of the CA1 pyramidal cells (PCs) in slices of the rat dorsal hippocampus prepared at different stages of the Morris water maze (WM) task acquisition. Schaffer collateral stimulation evoked complex postsynaptic potentials (PSP) consisting of the excitatory and inhibitory postsynaptic potentials (EPSP and IPSP, respectively). After rats had learned the WM task, our major learning-specific findings included reduction of the mean peak amplitude of the IPSPs, delays in the mean peak latencies of the EPSPs and IPSPs, and correlation of the depolarizing-shifted IPSP reversal potentials and reduced IPSP-evoked membrane conductance. In addition, detailed isochronal analyses revealed that amplitudes of both early and late IPSP phases were reduced in a subset of the CA1 PCs after WM training was completed. These reduced IPSPs were significantly correlated with decreased IPSP conductance and with depolarizing-shifted IPSP reversal potentials. Input-output relations and initial rising slopes of the EPSP phase did not indicate learning-related facilitation as compared with the swim and naı̈ve controls. Another subset of WM-trained CA1 PCs had enhanced amplitudes of action potentials but no learning-specific synaptic changes. There were no WM training-specific modifications of other intrinsic membrane properties. These data suggest that long-term disinhibition in a subset of CA1 PCs may facilitate cell discharges that represent and record the spatial location of a hidden platform in a Morris WM.
Genetic Suppression of Seizure Susceptibility inDrosophila
Authors: Kuebler Daniel , Zhang Haiguang , Ren Xiaoyun , Tanouye Mark A.
Published: December 2017

Despite the frequency of seizure disorders in the human population, the genetic and physiological basis for these defects has been difficult to resolve. Although many genetic defects that cause seizure susceptibility have been identified, the defects involve disparate biological processes, many of which are not neural specific. The large number and heterogeneous nature of the genes involved makes it difficult to understand the complex factors underlying the etiology of seizure disorders. Examining the effect known genetic mutations have on seizure susceptibility is one approach that may prove fruitful. This approach may be helpful both in understanding how different physiological processes affect seizure susceptibility and in identifying novel therapeutic treatments. In this study, we have taken advantage of Drosophila, a genetically tractable system, to identify factors that suppress seizure susceptibility. Of particular interest has been a group of Drosophila mutants, the bang-sensitive (BS) mutants, which are much more susceptible to seizures than wild type. The BS phenotypic class includes at least eight genes, including three examined in this study, bss, eas, and sda. Through the generation of double-mutant combinations with other well-characterized Drosophilamutants, the BS mutants are particularly useful for identifying genetic factors that suppress susceptibility to seizures. We have found that mutants affecting Na+channels, mlenaptsand para, K+channels, Sh, and electrical synapses, shak-B2, can suppress seizures in the BS mutants. This is the first demonstration that these types of mutations can suppress the development of seizures in any organism. Reduced neuronal excitability may contribute to seizure suppression. The best suppressor, mlenapts, causes an increased stimulation threshold for the giant fiber (GF) consistent with a reduction in single neuron excitability that could underlie suppression of seizures. For some other double mutants with para and ShKS133, there are no GF threshold changes, but reduced excitability may also be indicated by a reduction in GF following frequency. These results demonstrate the utility of Drosophila as a model system for studying seizure susceptibility and identify physiological processes that modify seizure susceptibility.
Feature Analysis of Natural Sounds in the Songbird Auditory Forebrain
Authors: Sen Kamal , Theunissen Frédéric E. , Doupe Allison J.
Published: December 2017

Although understanding the processing of natural sounds is an important goal in auditory neuroscience, relatively little is known about the neural coding of these sounds. Recently we demonstrated that the spectral temporal receptive field (STRF), a description of the stimulus-response function of auditory neurons, could be derived from responses to arbitrary ensembles of complex sounds including vocalizations. In this study, we use this method to investigate the auditory processing of natural sounds in the birdsong system. We obtain neural responses from several regions of the songbird auditory forebrain to a large ensemble of bird songs and use these data to calculate the STRFs, which are the best linear model of the spectral-temporal features of sound to which auditory neurons respond. We find that these neurons respond to a wide variety of features in songs ranging from simple tonal components to more complex spectral-temporal structures such as frequency sweeps and multi-peaked frequency stacks. We quantify spectral and temporal characteristics of these features by extracting several parameters from the STRFs. Moreover, we assess the linearity versus nonlinearity of encoding by quantifying the quality of the predictions of the neural responses to songs obtained using the STRFs. Our results reveal successively complex functional stages of song analysis by neurons in the auditory forebrain. When we map the properties of auditory forebrain neurons, as characterized by the STRF parameters, onto conventional anatomical subdivisions of the auditory forebrain, we find that although some properties are shared across different subregions, the distribution of several parameters is suggestive of hierarchical processing.
Quantitative Response Characteristics of Thermoreceptive and Nociceptive Lamina I Spinothalamic Neurons in the Cat
Authors: Craig A. D. , Krout K. , Andrew D.
Published: December 2017

The physiological characteristics of antidromically identified lamina I spinothalamic (STT) neurons in the lumbosacral spinal cord were examined using quantitative thermal and mechanical stimuli in barbiturate-anesthetized cats. Cells belonging to the three main recognized classes were included based on categorization with natural cutaneous stimulation of the hindpaw: nociceptive-specific (NS), polymodal nociceptive (HPC), or thermoreceptive-specific (COOL) cells. The mean central conduction latencies of these classes differed significantly; NS = 130.8 ± 55.5 (SD) ms ( n= 100), HPC = 72.1 ± 28.0 ms ( n = 128), and COOL = 58.6 ± 25.3 ms ( n = 136), which correspond to conduction velocities of 2.5, 4.6, and 5.6 m/s. Based on recordings made prior to any noxious stimulation, the mean spontaneous discharge rates of these classes also differed: NS = 0.5 ± 0.7 imp/s ( n = 47), HPC = 0.9 ± 0.7 imp/s ( n = 59), and COOL = 3.3 ± 2.6 imp/s ( n = 107). Standard, quantitative, thermal stimulus sequences applied with a Peltier thermode were used to characterize the stimulus-response functions of 76 COOL cells, 47 HPC cells, and 37 NS cells. The COOL cells showed a very linear output from 34°C down to ∼15°C and a maintained plateau thereafter. The HPC cells showed a fairly linear but accelerating response to cold below a median threshold of ∼24°C and down to 9°C (measured at the skin-thermode interface with a thermode temperature of 2°C). The HPC cells and the NS cells both showed rapidly increasing, sigmoidal response functions to noxious heat with a fairly linear response between 45 and 53°C, but they had significantly different thresholds; half of the HPC cells were activated at ∼45.5°C and half of the NS cells at ∼43°C. The 20 HPC lamina I STT cells and 10 NS cells tested with quantitative pinch stimuli showed fairly linear responses above a threshold of ∼130 g/mm2 for HPC cells and a threshold of ∼100 g/mm2 for NS cells. All of these response functions compare well (across species) with the available data on the characteristics of thermoreceptive and nociceptive primary afferent fibers and the appropriate psychophysics in humans. Together these results support the concept that these classes of lamina I STT cells provide discrete sensory channels for the sensations of temperature and pain.
Horizontal Vestibuloocular Reflex Evoked by High-Acceleration Rotations in the Squirrel Monkey. IV. Responses After Spectacle-Induced Adaptation
Authors: Clendaniel Richard A. , Lasker David M. , Minor Lloyd B.
Published: December 2017

The horizontal angular vestibuloocular reflex (VOR) evoked by sinusoidal rotations from 0.5 to 15 Hz and acceleration steps up to 3,000°/s2 to 150°/s was studied in six squirrel monkeys following adaptation with ×2.2 magnifying and ×0.45 minimizing spectacles. For sinusoidal rotations with peak velocities of 20°/s, there were significant changes in gain at all frequencies; however, the greatest gain changes occurred at the lower frequencies. The frequency- and velocity-dependent gain enhancement seen in normal monkeys was accentuated following adaptation to magnifying spectacles and diminished with adaptation to minimizing spectacles. A differential increase in gain for the steps of acceleration was noted after adaptation to the magnifying spectacles. The gain during the acceleration portion, G A, of a step of acceleration (3,000°/s2 to 150°/s) increased from preadaptation values of 1.05 ± 0.08 to 1.96 ± 0.16, while the gain during the velocity plateau, G V, only increased from 0.93 ± 0.04 to 1.36 ± 0.08. Polynomial fits to the trajectory of the response during the acceleration step revealed a greater increase in the cubic than the linear term following adaptation with the magnifying lenses. Following adaptation to the minimizing lenses, the value of G A decreased to 0.61 ± 0.08, and the value of G V decreased to 0.59 ± 0.09 for the 3,000°/s2 steps of acceleration. Polynomial fits to the trajectory of the response during the acceleration step revealed that there was a significantly greater reduction in the cubic term than in the linear term following adaptation with the minimizing lenses. These findings indicate that there is greater modification of the nonlinear as compared with the linear component of the VOR with spectacle-induced adaptation. In addition, the latency to the onset of the adapted response varied with the dynamics of the stimulus. The findings were modeled with a bilateral model of the VOR containing linear and nonlinear pathways that describe the normal behavior and adaptive processes. Adaptation for the linear pathway is described by a transfer function that shows the dependence of adaptation on the frequency of the head movement. The adaptive process for the nonlinear pathway is a gain enhancement element that provides for the accentuated gain with rising head velocity and the increased cubic component of the responses to steps of acceleration. While this model is substantially different from earlier models of VOR adaptation, it accounts for the data in the present experiments and also predicts the findings observed in the earlier studies.
Dorsal Root Ganglion Neurons Express Multiple Nicotinic Acetylcholine Receptor Subtypes
Authors: Genzen Jonathan R. , Van Cleve William , McGehee Daniel S.
Published: December 2017

Although nicotinic agonists can modulate sensory transmission, particularly nociceptive signaling, remarkably little is known about the functional expression of nicotinic acetylcholine receptors (nAChRs) on primary sensory neurons. We have utilized molecular and electrophysiological techniques to characterize the functional diversity of nAChR expression on mammalian dorsal root ganglion (DRG) neurons. RT-PCR analysis of subunit mRNA in DRG tissue revealed the presence of nAChR subunits α2–7 and β2–β4. Using whole cell patch-clamp recording and rapid application of nicotinic agonists, four pharmacologically distinct categories of nicotinic responses were identified in cultured DRG neurons. Capacitance measurements were used to divide neurons into populations of large and small cells, and the prevalence of nicotinic responses was compared between groups. Category I (α7-like) responses were seen in 77% of large neurons and 32% of small neurons and were antagonized by 10 nM methyllycaconitine citrate (MLA) or or 50 nM α-bungarotoxin (α-BTX). Category II (α3β4-like) responses were seen in 16% of large neurons and 9% of small neurons and were antagonized by 20 μM mecamylamine but not 10 nM MLA or 1 μM DHβE. Category II responses had a higher sensitivity to cytisine than nicotine. Two other types of responses were identified in a much smaller percentage of neurons and were classified as either category III (α4β2-like) or category IV (subtype unknown) responses. Both the α7-like and α3β4-like responses could be desensitized by prolonged applications of the analgesic epibatidine.
Experimental Simulation of Cat Electromyogram: Evidence for Algebraic Summation of Motor-Unit Action-Potential Trains
Authors: Day Scott J. , Hulliger Manuel
Published: December 2017

Prompted by the observation that the slope of the relationship between average rectified electromyography (EMG) and the ensemble activation rate of a pool of motor units progressively decreased (showing a downward nonlinearity), an experimental study was carried out to test the widely held notion that the EMG is the simple algebraic sum of motor-unit action-potential trains. The experiments were performed on the cat soleus muscle under isometric conditions, using electrical stimulation of α-motor axons isolated in ventral root filaments. The EMG signals were simulated experimentally under conditions where the activation of nearly the entire pool of motor units or of subsets of motor units was completely controlled by the experimenter. Sets of individual motor units or of small groups of motor units were stimulated independently, using stimulation profiles that were strictly repeatable between trials. This permitted a rigorous quantitative comparison of EMGs that were recorded during combined activation of multiple motor filaments with EMGs that were synthesized from the algebraic summation of motor unit action potential trains generated by individual nerve filaments. These were recorded separately by individually stimulating the same filaments with the same activation profiles that were employed during combined stimulation. During combined activation of up to 10 motor filaments, experimentally recorded and computationally synthesized EMGs were virtually identical. This indicates that EMG signals indeed are the outcome of the simple algebraic summation of motor-unit action-potential trains generated by concurrently active motor units. For both recorded and synthesized EMGs, it was confirmed that EMG magnitude increased nonlinearly with the ensemble activation rate of a pool of motor units. The nonlinearity was largely abolished when EMG magnitude was estimated as the sum of rectified, instead of raw, motor-unit action-potential trains. This suggests that the downward nonlinearity in the EMG-ensemble activation rate relation is due to signal cancellation arising from the perfectly linear summation of positive and negative components of action-potential waveforms. The findings provide a much needed post hoc validation of the concept of EMG generation by strict algebraic summation of motor unit action potentials that is generally relied on in theoretical modeling studies of EMG and in EMG decomposition algorithms.
Activity-Dependent Nitric Oxide Concentration Dynamics in the Laterodorsal Tegmental Nucleus In Vitro
Authors: Leonard C. S. , Michaelis E. K. , Mitchell K. M.
Published: December 2017

The behavioral-state related firing of mesopontine cholinergic neurons of the laterodorsal tegmental nucleus appears pivotal for generating both arousal and rapid-eye-movement sleep. Since these neurons express high levels of nitric oxide synthase, we investigated whether their firing increases local extracellular nitric oxide levels. We measured nitric oxide in the laterodorsal tegmental nucleus with a selective electrochemical microprobe (35 μm diam) in brain slices. Local electrical stimulation at 10 or 100 Hz produced electrochemical responses that were attributable to nitric oxide. Stimulus trains (100 Hz; 1 s) produced biphasic increases in nitric oxide that reached a mean peak concentration of 33 ± 2 (SE) nM at 4.8 ± 0.4 s after train onset and decayed to a plateau concentration of 8 ± 1 nM that lasted an average of 157 ± 23.4 s ( n= 14). These responses were inhibited by N G-nitro-l-arginine-methyl-ester (1 mM; 92% reduction of peak; n = 3) and depended on extracellular Ca2+. Chemically reduced hemoglobin attenuated both the electrically evoked responses and those produced by authentic nitric oxide. Application of the precursor,l-arginine (5 mM) augmented the duration of the electrically evoked response, while tetrodotoxin (1 μM) abolished it. Analysis of the stimulus-evoked field potentials indicated that electrically evoked nitric oxide production resulted from a direct, rather than synaptic, activation of laterodorsal tegmental neurons because neither nitric oxide production nor the field potentials were blocked by ionotropic glutamate receptor inhibitors. Nevertheless, application of N-methyl-d-aspartate also increased local nitric oxide concentration by 39 ± 14 nM ( n = 8). Collectively, these data demonstrate that laterodorsal tegmental neuron activity elevates extracellular nitric oxide concentration probably via somatodendritic nitric oxide production. These data support the hypothesis that nitric oxide can function as a local paracrine signal during the states of arousal and rapid-eye-movement sleep when the firing of mesopontine cholinergic neurons are highest.
Rapid Translocation of Zn2+From Presynaptic Terminals Into Postsynaptic Hippocampal Neurons After Physiological Stimulation
Authors: Li Yang , Hough Christopher J. , Suh Sang Won , Sarvey John M. , Frederickson Christopher J.
Published: December 2017

Zn2+is found in glutamatergic nerve terminals throughout the mammalian forebrain and has diverse extracellular and intracellular actions. The anatomical location and possible synaptic signaling role for this cation have led to the hypothesis that Zn2+is released from presynaptic boutons, traverses the synaptic cleft, and enters postsynaptic neurons. However, these events have not been directly observed or characterized. Here we show, using microfluorescence imaging in rat hippocampal slices, that brief trains of electrical stimulation of mossy fibers caused immediate release of Zn2+from synaptic terminals into the extracellular microenvironment. Release was induced across a broad range of stimulus intensities and frequencies, including those likely to induce long-term potentiation. The amount of Zn2+release was dependent on stimulation frequency (1–200 Hz) and intensity. Release of Zn2+required sodium-dependent action potentials and was dependent on extracellular Ca2+. Once released, Zn2+crosses the synaptic cleft and enters postsynaptic neurons, producing increases in intracellular Zn2+concentration. These results indicate that, like a neurotransmitter, Zn2+is stored in synaptic vesicles and is released into the synaptic cleft. However, unlike conventional transmitters, it also enters postsynaptic neurons, where it may have manifold physiological functions as an intracellular second messenger.
Dynamic Dissociation of Visual Selection From Saccade Programming in Frontal Eye Field
Authors: Murthy Aditya , Thompson Kirk G. , Schall Jeffrey D.
Published: December 2017

Previous studies of visually responsive neurons in the frontal eye fields have identified a selection process preceding saccades during visual search. The goal of this experiment was to determine whether the selection process corresponds to the selection of a conspicuous stimulus or to preparation of the next saccade. This was accomplished with the use of a novel task, called search-step, in which the target of a singleton visual search array switches location with a distracter on random trials. The target step trials created a condition in which the same stimulus yielded saccades either toward or away from the target. Visually responsive neurons in frontal eye field selected the current location of the conspicuous target even when gaze shifted to the location of a distractor. This dissociation demonstrates that the selection process manifest in visual neurons in the frontal eye field may be an explicit interpretation of the image and not an obligatory saccade command.
Electrophysiological and Morphological Changes in Striatal Spiny Neurons in R6/2 Huntington's Disease Transgenic Mice
Authors: Klapstein Gloria J. , Fisher Robin S. , Zanjani Hadi , Cepeda Carlos , Jokel Eve S. , Chesselet Marie-Françoise , Levine Michael S.
Published: December 2017

We examined passive and active membrane properties and synaptic responses of medium-sized spiny striatal neurons in brain slices from presymptomatic (∼40 days of age) and symptomatic (∼90 days of age) R6/2 transgenics, a mouse model of Huntington's disease (HD) and their age-matched wild-type (WT) controls. This transgenic expresses exon 1 of the human HD gene with ∼150 CAG repeats and displays a progressive behavioral phenotype associated with numerous neuronal alterations. Intracellular recordings were obtained using standard techniques from R6/2 and age-matched WT mice. Few electrophysiological changes occurred in striatal neurons from presymptomatic R6/2 mice. The changes in this age group were increased neuronal input resistance and lower stimulus intensity to evoke action potentials (rheobase). Symptomatic R6/2 mice exhibited numerous electrophysiological alterations, including depolarized resting membrane potentials, increased input resistances, decreased membrane time constants, and alterations in action potentials. Increased stimulus intensities were required to evoke excitatory postsynaptic potentials (EPSPs) in neurons from symptomatic R6/2 transgenics. These EPSPs had slower rise times and did not decay back to baseline by 45 ms, suggesting a more prominent component mediated by activation of N-methyl-d-aspartate receptors. Neurons from both pre- and symptomatic R6/2 mice exhibited reduced paired-pulse facilitation. Data from biocytin-filled or Golgi-impregnated neurons demonstrated decreased dendritic spine densities, smaller diameters of dendritic shafts, and smaller dendritic fields in symptomatic R6/2 mice. Taken together, these findings indicate that passive and active membrane and synaptic properties of medium-sized spiny neurons are altered in the R6/2 transgenic. These physiological and morphological alterations will affect communication in the basal ganglia circuitry. Furthermore, they suggest areas to target for pharmacotherapies to alleviate and reduce the symptoms of HD.
Control of Finger Grip Forces in Overarm Throws Made by Skilled Throwers
Authors: Hore J. , Watts S. , Leschuk M. , MacDougall A.
Published: December 2017

In an overarm throw, as the hand opens and the ball rolls along the fingers, the ball exerts a back force on the fingers. Previous studies suggested that skilled throwers compensate for this back force by producing an appropriate finger flexor torque to oppose the back force, but it was unclear how this is controlled by the CNS. We investigated whether the increase in finger flexor torque is timed precisely to occur late in the throw as the fingers open or whether the increase occurs throughout the throw to anticipate the increase in hand acceleration. Recreational ball players threw balls of different weights and diameters at different speeds from both a sitting and standing position while arm joint rotations were recorded with the search-coil technique. Force transducers were taped to the distal and middle phalanges of the middle finger and subjects released the ball from this finger. Passive forces on the finger were also recorded in “fake” throws in which the ball was taped to the finger and subjects did not grip the ball. These skilled throwers correctly anticipated the magnitude of the back force from the ball on the finger because the mean amplitude of finger extension did not increase in throws made with a large range of increasing back forces. This was achieved by subjects gripping the ball during the backswing with a force proportional to ball weight and intended ball speed (acceleration) and progressively increasing the grip force throughout the backswing and forward throw. The magnitude of this grip force during the forward throw was not affected by ball texture. After ball release from the fingertip, the finger flexed in proportion to the peak force on the finger before ball release. It is concluded, in a skilled fast overarm throw where large, fast-changing forces on the fingers result from the sum of motions at all arm joints, that finger flexor torque is progressively increased throughout the throw in an anticipatory (predictive) fashion to counteract the progressively increasing back force from the ball.
Increased Variability in Finger Position Occurs Throughout Overarm Throws Made by Cerebellar and Unskilled Subjects
Authors: Timmann D. , Citron R. , Watts S. , Hore J.
Published: December 2017

We investigated the ability of cerebellar patients and unskilled subjects to control finger grip position and the amplitude of finger opening during a multijoint overarm throw. This situation is of interest because the appropriate finger control requires predicting the magnitude of back forces from the ball on the finger throughout the throw and generating the appropriate level and rate of change of finger flexor torque to oppose the back force. Cerebellar patients, matched controls, and unskilled subjects threw tennis balls and tennis-sized balls of different weights. In all cases angular positions of five arm segments in three dimension were recorded at 1,000 Hz with the search-coil technique as subjects threw from a seated position. When the hand was stationary, cerebellar patients showed a normal ability to grip the ball and open the fingers and drop the ball. In contrast, in overarm throws where a back force occurred on the fingers, cerebellar patients showed an abnormally large variability in amplitude of the change in finger position when gripping, in amplitude of finger opening, and in amplitude of the change in finger position 10 ms after ball release. This was not due to more trial-to-trial variation in throwing speed. When throwing balls of increasing weights, both controls and cerebellar patients had increasing finger flexions after ball release that indicated that, on average, both scaled finger force in proportion to ball weight during the throw. Unlike skilled controls, cerebellar patients showed a small (<20°) increase in the amplitude of finger opening with balls of increasing weight. However, neither the increase in variability of finger position nor the increase in finger amplitude with balls of increasing weight were unique cerebellar signs because both were observed to various degrees in unskilled throwers. It is concluded that in the absence of either normal cerebellar function or skill, the central neural activity that controls finger opening in throwing can increase finger flexor force to oppose an increase in back force from heavier balls and can open the fingers but cannot control finger force or finger opening precisely and consistently from throw to throw. These results fit with the idea that cerebellar disorders are greater in multijoint than single-joint movements because control of force is more complicated. They are also consistent with the hypothesis that the cerebellum produces skill in movement by reducing variability in the timing and force of muscle contractions.
Integration of Perspective and Disparity Cues in Surface-Orientation–Selective Neurons of Area CIP
Authors: Tsutsui Ken-Ichiro , Jiang Min , Yara Kazuo , Sakata Hideo , Taira Masato
Published: December 2017

We investigated the effects of linear perspective and binocular disparity, as monocular and binocular depth cues, respectively, on the response of surface-orientation–selective (SOS) neurons in the caudal part of the lateral bank of the intraparietal sulcus (area CIP). During the single-unit recording, monkeys were required to perform the delayed-matching-to-sample (successive same/different discrimination) of discriminating surface orientation in stereoscopic computer graphics. Of 211 visually responsive neurons, 66 were intensively tested using the solid-figure stereogram (SFS) of a square plate with both disparity and perspective cues (D+P condition), and 62 of these were identified as SOS neurons for responding selectively to the orientation of stimuli. All these neurons were further tested using a solid figure with perspective cues alone (P-only condition), and 58% (36/62) of these showed selective response to the orientation of the stimuli. Of the 62 SOS neurons, 35 neurons were also tested using SFS with disparity cues alone (D-only condition) in addition to the D+P and P-only conditions. We classified these 35 neurons into four groups by comparing the response selectivity under the P-only and D-only conditions. More than one-half of these (19/35) were sensitive to both perspective and disparity cues (DP neurons), and nearly one-third (11/35) of these were sensitive to disparity cues alone (D neurons), but a few (2/35) were sensitive to perspective cues alone (P neurons). The remaining (3/35) neurons exhibited orientation selectivity only when both cues were present. In DP neurons, the preferred orientation under the D+P condition was correlated to those under the D-only and P-only conditions, and the response magnitude under the D+P condition was greater than those under the D-only and P-only conditions, suggesting the integration of both cues for the perception of surface orientation. However, in these neurons, the orientation tuning sharpness under the D+P and D-only conditions was higher than that under the P-only condition, suggesting the dominance of disparity cues. After the single-unit recording experiments, muscimol was microinjected into the recording site to temporarily inactivate its function. In all three effective cases out of six microinjection experiments, discrimination of a three-dimensional (3D) surface orientation was impaired when disparity cues alone were present. In only one effective case, when a relatively large amount of muscimol was microinjected, discrimination of a 3D surface orientation was impaired even when both disparity and perspective cues were present. These results suggest that linear perspective is an important cue for representations of a 3D surface of SOS neurons in area CIP, although it is less effective than binocular disparity, and that both of these depth cues may be integrated in area CIP for the perception of surface orientation in depth.
Dichotomy of Action-Potential Backpropagation in CA1 Pyramidal Neuron Dendrites
Authors: Golding Nace L. , Kath William L. , Spruston Nelson
Published: December 2017

In hippocampal CA1 pyramidal neurons, action potentials are typically initiated in the axon and backpropagate into the dendrites, shaping the integration of synaptic activity and influencing the induction of synaptic plasticity. Despite previous reports describing action-potential propagation in the proximal apical dendrites, the extent to which action potentials invade the distal dendrites of CA1 pyramidal neurons remains controversial. Using paired somatic and dendritic whole cell recordings, we find that in the dendrites proximal to 280 μm from the soma, single backpropagating action potentials exhibit <50% attenuation from their amplitude in the soma. However, in dendritic recordings distal to 300 μm from the soma, action potentials in most cells backpropagated either strongly (26–42% attenuation; n = 9/20) or weakly (71–87% attenuation; n = 10/20) with only one cell exhibiting an intermediate value (45% attenuation). In experiments combining dual somatic and dendritic whole cell recordings with calcium imaging, the amount of calcium influx triggered by backpropagating action potentials was correlated with the extent of action-potential invasion of the distal dendrites. Quantitative morphometric analyses revealed that the dichotomy in action-potential backpropagation occurred in the presence of only subtle differences in either the diameter of the primary apical dendrite or branching pattern. In addition, action-potential backpropagation was not dependent on a number of electrophysiological parameters (input resistance, resting potential, voltage sensitivity of dendritic spike amplitude). There was, however, a striking correlation of the shape of the action potential at the soma with its amplitude in the dendrite; larger, faster-rising, and narrower somatic action potentials exhibited more attenuation in the distal dendrites (300–410 μm from the soma). Simple compartmental models of CA1 pyramidal neurons revealed that a dichotomy in action-potential backpropagation could be generated in response to subtle manipulations of the distribution of either sodium or potassium channels in the dendrites. Backpropagation efficacy could also be influenced by local alterations in dendritic side branches, but these effects were highly sensitive to model parameters. Based on these findings, we hypothesize that the observed dichotomy in dendritic action-potential amplitude is conferred primarily by differences in the distribution, density, or modulatory state of voltage-gated channels along the somatodendritic axis.
Overlap of Saccadic and Pursuit Eye Movement Systems in the Brain Stem Reticular Formation
Authors: Yan Yi-Jun , Cui Dong-Mei , Lynch James C.
Published: December 2017

Recent physiological studies have suggested that there are several sites of interaction between the neural pathways that control saccadic eye movements and those that control visual pursuit movements. To address the question of saccade/pursuit interaction from a neuroanatomical point of view, we have studied the connections from the smooth and saccadic eye movement subregions of the frontal eye field (FEFsem and FEFsac, respectively) to the rostral interstitial nucleus of the medial longitudinal fasciculus (riMLF) in four Cebus apella monkeys. The riMLF has traditionally been considered to be a premotor center for vertical saccadic eye movements on the basis of single neuron recording experiments, microstimulation experiments, and surgical or chemical lesion experiments. We localized the functional subregions of the FEF with the use of low-threshold (≤50 μA) intracortical microstimulation. Biotinylated dextran amine or lectin from triticum vulgaris (wheat germ), peroxidase labeled, was placed into these functionally defined subregions to label anterogradely the terminals of axons that originated in the FEF. Our results demonstrate that both the FEFsem and FEFsac send direct projections to the ipsilateral riMLF. The distribution and density of labeling from the FEFsem are comparable to those from the FEFsac. The direct FEFsem-to-riMLF projection suggests a possible role of the riMLF in smooth pursuit eye movements and supports the hypothesis that there is interaction between the saccadic and pursuit subsystems at the brain stem level.
Receptive Fields and Response Properties of Neurons in the Star-Nosed Mole's Somatosensory Fovea
Authors: Sachdev Robert N. S. , Catania Kenneth C.
Published: December 2017

Star-nosed moles have an extraordinary mechanosensory system consisting of 22 densely innervated nasal appendages covered with thousands of sensitive touch domes. A single appendage acts as the fovea and the star is constantly shifted to touch this foveal appendage to objects of interest. Here we investigated the receptive fields on the star and the response properties of 144 neurons in the mole's primary somatosensory cortex (S1). Excitatory receptive fields were defined by recording multiunit activity from the S1 representations of the nasal appendages that form the star, while stimulating the touch domes on the skin surface with a small probe. Receptive fields were among the smallest reported for mammalian glabrous skin, averaging <1 mm2. The smallest receptive fields were found for the fovea representation, corresponding to its greater cortical magnification. Single units were then isolated, primarily from the representation of the somatosensory fovea, and the skin surface was stimulated with a small probe attached to a piezoelectric wafer controlled by a computer interface. The response properties of neurons and the locations of inhibitory surrounds were evaluated with two complementary approaches. In the first set of experiments, single microelectrodes were used to isolate unit activity in S1, and data were collected for stimulation to different areas of the sensory star. In the second set of experiments, a multi-electrode array (4 electrodes spaced at 200 μm in a linear sequence) was used to simultaneously record from isolated units in different cortical areas representing different parts of the sensory periphery. These experiments revealed a short-latency excitatory discharge to stimulation of the fovea followed by a long-lasting suppression of spontaneous activity. Sixty-one percent of neurons responded with an excitatory off response at the end of the stimulus; the remaining 39% of cells did not respond or were inhibited at stimulus offset. Stimulation of areas surrounding the central receptive field often revealed inhibitory surrounds. Forty percent of the neurons that responded to mechanosensory stimulation of the receptive field center were inhibited by stimulation of surrounding areas of skin on the same appendage. In contrast to neurons in rodent barrels, few neurons within a stripe representing an appendage responded to stimulation of neighboring (nonprimary) appendages on the snout. The small receptive fields, short latencies, and inhibitory surrounds are consistent with the star's role in rapidly determining the locations and identities of objects in a complex tactile environment.
Stimulus-Related Gamma Oscillations in Primate Auditory Cortex
Authors: Brosch Michael , Budinger Eike , Scheich Henning
Published: December 2017

With a multielectrode system, we explored neuronal activity in the γ range (>40 Hz) in the primary and caudomedial auditory cortex of six anesthetized macaque monkeys. Stimuli were tone bursts of 100- to 500-ms duration that were presented at sound pressure levels of 40–60 dB and were varied over a wide range of frequencies. These stimuli induced γ oscillations, not phase-locked to the onset of stimulation, in 465 of 616 multiunit clusters and at 321 of 422 sites at which field potentials were recorded. Occurrence of γ activity was stimulus dependent. It was mostly seen when the stimulus was at the units' preferred frequency. The incidence of γ activity decreased with increasing difference between stimulus frequency and preferred frequency. γ activity emerged 100–900 ms after stimulus onset with highest incidence ∼120 ms. Amplitudes of stimulus-induced γ oscillations in field potentials were, on average, almost twice the amplitude of spontaneously occurring γ oscillations. γ activity at different sites within the primary and the caudomedial auditory field could be synchronized at near-zero phase. Synchrony depended on the spatial distance and on the receptive fields similarity of pairs of units. It decreased with increasing distance between recording sites and increased with similarity of preferred frequencies of the pairs of units. The results indicate that stimulus-induced γ oscillations originate from sources in the auditory cortex. They further suggest that γ oscillations may provide a mechanism utilized in many parts of the sensory cortex, including the auditory cortex, to integrate neurons according to the similarity of their receptive fields.