bluuebunny/crossref_metadata_2025 huggingface dataset:
Temporal Frequency of Whisker Movement. I. Representations in Brain Stem and Thalamus
Authors: Sosnik Ronen , Haidarliu Sebastian , Ahissar Ehud
Published: December 2017

How does processing of information change the internal representations used in subsequent stages of sensory pathways? To approach this question, we studied the representations of whisker movements in the lemniscal and paralemniscal pathways of the rat vibrissal system. We recently suggested that these two pathways encode movement frequency in different ways. We proposed that paralemniscal thalamocortical circuits, functioning as phase-locked loops (PLLs), translate temporally coded information into a rate code. Here we focus on the two major trigeminal nuclei of the brain stem, nucleus principalis and subnucleus interpolaris, and on their thalamic targets, the ventral posteromedial nucleus (VPM) and the medial division of the posterior nucleus (POm). This is the first study in which these brain stem and thalamic nuclei were explored together in the same animals and using the same stimuli. We studied both single- and multi-unit activity. We moved the whiskers both mechanically and by air puffs; here we present air-puff-induced movements because they are more similar to natural movements than movements induced by mechanical stimulations. We describe the basic properties of the responses in these brain stem and thalamic nuclei. The responses in both brain stem nuclei were similar; responses to air puffs were mostly tonic and followed the trajectory of whisker movement. The responses in the two thalamic nuclei were similar during low-frequency stimulations or during the first pulses of high-frequency stimulations, exhibiting more phasic responses than those of brain stem neurons. However, with frequencies >2 Hz, VPM and POm responses differed, generating different representations of the stimulus frequency. In the VPM, response amplitudes (instantaneous firing rates) and spike counts (total number of spikes per stimulus cycle) decreased as a function of the frequency. In the POm, latencies increased and spike count decreased as a function of the frequency. Having described the basic response properties in the four nuclei, we then focus on a specific test of our PLL hypothesis for coding in the paralemniscal pathway. We used short-duration air puffs, much shorter than whisker movements during natural whisking. The activity in this situation was consistent with the prediction we made on the basis of the PLL hypothesis.
Persistent Na+ Current and Ca2+ Current Boost Graded Depolarization of Rat Retinal Amacrine Cells in Culture
Authors: Koizumi Amane , Watanabe Shu-Ichi , Kaneko Akimichi
Published: December 2017

Retinal amacrine cells are depolarized by the excitatory synaptic input from bipolar cells. When a graded depolarization exceeds the threshold level, trains of action potentials are generated. There have been several reports that both spikes and graded depolarization are sensitive to tetrodotoxin (TTX). In the present study, we investigated the contribution of voltage-gated currents to membrane depolarization by using rat GABAergic amacrine cells in culture recorded by the patch-clamp method. Injection of a negative current induced membrane hyperpolarization, the waveform of which can be well fitted by a single exponential function. Injection of positive current depolarized the cell, and the depolarization exceeded the amplitude expected from the passive properties of the membrane. The boosted depolarization sustained after the current was turned off. Either 1 μM TTX or 2 mM Co2+ suppressed the boosted depolarization, and co-application of TTX and Co2+ blocked it completely. Under the voltage clamp, we identified a transient Na+ current (fast I Na), a TTX-sensitive persistent current that reversed the polarity near the equilibrium potential of Na+ ( I NaP), and three types of Ca2+ currents ( I Ca), L, N, and the pharmacological agent-resistant type (R type). These findings suggest that the I NaP and I Ca of amacrine cells boost depolarization evoked by the excitatory synaptic input, and they may aid the spread of electrical signals among dendritic arbors of amacrine cells.
Rhythmicity of Spinal Neurons Activated During Each Form of Fictive Scratching in Spinal Turtles
Authors: Berkowitz Ari
Published: December 2017

Are behaviors that rely on common muscles and motoneurons generated by separate or overlapping groups of pattern-generating neurons? This question was investigated for the three forms of scratching in immobilized, spinal turtles. Individual neurons were recorded extracellularly from the gray matter through most of the spinal cord hindlimb enlargement gray matter, but were avoided in the region of motoneuron cell bodies. Each form of fictive scratching was elicited by mechanical stimulation of the body surface. The rhythmic modulation of spinal neurons was assessed using phase histograms and circular statistics. The degree of rhythmic modulation and the phase preference of each rhythmically active neuron were measured with respect to the activity cycle of the ipsilateral hip flexor nerve. The action potentials of rhythmic neurons tended to be concentrated in a particular phase of the ipsilateral hip flexor activity cycle no matter which form of fictive scratching was elicited. This consistent phase preference suggests that some of these neurons may contribute to generation of the hip rhythm for all three forms of scratching, strengthening the case that vertebrate pattern-generating circuitry for distinct behaviors can be overlapping. The degree of rhythmic modulation of each unit during fictive scratching was consistently correlated with the dorsoventral location of the recording, but not with the mediolateral or rostrocaudal location; neurons located more ventrally tended to be more rhythmic. The phase preferences of units were related to the region of the body surface to which each neuron responded maximally (i.e., the region to which each unit was broadly tuned). Units tuned to the rostral scratch or pocket scratch region tended to have a phase preference during ipsilateral hip flexor activity, whereas units tuned to the caudal scratch region did not. This suggests the hypothesis that the hip flexes further during rostral and pocket scratching, and extends further during caudal scratching, due to the net effects of a population of spinal interneurons that are both broadly tuned and rhythmically active.
Abundant GFP Expression and LTP in Hippocampal Acute Slices by In Vivo Injection of Sindbis Virus
Authors: D'Apuzzo Massimo , Mandolesi Georgia , Reis Gerald , Schuman Erin M.
Published: December 2017

Virus-mediated gene transfer into neurons is a powerful tool for the analysis of neuronal structure and function. Recombinant sindbis virus has been previously used to study protein function in hippocampal neuron cultures as well as in hippocampal organotypic slice cultures. Nevertheless, some concern still exists about the physiological relevance of these cultured preparations. Acute hippocampal slices are a widely used preparation for the study of synaptic transmission, but currently recombinant gene delivery is usually achieved only through time-consuming transgenic techniques. In this study, we show that a subregion of the CA1 area in acute hippocampal slices can be specifically altered to express a gene of interest. A sindbis virus vector carrying an enhanced green fluorescent protein (EGFP) reporter was injected in vivo into the hippocampus of adult rats. After 18 h, rats were killed, and acute hippocampal slices, infected in the CA1 field, were analyzed morphologically and electrophysiologically. Infected slices showed healthy and stable electrophysiological responses as well as long-term potentiation. In addition, infected pyramidal cells were readily recognized in living slices by two-photon imaging. Specifically, the introduction of an EGFP-Actin fusion protein greatly enhanced the detection of fine processes and dendritic spines. We propose this technique as an efficient tool for studying gene function in adult hippocampal neurons.
Impedance Control and Internal Model Formation When Reaching in a Randomly Varying Dynamical Environment
Authors: Takahashi C. D. , Scheidt R. A. , Reinkensmeyer D. J.
Published: December 2017

We investigated the effects of trial-to-trial, random variation in environmental forces on the motor adaptation of human subjects during reaching. Novel sequences of dynamic environments were applied to subjects' hands by a robot. Subjects reached first in a “mean field” having a constant gain relating force and velocity, then in a “noise field,” having a gain that varied randomly between reaches according to a normal distribution with a mean identical to that of the mean field. The unpredictable nature of the noise field did not degrade adaptation as quantified by final kinematic error and rate of adaptation. To achieve this performance, the nervous system used a dual strategy. It increased the impedance of the arm as evidenced by a significant reduction in aftereffect size following removal of the noise field. Simultaneously, it formed an internal model of the mean of the random environment, as evidenced by a minimization of trajectory error on trials for which the noise field gain was close to the mean field gain. We conclude that the human motor system is capable of predicting and compensating for the dynamics of an environment that varies substantially and randomly from trial to trial, while simultaneously increasing the arm's impedance to minimize the consequence of errors in the prediction.
Contribution of Nav1.8 Sodium Channels to Action Potential Electrogenesis in DRG Neurons
Authors: Renganathan Muthukrishnan , Cummins Theodore R. , Waxman Stephen G.
Published: December 2017

C-type dorsal root ganglion (DRG) neurons can generate tetrodotoxin-resistant (TTX-R) sodium-dependent action potentials. However, multiple sodium channels are expressed in these neurons, and the molecular identity of the TTX-R sodium channels that contribute to action potential production in these neurons has not been established. In this study, we used current-clamp recordings to compare action potential electrogenesis in Nav1.8 (+/+) and (−/−) small DRG neurons maintained for 2–8 h in vitro to examine the role of sodium channel Nav1.8 (α-SNS) in action potential electrogenesis. Although there was no significant difference in resting membrane potential, input resistance, current threshold, or voltage threshold in Nav1.8 (+/+) and (−/−) DRG neurons, there were significant differences in action potential electrogenesis. Most Nav1.8 (+/+) neurons generate all-or-none action potentials, whereas most of Nav1.8 (−/−) neurons produce smaller graded responses. The peak of the response was significantly reduced in Nav1.8 (−/−) neurons [31.5 ± 2.2 (SE) mV] compared with Nav1.8 (+/+) neurons (55.0 ± 4.3 mV). The maximum rise slope was 84.7 ± 11.2 mV/ms in Nav1.8 (+/+) neurons, significantly faster than in Nav1.8 (−/−) neurons where it was 47.2 ± 1.3 mV/ms. Calculations based on the action potential overshoot in Nav1.8 (+/+) and (−/−) neurons, following blockade of Ca2+ currents, indicate that Nav1.8 contributes a substantial fraction (80–90%) of the inward membrane current that flows during the rising phase of the action potential. We found that fast TTX-sensitive Na+ channels can produce all-or-none action potentials in some Nav1.8 (−/−) neurons but, presumably as a result of steady-state inactivation of these channels, electrogenesis in Nav1.8 (−/−) neurons is more sensitive to membrane depolarization than in Nav1.8 (+/+) neurons, and, in the absence of Nav1.8, is attenuated with even modest depolarization. These observations indicate that Nav1.8 contributes substantially to action potential electrogenesis in C-type DRG neurons.
Resonance of Spike Discharge Modulation in Neurons of the Guinea Pig Medial Vestibular Nucleus
Authors: Ris L. , Hachemaoui M. , Vibert N. , Godaux E. , Vidal P. P. , Moore L. E.
Published: December 2017

The modulation of action potential discharge rates is an important aspect of neuronal information processing. In these experiments, we have attempted to determine how effectively spike discharge modulation reflects changes in the membrane potential in central vestibular neurons. We have measured how their spike discharge rate was modulated by various current inputs to obtain neuronal transfer functions. Differences in the modulation of spiking rates were observed between neurons with a single, prominent after hyperpolarization (AHP, type A neurons) and cells with more complex AHPs (type B neurons). The spike discharge modulation amplitudes increased with the frequency of the current stimulus, which was quantitatively described by a neuronal model that showed a resonance peak >10 Hz. Modeling of the resonance peak required two putative potassium conductances whose properties had to be markedly dependent on the level of the membrane potential. At low frequencies (≤0.4 Hz), the gain or magnitude functions of type A and B discharge rates were similar relative to the current input. However, resting input resistances obtained from the ratio of the membrane potential and current were lower in type B compared with type A cells, presumably due to a higher level of active potassium conductances at rest. The lower input resistance of type B neurons was compensated by a twofold greater sensitivity of their firing rate to changes in membrane potential, which suggests that synaptic inputs on their dendritic processes would be more efficacious. This increased sensitivity is also reflected in a greater ability of type B neurons to synchronize with low-amplitude sinusoidal current inputs, and in addition, their responses to steep slope ramp stimulation are enhanced over the more linear behavior of type A neurons. This behavior suggests that the type B MVNn are moderately tuned active filters that promote high-frequency responses and that type A neurons are like low-pass filters that are well suited for the resting tonic activity of the vestibular system. However, the more sensitive and phasic type B neurons contribute to both low- and high-frequency control as well as signal detection and would amplify the contribution of both irregular and regular primary afferents at high frequencies.
Activity in Rostral Motor Cortex in Response to Predictable Force-Pulse Perturbations in a Precision Grip Task
Authors: Boudreau Marie-Josée , Smith Allan M.
Published: December 2017

The purpose of this investigation was to characterize the discharge of neurons in the rostral area 4 motor cortex (MI) during performance of a precision grip task. Three monkeys were trained to grasp an object between the thumb and index finger and to lift and hold it stationary for 2–2.5 s within a narrow position window. The grip and load forces and the vertical displacement of the object were recorded on each trial. On some trials a downward force-pulse perturbation generating a shear force and slip on the skin was applied to the object after 1.5 s of static holding. In total, 72 neurons were recorded near the rostral limit of the hand area of the motor cortex, located close to the premotor areas. Of these, 30 neurons were examined for receptive fields, and all 30 were found to receive proprioceptive inputs from finger muscles. Intracortical microstimulation applied to 38 recording sites evoked brief hand movements, most frequently involving the thumb and index finger with an average threshold of 12 μA. Slightly more than one-half of the neurons (38/72) demonstrated significant increases in firing rate that on average began 284 ± 186 ms before grip onset. Of 54 neurons tested with predictable force-pulse perturbations, 29 (53.7%) responded with a reflexlike reaction at a mean latency of 54.2 ± 16.8 ms. This latency was 16 ms longer than the mean latency of reflexlike activity evoked in neurons with proprioceptive receptive fields in the more caudal motor cortex. No neurons exhibited anticipatory activity that preceded the perturbation even when the perturbations were delivered randomly and signaled by a warning stimulus. The results indicate the presence of a strong proprioceptive input to the rostral motor cortex, but raise the possibility that the afferent pathway or intracortical processing may be different because of the slightly longer latency.
Persistent TTX-Resistant Na+Current Affects Resting Potential and Response to Depolarization in Simulated Spinal Sensory Neurons
Authors: Herzog R. I. , Cummins T. R. , Waxman S. G.
Published: December 2017

Small dorsal root ganglion (DRG) neurons, which include nociceptors, express multiple voltage-gated sodium currents. In addition to a classical fast inactivating tetrodotoxin-sensitive (TTX-S) sodium current, many of these cells express a TTX-resistant (TTX-R) sodium current that activates near −70 mV and is persistent at negative potentials. To investigate the possible contributions of this TTX-R persistent (TTX-RP) current to neuronal excitability, we carried out computer simulations using the Neuron program with TTX-S and -RP currents, fit by the Hodgkin-Huxley model, that closely matched the currents recorded from small DRG neurons. In contrast to fast TTX-S current, which was well fit using a m3h model, the persistent TTX-R current was not well fit by an m3h model and was better fit using an mh model. The persistent TTX-R current had a strong influence on resting potential, shifting it from −70 to −49.1 mV. Inclusion of an ultra-slow inactivation gate in the persistent current model reduced the potential shift only slightly, to −56.6 mV. The persistent TTX-R current also enhanced the response to depolarizing inputs that were subthreshold for spike electrogenesis. In addition, the presence of persistent TTX-R current predisposed the cell to anode break excitation. These results suggest that, while the persistent TTX-R current is not a major contributor to the rapid depolarizing phase of the action potential, it contributes to setting the electrogenic properties of small DRG neurons by modulating their resting potentials and response to subthreshold stimuli.
Reorganization in Awake Rat Auditory Cortex by Local Microstimulation and Its Effect on Frequency-Discrimination Behavior
Authors: Talwar Sanjiv K. , Gerstein George L.
Published: December 2017

In common with other sensory cortices, the mammalian primary auditory cortex (AI) demonstrates the capacity for large-scale reorganization following many experimental situations. For example, training animals in frequency-discrimination tasks has been shown to result in an increase in cortical frequency representation. Such central changes—most commonly, an increase in central representation of specific stimulus parameters—have been hypothesized to underlie the improvements in perceptual acuity (perceptual learning) seen in many learning situations. The actual behavioral relevance of central reorganizations, however, remains speculative. Here, we directly examine this issue. We first show that stimulating the AI cortex of the awake rat with a weak electric current (intracortical microstimulation or ICMS) has the effect of inducing central reorganizations similar to those accompanying the traditional plasticity experiments (a result previously noted only in anesthetized preparations). Depending on the site of AI stimulation, ICMS enlarged the cortical representation of certain frequencies. Next we examined the direct perceptual consequences of ICMS-induced AI reorganization for the rat's ability to discriminate frequencies. Over the course of the experiment, we also detailed, and made comparisons between, the frequency-response characteristics of rat AI cortex in the awake and ketamine-anesthetized animal. AI cells that responded to pure tones were divided into two categories—strongly and weakly responsive—based on the strength of their evoked discharge. Individual cells maintained their respective response strengths in both awake and anesthetized conditions. Strongly responsive cells showed at least four different temporal responses and tended to be narrowly tuned. Their responses were stable over the long term. In general frequency-response characteristics were qualitatively similar in the anesthetized and awake animal; bandwidths tended to be broader in awake animals. Although both strong and weak cell populations respond to tones, only the strongly responsive cells fit into a tonotopically organized scheme. By contrast, weakly responsive cells did not exhibit a frequency mapping and may represent a more diffuse input to AI than that underlying strongly responsive cells. In general, the overall frequency organization of AI was found to be equally well expressed in both the awake and anesthetized rat. ICMS reorganization of AI did not alter frequency-discrimination behavior in the rat—either signal detectability or response bias—suggesting that an increase in central representation, by itself, is insufficient to account for perceptual learning. It is likely that cortical reorganizations that accompany perceptual learning are strongly keyed to specific behavioral contexts.
Function of NMDA Receptors and Persistent Sodium Channels in a Feedback Pathway of the Electrosensory System
Authors: Berman Neil , Dunn Robert J. , Maler Leonard
Published: December 2017

Voltage-dependent amplification of ionotropic glutamatergic excitatory postsynaptic potentials (EPSPs) can, in many vertebrate neurons, be due either to the intrinsic voltage dependence of N-methyl-d-aspartate (NMDA) receptors, or voltage-dependent persistent sodium channels expressed on postsynaptic dendrites or somata. In the electrosensory lateral line lobe (ELL) of the gymnotiform fish Apteronotus leptorhynchus,glutamatergic inputs onto pyramidal cell apical dendrites provide a system where both amplification mechanisms are possible. We have now examined the roles for both NMDA receptors and sodium channels in the control of EPSP amplitude at these synapses. An antibody specific for the A. leptorhynchus NR1 subunit reacted strongly with ELL pyramidal cells and were particularly abundant in the spines of pyramidal cell apical dendrites. We have also shown that NMDA receptors contributed strongly to the late phase of EPSPs evoked by stimulation of the feedback fibers terminating on the apical dendritic spines; further, these EPSPs were voltage dependent. Blockade of NMDA receptors did not, however, eliminate the voltage dependence of these EPSPs. Blockade of somatic sodium channels by local somatic ejection of tetrodotoxin (TTX), or inclusion of QX314 (an intracellular sodium channel blocker) in the recording pipette, reduced the evoked EPSPs and completely eliminated their voltage dependence. We therefore conclude that, in the subthreshold range, persistent sodium currents are the main contributor to voltage-dependent boosting of EPSPs, even when they have a large NMDA receptor component.
Greater Movement-Related Cortical Potential During Human Eccentric Versus Concentric Muscle Contractions
Authors: Fang Yin , Siemionow Vlodek , Sahgal Vinod , Xiong Fuqin , Yue Guang H.
Published: December 2017

Despite abundant evidence that different nervous system control strategies may exist for human concentric and eccentric muscle contractions, no data are available to indicate that the brain signal differs for eccentric versus concentric muscle actions. The purpose of this study was to evaluate electroencephalography (EEG)-derived movement-related cortical potential (MRCP) and to determine whether the level of MRCP-measured cortical activation differs between the two types of muscle activities. Eight healthy subjects performed 50 voluntary eccentric and 50 voluntary concentric elbow flexor contractions against a load equal to 10% body weight. Surface EEG signals from four scalp locations overlying sensorimotor-related cortical areas in the frontal and parietal lobes were measured along with kinetic and kinematic information from the muscle and joint. MRCP was derived from the EEG signals of the eccentric and concentric muscle contractions. Although the elbow flexor muscle activation (EMG) was lower during eccentric than concentric actions, the amplitude of two major MRCP components—one related to movement planning and execution and the other associated with feedback signals from the peripheral systems—was significantly greater for eccentric than for concentric actions. The MRCP onset time for the eccentric task occurred earlier than that for the concentric task. The greater cortical signal for eccentric muscle actions suggests that the brain probably plans and programs eccentric movements differently from concentric muscle tasks.
Surround Suppression in Primate V1
Authors: Jones H. E. , Grieve K. L. , Wang W. , Sillito A. M.
Published: December 2017

We investigated the spatial organization of surround suppression in primate primary visual cortex (V1). We utilized drifting stimuli, configured to extend either from within the classical receptive field (CRF) to surrounding visual space, or from surrounding visual space into the CRF or subdivided to generate direction contrast, to make a detailed examination of the strength, spatial organization, direction dependence, mechanisms, and laminar distribution of surround suppression. Most cells (99/105, 94%) through all cortical layers, exhibited suppression (mean reduction 67%) to uniform stimuli exceeding the CRF, and 43% exhibited a more than 70% reduction. Testing with an annulus revealed two different patterns of surround influence. Some cells (37% of cells), classical surround suppression (CSS) cells exhibited responses to an annulus encroaching on the CRF that were less than the plateau in the spatial summation curve. The majority (63%), center-gated surround suppression (CGSS) cells, showed responses to annuli that equaled or exceeded the plateau in the spatial summation curve. Analysis suggested the CSS mechanism was implemented in all cells while the CGSS mechanism was implemented in varying strength across the sample with the extreme reflected in cells that gave larger responses to annuli than to a center stimulus. Reversing the direction of motion of the portion of the stimulus surrounding the CRF revealed four different patterns of effect: no reduction in the degree of suppression (22% of cells), a reduction in surround suppression (41%), a facilitation of the response above the level to the inner stimulus alone (37%), and a facilitation of the response above that to the inner stimulus alone that also exceeded the values associated with an optimal inner stimulus. The facilitatory effects were only seen for reverse direction interfaces between the central and surrounding stimulus at diameters equal to or more than the CRF size. The zones driving the suppressive influences and the direction contrast facilitation were often spatially heterogeneous and for a number of cells bore strong comparison with the class of behavior reported for surround mechanisms in MT. This suggests a potential role, for example, in extracting information about motion contrast in the representation of the three dimensional structure of moving objects.
Neural Activity in Primary Motor Cortex Related to Mechanical Loads Applied to the Shoulder and Elbow During a Postural Task
Authors: Cabel D. William , Cisek Paul , Scott Stephen H.
Published: December 2017

Whole-arm motor tasks performed by nonhuman primates have become a popular paradigm to examine neural activity during motor action, but such studies have traditionally related cell discharge to hand-based variables. We have developed a new robotic device that allows the mechanics of the shoulder and elbow joints to be manipulated independently. This device was used in the present study to examine neural activity in primary motor cortex (MI) in monkeys ( macaca mulatta) actively maintaining their hand at a central target as they compensated for loads applied to the shoulder and/or elbow. Roughly equal numbers of neurons were sensitive to mechanical loads only at the shoulder, only at the elbow, or loads at both joints. Neurons possessed two important properties. First, cell activity during multi-joint loads could be predicted from its activity during single-joint loads as a vector sum in a space defined by orthogonal axes for the shoulder and elbow. Second, most neurons were related to flexor torque at one joint coupled with extensor torque at the other, a distribution that paralleled the observed activity of forelimb muscles. These results illustrate that while MI activity may be described by independent axes representing each mechanical degree-of-freedom, neural activity is also strongly influenced by the specific motor patterns used to perform a given task.
Shape Representation in Area V4: Position-Specific Tuning for Boundary Conformation
Authors: Pasupathy Anitha , Connor Charles E.
Published: December 2017

Visual shape recognition in primates depends on a multi-stage pathway running from primary visual cortex (V1) to inferotemporal cortex (IT). The mechanisms by which local shape signals from V1 are transformed into selectivity for abstract object categories in IT are unknown. One approach to this issue is to investigate shape representation at intermediate stages in the pathway, such as area V4. We studied 109 V4 cells that appeared sensitive to complex shape in preliminary tests. To achieve a more complete picture of shape representation in V4, we tested each cell with a set of 366 stimuli, constructed by systematically combining convex and concave boundary elements into closed shapes. Using this large, diverse stimulus set, we found that all the cells in our sample responded to a wide variety of shapes and did not appear to encode any single type of global shape. However, for most cells the shapes evoking strongest responses were characterized by a consistent type of boundary conformation at a specific position within the stimulus. For example, a given cell might be tuned for shapes containing concave curvature at the right, with other parts of the shape having little or no effect on responses. Many cells were tuned for more complex boundary configurations (e.g., a convex angle adjacent to a concave curve). We quantified this kind of shape tuning with Gaussian functions on a curvature × position domain. These tuning functions fit the neural responses much better than tuning functions based on edge or axis orientation. Thus individual V4 cells appear to encode moderately complex boundary information at specific locations within larger shapes. This finding suggests that, at intermediate stages in the V1-IT transformation, complex objects are represented at least partly in terms of the configurations and positions of their contour components.
Neural Representation of the Luminance and Brightness of a Uniform Surface in the Macaque Primary Visual Cortex
Authors: Kinoshita Masaharu , Komatsu Hidehiko
Published: December 2017

The perceived brightness of a surface is determined not only by the luminance of the surface (local information), but also by the luminance of its surround (global information). To better understand the neural representation of surface brightness, we investigated the effects of local and global luminance on the activity of neurons in the primary visual cortex (V1) of awake macaque monkeys. Single- and multiple-unit recordings were made from V1 while the monkeys were performing a visual fixation task. The classical receptive field of each neuron was identified as a region responding to a spot stimulus. Neural responses were assessed using homogeneous surfaces at least three times as large as the receptive field as stimuli. We first examined the sensitivity of neurons to variation in local surface luminance, while the luminance of the surround was held constant. The activity of a large majority of surface-responsive neurons (106/115) varied monotonically with changes in surface luminance; in some the dynamic range was over 3 log units. This monotonic relation between surface luminance and neural activity was more evident later in the stimulus period than early on. The effect of the global luminance on neural activity was then assessed in 81 of the surface-responsive neurons by varying the luminance of the surround while holding the luminance of the surface constant. The activity of one group of neurons (25/81) was unaffected by the luminance of the surround; these neurons appear to encode the physical luminance of a surface covering the receptive field. The responses of the other neurons were affected by the luminance of the surround. The effects of the luminances of the surface and the surround on the activities of 26 of these neurons were in the same direction (either increased or decreased), while the effects on the remaining 25 neurons were in opposite directions. The activities of the latter group of neurons seemed to parallel the perceived brightness of the surface, whereas the former seemed to encode the level of illumination. There were differences across different types of neurons with regard to the layer distribution. These findings indicate that global luminance information significantly modulates the activity of surface-responsive V1 neurons and that not only physical luminance, but also perceived brightness, of a homogeneous surface is represented in V1.
A Novel Pharmacological Probe Links the Amiloride-Insensitive NaCl, KCl, and NH4Cl Chorda Tympani Taste Responses
Authors: DeSimone John A. , Lyall Vijay , Heck Gerard L. , Phan Tam-Hao T. , Alam Rammy I. , Feldman George M. , Buch R. Michael
Published: December 2017

Chorda tympani taste nerve responses to NaCl can be dissected pharmacologically into amiloride-sensitive and -insensitive components. It is now established that the amiloride-sensitive, epithelial sodium channel acts as a sodium-specific ion detector in taste receptor cells (TRCs). Much less is known regarding the cellular origin of the amiloride-insensitive component, but its anion dependence indicates an important role for paracellular shunts in the determination of its magnitude. However, this has not precluded the possibility that undetected apical membrane ion pathways in TRCs may also contribute to its origin. Progress toward making such a determination has suffered from lack of a pharmacological probe for an apical amiloride-insensitive taste pathway. We present data here showing that, depending on the concentration used, cetylpyridinium chloride (CPC) can either enhance or inhibit the amiloride-insensitive response to NaCl. The CPC concentration giving maximal enhancement was 250 μM. At 2 mM, CPC inhibited the entire amiloride-insensitive part of the NaCl response. The NaCl response is, therefore, composed entirely of amiloride- and CPC-sensitive components. The magnitude of the maximally enhanced CPC-sensitive component varied with the NaCl concentration and was half-maximal at [NaCl] = 62 ± 11 (SE) mM. This was significantly less than the corresponding parameter for the amiloride-sensitive component (268 ± 71 mM). CPC had similiar effects on KCl and NH4Cl responses except that in these cases, after inhibition with 2 mM CPC, a significant CPC-insensitive response remained. CPC (2 mM) inhibited intracellular acidification of TRCs due to apically presented NH4Cl, suggesting that CPC acts on an apical membrane nonselective cation pathway.
Biphasic Modulation of Spinal Visceral Nociceptive Transmission From the Rostroventral Medial Medulla in the Rat
Authors: Zhuo M. , Sengupta J. N. , Gebhart G. F.
Published: December 2017

Descending inhibitory and facilitatory influences from the rostroventral medulla (RVM) on responses of lumbosacral spinal neurons to noxious colorectal distension (CRD, 80 mmHg, 20 s) were studied. At 25 sites in the RVM, electrical stimulation produced biphasic effects, facilitating responses of spinal neurons to CRD at lesser intensities of stimulation (5–25 μA) and inhibiting responses of the same neurons at greater intensities of stimulation (50–100 μA). At 38 other sites in the RVM, electrical stimulation produced only intensity-dependent inhibition of neuron responses to CRD. At another 13 sites in the RVM, electrical stimulation (5–100 μA) produced only facilitatory effects on responses to CRD. Descending modulatory effects were selective for distension-evoked activity; spontaneous activities of the same spinal neurons were not significantly affected by electrical stimulation that either facilitated or inhibited neuron responses to CRD. Neuron responses to graded CRD (20–100 mmHg) were positively accelerating functions that were shifted leftward or rightward, respectively, by lesser, facilitatory intensities or greater, inhibitory intensities of RVM stimulation. l-glutamate microinjection into the RVM replicated the effects of electrical stimulation, producing similar biphasic modulatory effects as produced by electrical stimulation. Microinjection of glutamate into the RVM at a low dose (5 nmoles) facilitated responses of spinal neurons to CRD and inhibited responses of the same neurons at a greater dose (50 nmoles). In some experiments, microinjection of lidocaine (0.5 μl of 4% solution) or the neurotoxin ibotenic acid (0.5 μl, 10 μg) into the RVM produced reversible or long-lasting, respectively, decreases in spontaneous activity and responses of spinal neurons to CRD. These results reveal that spinal visceral nociceptive transmission is subject to a tonic descending excitatory influence from the RVM and that descending modulatory effects from the RVM on visceral nociceptive transmission are qualitatively similar to modulation of cutaneous nociceptive transmission.
Neural Representations of Sinusoidal Amplitude and Frequency Modulations in the Primary Auditory Cortex of Awake Primates
Authors: Liang Li , Lu Thomas , Wang Xiaoqin
Published: December 2017

We investigated neural coding of sinusoidally modulated tones (sAM and sFM) in the primary auditory cortex (A1) of awake marmoset monkeys, demonstrating that there are systematic cortical representations of embedded temporal features that are based on both average discharge rate and stimulus-synchronized discharge patterns. The rate-representation appears to be coded alongside the stimulus-synchronized discharges, such that the auditory cortex has access to both rate and temporal representations of the stimulus at high and low frequencies, respectively. Furthermore, we showed that individual auditory cortical neurons, as well as populations of neurons, have common features in their responses to both sAM and sFM stimuli. These results may explain the similarities in the perception of sAM and sFM stimuli as well as the different perceptual qualities effected by different modulation frequencies. The main findings include the following. 1) Responses of cortical neurons to sAM and sFM stimuli in awake marmosets were generally much stronger than responses to unmodulated tones. Some neurons responded to sAM or sFM stimuli but not to pure tones. 2) The discharge rate-based modulation transfer function typically had a band-pass shape and was centered at a preferred modulation frequency (rBMF). Population-averaged mean firing rate peaked at 16- to 32-Hz modulation frequency, indicating that the A1 was maximally excited by this frequency range of temporal modulations. 3) Only approximately 60% of recorded units showed statistically significant discharge synchrony to the modulation waveform of sAM or sFM stimuli. The discharge synchrony-based best modulation frequency (tBMF) was typically lower than the rBMF measured from the same neuron. The distribution of rBMF over the population of neurons was approximately one octave higher than the distribution of tBMF. 4) There was a high degree of similarity between cortical responses to sAM and sFM stimuli that was reflected in both discharge rate- or synchrony-based response measures. 5) Inhibition appeared to be a contributing factor in limiting responses at modulation frequencies above the rBMF of a neuron. And 6) neurons with shorter response latencies tended to have higher tBMF and maximum discharge synchrony frequency than those with longer response latencies. rBMF was not significantly correlated with the minimum response latency.
Noradrenaline Increases High-Frequency Firing at the Calyx of Held Synapse During Development by Inhibiting Glutamate Release
Authors: Leão Ricardo M. , Von Gersdorff Henrique
Published: December 2017

The mammalian auditory brain stem receives profuse adrenergic innervation, whose function is poorly understood. Here we investigate, during postnatal development, the effect of noradrenaline (NA) at the calyx of Held synapse in the rat medial nucleus of the trapezoid body (MNTB). We observed that NA inhibits the large glutamatergic EPSC, evoked by afferent fiber stimulation, in a dose-dependent manner. The inhibition was maximal (approximately 48%) at the concentration of 2 μM. It was antagonized by yohimbine and mimicked by the α2-adrenergic specific agonist UK14304. Both AMPA and NMDA receptor-mediated EPSCs were inhibited in parallel by NA, suggesting a presynaptic effect. Presynaptic recordings showed that NA inhibits the action potential (AP) generated Ca current by about 20%; however, NA did not significantly affect the presynaptic AP waveform. We thus conclude that the calyx of Held presynaptic terminal expresses α2-adrenergic receptors that inhibit its Ca current and thus glutamate release. Noradrenaline was effective in all cells tested from postnatal days 6 to 7 (P6–P7), and thereafter the number of responsive cells diminished, although half of the P14 cells tested still had EPSCs that were inhibited by NA. By contrast, activation byl-2-amino-5-phosphonovaleric acid-sensitive metabotropic glutamate receptors strongly inhibited the EPSCs of all cells tested from P6 to P14. The effect of NA on postsynaptic action potential firing was dependent on the stimulus frequency. At 10 Hz, NA had no effect on firing probability; however, NA helped MNTB cells fire more action potentials during a 100-Hz train of stimuli, even though it did not increase the steady-state depressed EPSC, because it produced a smaller N-methyl-d-aspartate (NMDA) receptor-activated depolarizing plateau. We therefore suggest that the reduction by NA of the first few EPSCs in a train leads to a smaller NMDA depolarizing plateau and thus to increased firing probability at 100 Hz in young synapses. Surprisingly, the inhibition of glutamate release by NA can thus actually increase the excitability of MNTB neurons during early postnatal development.
Learning-Induced Enhancement of Postsynaptic Potentials in Pyramidal Neurons
Authors: Saar Drorit , Grossman Yoram , Barkai Edi
Published: December 2017

We studied the effect of olfactory learning-induced modifications in piriform (olfactory) cortex pyramidal neurons on the propagation of postsynaptic potentials (PSPs). Rats were trained to distinguish between odors in pairs, in an olfactory discrimination task. Three days after training completion, PSPs were evoked in layer II pyramidal cells in piriform cortex brain slices by electrical stimulation of two pathways. Stimulation of layer Ib activated the intra-cortical fibers that terminate on the proximal region of the apical and basal dendrites. Stimulation of layer Ia activated the afferent axons that originate from the olfactory bulb and terminate on the distal apical dendrites. We have previously shown that olfactory training is accompanied by enhanced synaptic transmission in the intrinsic pathway, but not in the afferent pathway at 3 days after training. Here we show that at this stage, in both pathways PSPs evoked in neurons from trained rats had significantly faster rise time measured at the soma compared with PSPs in neurons from pseudo-trained and naive rats. Activation of the slow afterhyperpolarization (AHP), which is generated by potassium channels probably located at the proximal region of both apical and basal dendrites, reduced the amplitude measured at the soma of the proximal intrinsic pathway PSPs more effectively than PSPs that were generated distally by the afferent fibers. Thus the amount of reduction by AHP was used as a measure for the relative distance of PSP-generating sites from the soma. In neurons from trained rats, despite the previously reported reduction in AHP amplitude, AHP conductance shunted the PSPs from both synaptic pathways more efficiently compared with neurons from the control rats. We suggest that in neurons from trained rats PSPs are electrotonicly closer to the soma.
Acetylcholine Increases Intracellular Ca2+ in Taste Cells Via Activation of Muscarinic Receptors
Authors: Ogura Tatsuya
Published: December 2017

Previous studies suggest that acetylcholine (ACh) is a transmitter released from taste cells as well as a transmitter in cholinergic efferent neurons innervating taste buds. However, the physiological effects on taste cells have not been established. I examined effects of ACh on taste-receptor cells by monitoring [Ca2+]i. ACh increased [Ca2+]i in both rat and mudpuppy taste cells. Atropine blocked the ACh response, butd-tubocurarine did not. U73122 , a phospholipase C inhibitor, and thapsigargin, a Ca2+-ATPase inhibitor that depletes intracellular Ca2+stores, blocked the ACh response. These results suggest that ACh binds to M1/M3/M5-like subtypes of muscarinic ACh receptors, causing an increase in inositol 1,4,5-trisphosphate and subsequent release of Ca2+ from the intracellular stores. A long incubation with ACh induced a transient response followed by a sustained phase of [Ca2+]i increase. In Ca2+-free solution, the sustained phases disappeared, suggesting that Ca2+ influx is involved in the sustained phase. Depletion of Ca2+ stores by thapsigargin alone induced Ca2+ influx. These findings suggest that Ca2+ store-operated channels may be present in taste cells and that they may participate in the sustained phase of [Ca2+]i increase. Immunocytochemical experiments indicated that the M1 subtype of muscarinic receptors is present in both rat and mudpuppy taste cells.
Hypersensitivity of Spinothalamic Tract Neurons Associated With Diabetic Neuropathic Pain in Rats
Authors: Chen Shao-Rui , Pan Hui-Lin
Published: December 2017

Diabetic neuropathic pain is often considered to be caused by peripheral neuropathy. The involvement of the CNS in this pathological condition has not been well documented. Development of hypersensitivity of spinal dorsal horn neurons is involved in neuropathic pain induced by traumatic nerve injury. In the present study, we determined the functional changes of identified spinothalamic tract (STT) neurons and their correlation to diabetic neuropathic pain. Diabetes was induced in rats by intraperitoneal injection of streptozotocin. Hyperalgesia and allodynia were assessed by the withdrawal responses to pressure, radiant heat, and von Frey filaments applied to the hindpaw. Single-unit activity of STT neurons was recorded from the lumbar spinal cord in anesthetized rats. The responses of STT neurons to mechanical and thermal stimuli and the sensitivity to intravenous morphine were determined in diabetic and normal rats. In 12 diabetic rats, mechanical allodynia and hyperalgesia, but not thermal hyperalgesia, developed within 2 wk after streptozotocin injection and lasted for ≥7 wk. Compared to the 32 STT neurons recorded in normal animals, the 37 STT neurons in diabetic rats displayed a higher spontaneous discharge activity and enlarged receptive fields. Also, the STT neurons in diabetic rats exhibited lower thresholds and augmented responses to mechanical stimulation. Intravenous injection of 2.5 mg/kg of morphine suppressed significantly the responses of STT neurons to noxious stimuli in 12 nondiabetic rats. However, such an inhibitory effect of morphine on the evoked response of STT neurons was diminished in 14 diabetic animals. This electrophysiological study provides new information that development of hypersensitivity of spinal dorsal horn projection neurons may be closely related to neuropathic pain symptoms caused by diabetes. Furthermore, the attenuated inhibitory effects of morphine on evoked responses of STT neurons in diabetes likely accounts for its reduced analgesic efficacy in this clinical form of neuropathic pain.