bluuebunny/crossref_metadata_2025 huggingface dataset:
Expression of protein kinase C isoenzymes α, βI, and δ in subtypes of intercalated cells of mouse kidney
Authors: Kim Wan-Young , Jung Joon-Ho , Park Eun-Young , Yang Chul-Woo , Kim Hyang , Nielsen Søren , Madsen Kirsten M. , Kim Jin
Published: May 2006

Recent studies of the distribution of PKC isoenzymes in the mouse kidney demonstrated that PKC-α, -βI, and -δ are expressed in intercalated cells. The purpose of this study was to identify the intercalated cell subtypes that express the different PKC isoenzymes and determine the location of the PKC isoenzymes within these cells. Adult C57BL/6 mice kidney tissues were processed for multiple-labeling immunohistochemistry. Antibodies against the vacuolar H+-ATPase and pendrin were used to identify intercalated cell subtypes, whereas antibodies against calbindin D28Kand aquaporin-2 (AQP2) were used to identify connecting tubule cells and principal cells of the collecting duct, respectively. Within type A intercalated cells, PKC-δ was highly expressed in the apical part of the cells, whereas immunoreactivity for both PKC-α and PKC-βIwas weak. Type B intercalated cells exhibited strong expression of PKC-α, -βI, and -δ. PKC-α and -βIwere localized throughout the cytoplasm, whereas PKC-δ was restricted to the basal domain. Within non-A-non-B cells, immunoreactivity for both PKC-α and PKC-βIwas high in intensity and localized diffusely in the cytoplasm, whereas PKC-δ was localized in the apical part of the cells. None of the PKC isoenzymes (PKC-α, -βI, or -δ) were expressed in the calbindin D28K-positive connecting tubule cells. Within AQP2-positive principal cells of the collecting duct, PKC-α was expressed on the basolateral plasma membrane, but no significant staining was detected for PKC-βIand -δ. In summary, this study demonstrates distinct and differential expression patterns of PKC-α, -βI, and -δ in the three subtypes of intercalated cells in the mouse kidney.
Metabotropic Receptor-Mediated Ca2+Signaling Elevates Mitochondrial Ca2+and Stimulates Oxidative Metabolism in Hippocampal Slice Cultures
Authors: Kann Oliver , Kovács Richard , Heinemann Uwe
Published: May 2006

Metabotropic receptors modulate numerous cellular processes by intracellular Ca2+signaling, but less is known about their role in regulating mitochondrial metabolic function within the CNS. In this study, we demonstrate in area CA3 of rat organotypic hippocampal slice cultures that glutamatergic, serotonergic, and muscarinic metabotropic receptor ligands, namely trans-azetidine-2,4-dicarboxylic acid, α-methyl-5-hydroxytryptamine, and carbachol, transiently increase mitochondrial Ca2+concentration ([Ca2+]m) as recorded by changes in Rhod-2 fluorescence, stimulate mitochondrial oxidative metabolism as revealed by elevations in NAD(P)H fluorescence, and induce K+outward currents as monitored by rapid increases in extracellular K+concentration ([K+]o). Carbachol (1–1,000 μM) elevated NAD(P)H fluorescence by ≤14%Δ F/ F0and increased [K+]oby ≤4.3 mM in a dose-dependent manner. Carbachol-induced responses persisted in Ca2+-free solution and blockade of ionotropic glutamatergic and nicotinic receptors. Under similar conditions caffeine, known to cause Ca2+-induced Ca2+release (CICR), also evoked elevations in [Ca2+]m, NAD(P)H fluorescence and [K+]othat, in contrast to carbachol-induced responses, displayed oscillations. After depletion of intracellular Ca2+stores by carbachol in Ca2+-free solution, re-application of 1.6 mM Ca2+-containing solution triggered marked elevations in [Ca2+]m, NAD(P)H fluorescence and [K+]o. These data indicate that metabotropic transmission effectively regulates mitochondrial oxidative metabolism via diverse receptor types in hippocampal cells and that inonitol 1,4,5-trisphosphate-induced Ca2+release (IICR) or CICR or capacitative Ca2+entry might suffice in stimulating oxidative metabolism by elevating [Ca2+]m. Thus activation of metabotropic receptors might significantly contribute to generation of ATP within neurons and glial cells.
Surround Modulation Measured With Functional MRI in the Human Visual Cortex
Authors: Williams Adrian L. , Singh Krishna D. , Smith Andrew T.
Published: May 2006

Visual context profoundly influences 1) the responses of mammalian visual neurons and 2) the perceptual sensitivity of human observers to localized visual stimuli. We present data from functional MRI studies demonstrating contextual modulation in the human visual cortex. Subjects viewed a circular grating patch that was continuously present. A surround grating was added in an on–off block design to reveal its effect on the central region. Stimulus-correlated activation was quantified and visualized on a flattened map of the occipital gray matter. Modulation was measured in a region of interest activated by the central grating alone. The observed effects were predominantly suppressive, consistent with the effects typically found in single neurons and perception. Suppression was greatest when the surround and center had the same orientation and was reduced or absent when it was orthogonal. When spatial phase was manipulated, suppression was greatest for in-phase center/surround gratings and much reduced or reversed (facilitation) for opposite-phase stimuli. With eccentric stimulus presentation, suppression was reduced and facilitation became more common. The findings provide a direct demonstration of the existence of powerful and stimulus-specific surround effects in human visual cortex.
Na+-Ca2+Exchanger Controls the Gain of the Ca2+Amplifier in the Dendrites of Amacrine Cells
Authors: Hurtado Jose , Borges Salvador , Wilson Martin
Published: May 2006

We have previously shown that disabling forward-mode Na+-Ca2+exchange in amacrine cells greatly prolongs the depolarization-induced release of transmitter. To investigate the mechanism for this, we imaged [Ca2+]iin segments of dendrites during depolarization. Removal of [Na+]oproduced no immediate effect on resting [Ca2+]ibut did prolong [Ca2+]itransients induced by brief depolarization in both voltage-clamped and unclamped cells. In some cells, depolarization gave rise to stable patterns of higher and lower [Ca2+] over micrometer-length scales that collapsed once [Na+]owas restored. Prolongation of [Ca2+]itransients by removal of [Na+]ois not due to reverse mode operation of Na+-Ca2+exchange but is instead a consequence of Ca2+release from endoplasmic reticulum (ER) stores over which Na+-Ca2+exchange normally exercises control. Even in normal [Na+]o, hotspots for [Ca2+] could be seen following depolarization, that are attributable to local Ca2+-induced Ca2+release. Hotspots were seen to be labile, probably reflecting the state of local stores or their Ca2+release channels. When ER stores were emptied of Ca2+by thapsigargin, [Ca2+] transients in dendrites were greatly reduced and unaffected by the removal of [Na+]oimplying that even when Na+-Ca2+exchange is working normally, the majority of the [Ca2+]iincrease by depolarization is due to internal release rather than influx across the plasma membrane. Na+-Ca2+exchange has an important role in controlling [Ca2+] dynamics in amacrine cell dendrites chiefly by moderating the positive feedback of the Ca2+amplifier.
Effects of Intrathecal Glutamatergic Drugs on Locomotion I. NMDA in Short-Term Spinal Cats
Authors: Chau Connie , Giroux Nathalie , Barbeau Hugues , Jordan Larry , Rossignol Serge
Published: May 2006

Excitatory amino acids (EAA) have been reported to induce fictive locomotion in different in vitro and in vivo preparations in a variety of species through their actions on both N-methyl-d-aspartate (NMDA), and non-NMDA receptors. NMDA-induced intrinsic membrane properties such as intrinsic motoneuronal membrane oscillations and plateau potentials have been suggested to play a role in the generation of locomotion. There is, however, no information on the ability of NMDA in triggering spinal locomotion in awake behaving animals. Because most of the previous work on the induction of locomotion has concentrated on monoaminergic drugs, mainly noradrenergic drugs, the aim of this study is to examine the potential of NMDA in initiating locomotion in chronic spinal cats within the first week after spinalization. Five cats chronically implanted with an intrathecal cannula and electromyographic (EMG) electrodes were used. EMG activity synchronized to video images of the hindlimbs were recorded. The results show that during the early posttransection period (within the 1st week postspinalization), NMDA did not trigger robust locomotion as did noradrenergic drugs. The predominant effects of NMDA were a general hyperexcitability reflected by fast tremor, toe fanning, and an increase in small alternating hindlimb movements with no foot placement nor weight support. During the intermediate phase posttransection (6–8 days), when the cats were able to make some rudimentary steps with foot placement, NMDA significantly enhanced the locomotor performance, which lasted for 24–72 h postinjection. NMDA was also found to increase the excitability of the cutaneous reflex transmission only in early spinal cats. One possible hypothesis for the ineffectiveness of NMDA in triggering locomotion in early spinal cats could be attributed to the widespread activation of NMDA receptors on various neuronal elements involved in the transmission of afferent pathways that in turn may interfere with the expression of locomotion. The marked effects of NMDA in intermediate-spinal cats suggest that NMDA receptors play an important role in locomotion perhaps through its role on intrinsic membrane properties of neurons in shaping and amplifying spinal neuronal transmission or by augmenting the sensory afferent inputs. The long-term effects mediated by NMDA receptors have been reported in the literature and may involve mechanisms such as induction of long-term potentiation or interactions with neuropeptides. The effects of NMDA injection in intact cats and long-term chronic spinal cats will be addressed in a forthcoming companion paper.
Postnatal Development of Corticospinal Postsynaptic Action
Authors: Meng Zhuo , Martin John H.
Published: May 2006

The corticospinal system has a delayed and prolonged postnatal development. In the cat, lesion, inactivation, or stimulation of the system influence motor output minimally when corticospinal (CS) terminals have an immature topographic pattern but produce robust effects immediately after developing the mature pattern by weeks 6–7. In this study, we directly tested if the delay in expression of cortical motor functions is due to the inability of the corticospinal synapse to activate spinal neurons. We stimulated corticospinal axons in the pyramid and recorded evoked field potentials from the surface of the cervical spinal cord and locally from within the gray matter in anesthetized cats during development and in adults. Pyramidal stimulation in animals between week 4 and maturity evoked an initial corticospinal surface volley followed by a postsynaptic field response. Depth recordings from the superficial dorsal horn to the ventral white matter showed that local pre- and postsynaptic field potentials could be recorded over the full extent of the gray matter in 4- to 5-wk animals but were restricted to the intermediate zone in older animals and adults. Dorsoventral refinement of CS field potentials parallels anatomical refinement of individual CS axon terminals shown in our earlier studies. Our present findings indicate that the developing corticospinal system could influence the excitability of virtually the entire contralateral gray matter before cortical motor functions are expressed. Given the importance of activity-dependent axon terminal refinement, this capacity for activating spinal neurons during early postnatal life could play an important role in development of CS circuit connectivity.
Flash Photolysis Reveals a Diversity of Ionotropic Glutamate Receptors on the Mitral Cell Somatodendritic Membrane
Authors: Lowe Graeme
Published: May 2006

It is widely held that the soma and basal dendrites of olfactory bulb mitral cells receive exclusively inhibitory synaptic input from local interneurons. However, the mitral somatodendritic membrane exhibits immunoreactivity for a variety of glutamate receptors, and blocking GABA receptors unmasks mitral cell self-excitation. This excitation is proposed to be mediated either by diffuse spillover of the mitral cells' own released glutamate, or by punctate transmission from glutamate-releasing granule cells. This study examined the pharmacology and kinetics of glutamate sensitivity of mitral cells by flash photolysis of nitroindoline caged glutamates, which facilitate reliable activation of receptors in the synaptic cleft. Wide-field laser uncaging (3.5-ms flash) of approximately 0.5–1 mM glutamate onto the soma activated large currents with fast (3.4-ms rise, 7.5-ms decay) and slow (64-ms rise, >10-s decay) components. In 100 μM APV, slow currents were reduced to 53% of control (257-ms rise, 2-s decay), displayed outward rectification in 1.3 mM Mg2+, and blocked by 15 μM 5,7-dichlorokynurenate. Responses to ≲100 μM glutamate were fully antagonized by 100 μM APV, consistent with competitive inhibition at high-affinity NMDA receptors. An APV-resistant NMDA receptor was not observed, refuting the punctate transmission model. Fast currents were blocked by 10 μM NBQX, boosted 3.28-fold by 100 μM cyclothiazide, and resolved into AMPA (40%) and kainate (60%) receptor components by 100 μM SYM2206. The results suggest that self-excitation depends on AMPA, kainite, and conventional NMDA autoreceptors on the mitral cell.
Nondominant Arm Advantages in Load Compensation During Rapid Elbow Joint Movements
Authors: Bagesteiro Leia B. , Sainburg Robert L.
Published: May 2006

This study was designed to examine interlimb asymmetries in responding to unpredictable changes in inertial loads, which have implications for our understanding of the neural mechanisms underlying handedness. Subjects made repetitive single joint speed constrained 20° elbow flexion movements, while the arm was supported on a horizontal, frictionless, air-jet system. On random trials, a 2-kg mass was attached to the arm splint prior to the “go” signal. Subjects were not given explicit information about the mass prior to movement nor were they able to view their limb or the mass. Accordingly, muscle activity, recorded prior to peak tangential finger acceleration, was the same for loaded and baseline trials. After this point, substantial changes in muscle activity occurred. In both limbs, the load compensation response was associated with a reduction in extensor muscle activity, resulting in a prolonged flexion phase of motion. For the nondominant arm, this resulted in effective load compensation, such that no differences in final position accuracy occurred between loaded and baseline trials. However, the dominant arm response also included a considerable increase in flexor muscle activity. This substantially prolonged the flexor acceleration phase of motion, relative to that of the nondominant arm. As a result, the dominant arm overcompensated the effects of the load, producing a large and systematic overshoot of final position. These results indicate more effective load compensation responses for the nondominant arm; supporting a specialized role of the nondominant arm/hemisphere system in sensory feedback mediated error correction mechanisms. The results also suggest that specialization of the dominant arm system for controlling limb and task dynamics is specifically related to feedforward control mechanisms.
Representation of Cardinal Contour Overlaps Less With Representation of Nearby Angles in Cat Visual Cortex
Authors: Wang Gang , Ding Shan , Yunokuchi Kazutomo
Published: May 2006

Extensive attempts have been made to explain the neurobiological basis of the greater sensitivity of the visual system to vertically or horizontally oriented information than to information presented at oblique angles. However, investigators have largely ignored the overlap of the representation of a given angle with the representation of nearby angles. Recordings based on intrinsic optical signals were obtained in area 17 from 12 adult cats during the presentation of contours in various orientations. A method investigating both amplitude and statistical significance of changes was proposed to evaluate the orientation tuning properties for cell populations in the central area retinotopically corresponding to 0–15° of visual field. Cardinal orientations were found to activate significantly greater areas in the exposed cortical area than the areas activated by oblique orientations. Areas activated by cardinal or oblique contours and those separated from them by 10° were compared. A significantly lower degree of overlap was seen between areas activated by presentation of cardinal contours and areas activated by neighboring orientations compared with those for oblique orientations which overlapped more extensively with neighboring orientations. In addition, areas activated only by cardinal contours were significantly larger than areas activated only by oblique contours. These results demonstrated in cell population level that more cells prefer horizontal or vertical orientations, and these cells are tuned more sharply than oblique selective cells.
Dorsal and Ventral Distribution of Excitable and Synaptic Properties of Neurons of the Bed Nucleus of the Stria Terminalis
Authors: Egli Regula E. , Winder Danny G.
Published: May 2006

The bed nucleus of the stria terminalis (BNST) is a structure uniquely positioned to integrate stress information and regulate both stress and reward systems. Consistent with this arrangement, evidence suggests that the BNST, and in particular the noradrenergic input to this structure, is a key component of affective responses to drugs of abuse. We have utilized an in vitro slice preparation from adult mice to determine synaptic and membrane properties of these cells, focusing on the dorsal and ventral subdivisions of the anterolateral BNST (dBNST and vBNST) because of the differential noradrenergic input to these two regions. We find that while resting membrane potential and input resistance are comparable between these subdivisions, excitable properties, including a low-threshold spike (LTS) likely mediated by T-type calcium channels and an Ih-dependent potential, are differentially distributed. Inhibitory and excitatory postsynaptic potentials (IPSPs and EPSPs, respectively) are readily evoked in both dBNST and vBNST. The fast IPSP is predominantly GABAA-receptor mediated and is partially blocked by the AMPA/kainate-receptor antagonist CNQX. In the presence of the GABAA-receptor antagonist picrotoxin, cells in dBNST but not vBNST are more depolarized and have a higher input resistance, suggesting tonic GABAergic inhibition of these cells. The EPSPs elicited in BNST are monosynaptic, exhibit paired pulse facilitation, and contain both an AMPA- and an N-methyl-d-aspartate (NMDA) receptor-mediated component. These data support the hypothesis that neurons of the dorsal and ventral BNST differentially integrate synaptic input, which is likely of behavioral significance. The data also suggest mechanisms by which information may flow through stress and reward circuits.
Conditions for the Triggering of Spreading Depression Studied With Computer Simulations
Authors: Kager H. , Wadman W. J. , Somjen G. G.
Published: May 2006

In spite of five decades of study, the biophysics of spreading depression (SD) is incompletely understood. Earlier we have modeled seizures and SD, and we have shown that currents through ion channels normally present in neuron membranes can generate SD-like depolarization. In the present study, we define the conditions for triggering SD and the parameters that influence its course in a model of a hippocampal pyramidal cell with more complete representation of ions and channels than the previous version. “Leak” conductances for Na+, K+, and Cl− and an ion pump were present in the membrane of the entire cell; fast inactivating voltage dependent conductances for sodium and potassium in the soma; “persistent” conductances in soma and apical dendrite, and K+- and voltage-dependent N-methyl-d-aspartate (NMDA)-controlled conductance in the apical dendrite. The neuron was surrounded by restricted interstitial space and by a “glia-endothelium” system of extracellular ion regulation bounded by a membrane having leak conductances and an ion pump. Ion fluxes and concentration changes were continuously computed as well as osmotic cell volume changes. As long as reuptake into the neuron and “buffering” by glia kept pace with K+ released from the neuron, stimulating current applied to the soma evoked repetitive firing that stopped when stimulation ceased. When glial uptake was reduced, K+ released from neurons could accumulate in the interstitium and keep the neuron depolarized so that strong depolarizing pulses injected into the soma were followed either by afterdischarge or SD. SD-like depolarization was ignited when depolarization spreading into the apical dendrite, activated persistent Na+ current and NMDA-controlled current. With membrane parameters constant, varying the injected stimulating current influenced SD onset but neither the depolarization nor the increase in extracellular K+. Glial “leak” conductance influenced SD duration and SD ignition point. Varying maximal conductances (representing channel density) also influenced SD onset time but not the amplitude of the depolarization. Hypoxia was simulated by turning off the Na-K exchange pump, and this resulted in SD-like depolarization. The results confirm that, once ignited, SD runs an all-or-none trajectory, the level of depolarization is governed by feedback involving ion shifts and glutamate acting on ion channels and not by the number of channels open, and SD is ignited if the net persistent membrane current in the apical dendrites turns inward.
Temporal Coherence Sensitivity in Auditory Cortex
Authors: Barbour Dennis L. , Wang Xiaoqin
Published: May 2006

Natural sounds often contain energy over a broad spectral range and consequently overlap in frequency when they occur simultaneously; however, such sounds under normal circumstances can be distinguished perceptually (e.g., the cocktail party effect). Sound components arising from different sources have distinct (i.e., incoherent) modulations, and incoherence appears to be one important cue used by the auditory system to segregate sounds into separately perceived acoustic objects. Here we show that, in the primary auditory cortex of awake marmoset monkeys, many neurons responsive to amplitude- or frequency-modulated tones at a particular carrier frequency [the characteristic frequency (CF)] also demonstrate sensitivity to the relative modulation phase between two otherwise identically modulated tones: one at CF and one at a different carrier frequency. Changes in relative modulation phase reflect alterations in temporal coherence between the two tones, and the most common neuronal response was found to be a maximum of suppression for the coherent condition. Coherence sensitivity was generally found in a narrow frequency range in the inhibitory portions of the frequency response areas (FRA), indicating that only some off-CF neuronal inputs into these cortical neurons interact with on-CF inputs on the same time scales. Over the population of neurons studied, carrier frequencies showing coherence sensitivity were found to coincide with the carrier frequencies of inhibition, implying that inhibitory inputs create the effect. The lack of strong coherence-induced facilitation also supports this interpretation. Coherence sensitivity was found to be greatest for modulation frequencies of 16–128 Hz, which is higher than the phase-locking capability of most cortical neurons, implying that subcortical neurons could play a role in the phenomenon. Collectively, these results reveal that auditory cortical neurons receive some off-CF inputs temporally matched and some temporally unmatched to the on-CF input(s) and respond in a fashion that could be utilized by the auditory system to segregate natural sounds containing similar spectral components (such as vocalizations from multiple conspecifics) based on stimulus coherence.
Visual Tracking Neurons in Primate Area MST Are Activated by Smooth-Pursuit Eye Movements of an “Imaginary” Target
Authors: Ilg Uwe J. , Thier Peter
Published: May 2006

Because smooth-pursuit eye movements (SPEM) can be executed only in the presence of a moving target, it has been difficult to attribute the neuronal activity observed during the execution of these eye movements to either sensory processing or to motor preparation or execution. Previously, we showed that rhesus monkeys can be trained to perform SPEM directed toward an “imaginary” target defined by visual cues confined to the periphery of the visual field. The pursuit of an “imaginary” target provides the opportunity to elicit SPEM without stimulating visual receptive fields confined to the center of the visual field. Here, we report that a subset of neurons [85 “ imaginary” visual tracking (iVT)-neurons] in area MST of 3 rhesus monkeys were identically activated during pursuit of a conventional, foveal dot target and the “imaginary” target. Because iVT-neurons did not respond to the presentation of a moving “imaginary” target during fixation of a stationary dot, we are able to exclude that responses to pursuit of the “imaginary” target were artifacts of stimulation of the visual field periphery. Neurons recorded from the representation of the central parts of the visual field in neighboring area MT, usually vigorously discharging during pursuit of foveal targets, in no case responded to pursuit of the “imaginary” target. This dissociation between MT and MST neurons supports the view that pursuit responses of MT neurons are the result of target image motion, whereas those of iVT-neurons in area MST reflect an eye movement–related signal that is nonretinal in origin. iVT-neurons fell into two groups, depending on the properties of the eye movement–related signal. Whereas most of them (71%) encoded eye velocity, a minority showed responses determined by eye position, irrespective of whether eye position was changed by smooth pursuit or by saccades. Only the former group exhibited responses that led the eye movement, which is a prerequisite for a causal role in the generation of SPEM.
PACAP Is Present in the Olfactory System and Evokes Calcium Transients in Olfactory Receptor Neurons
Authors: Hegg Colleen C. , Au Edmund , Roskams A. Jane , Lucero Mary T.
Published: May 2006

Pituitary adenylate cyclase activating peptide (PACAP), a neuroregulatory peptide, is found in germinative regions of the CNS, including the olfactory bulb, throughout adulthood. We show that 1) PACAP immunoreactivity is also present in the neonatal mouse and adult mouse and rat olfactory epithelium, 2) PACAP expression pattern differs between neonatal and adult mice, and 3) PACAP is produced by olfactory ensheathing cells. PACAP may thus be a key factor in the uniquely supportive role of olfactory ensheathing cells in regeneration of neurons from olfactory epithelium and lesioned spinal cord. Using calcium imaging, we demonstrated physiological responses to PACAP in both neonatal and adult olfactory receptor neurons (ORNs). We propose that PACAP plays an important role in normal turnover of ORNs by providing neurotrophic support during development and regeneration and neuroprotective support of mature neurons.
Effects of Combined and Separate Removals of Rostral Dorsal Superior Temporal Sulcus Cortex and Perirhinal Cortex on Visual Recognition Memory in Rhesus Monkeys
Authors: Hadfield Wendy S. , Baxter Mark G. , Murray Elisabeth A.
Published: May 2006

The dorsal bank of the superior temporal sulcus (STSd) bears anatomical relations similar to those of perirhinal cortex, an area critical for visual recognition memory. To examine whether STSd makes a similar contribution to visual recognition memory, performance on visual delayed nonmatching-to-sample (DNMS) was assessed in rhesus monkeys with combined or separate ablations of the perirhinal cortex and STSd as well as in unoperated controls. Consistent with previous findings, ablations of perirhinal cortex produced deficits nearly as severe as that found after rhinal (i.e., entorhinal plus perirhinal) cortex lesions. However, combined lesions of perirhinal cortex and STSd produced a deficit no greater than that produced by perirhinal cortex ablation alone, and lesions of STSd alone were without effect on DNMS. We conclude that STSd is not critically involved in visual recognition memory.
Neural Activity in Monkey Dorsal and Ventral Cingulate Motor Areas: Comparison with the Supplementary Motor Area
Authors: Russo Gary S. , Backus Deborah A. , Ye Shuping , Crutcher Michael D.
Published: May 2006

The cingulate motor areas are a recently discovered group of discrete cortical regions located in the cingulate sulcus with direct connections to the primary motor cortex and spinal cord. Although much is known about their anatomical relationship with other motor areas, relatively little is known about their functional neurophysiology. We investigated neural mechanisms of motor processing in the dorsal and ventral cingulate motor areas (CMAd and CMAv) during two-dimensional visually guided arm movements. Single-neuron activity in CMAd and CMAv was recorded during an instructed delay task requiring combined elbow and shoulder movements. Neural activity associated with the onset of a visual cue (signal activity), delay (set activity), and motor response (movement activity) were assessed, and their onset time, duration, magnitude, and parameters of directional specificity were calculated. To determine how CMAd and CMAv compared with other premotor areas, we also analyzed the activity of neurons in the supplementary motor area (SMA) during the same task in the same monkeys. Comparison of CMAd, CMAv, and SMA revealed remarkably similar response properties. All three areas contained signal, set, and movement activity in similar proportions and in all possible combinations within single neurons. The average onset time of signal and set activity and the duration of signal activity were not significantly different across areas. The directional tuning of activities in all three areas were uniformly distributed and highly correlated within the same neuron. There were, however, some notable differences in movement activity between motor areas. Neurons with only movement activity were more numerous in CMAd and CMAv, whereas neurons with both set and movement activity were more prevalent in SMA. Furthermore, movement activity in SMA began earlier and had a shorter duration than movement activity in CMAd and CMAv, although there was substantial overlap in their distributions. These results indicate that CMAd and CMAv participate in the visual guidance of limb movements using similar neurophysiological mechanisms as SMA. The earlier average onset and shorter duration of movement activity in SMA suggest a more prominent role for this area in movement initiation, whereas the later onset and longer duration of movement activity in CMAd and CMAv suggest a more influential role in movement execution. Notwithstanding these differences, however, the remarkable similarities in response types and their combinatorial organization within single neurons across all cortical areas attests to the parallel organization and distributed nature of information processing in these three motor areas.
ERK Integrates PKA and PKC Signaling in Superficial Dorsal Horn Neurons. I. Modulation of A-Type K+Currents
Authors: Hu Hui-Juan , Glauner Kathi S. , Gereau Robert W.
Published: May 2006

The transient outward potassium currents (also known as A-type currents or IA) are important determinants of neuronal excitability. In the brain, IAis modulated by protein kinase C (PKC), protein kinase A (PKA), and extracellular signal-related kinase (ERK), three kinases that have been shown to be critical modulators of nociception. We wanted to determine the effects of these kinases on IAin superficial dorsal horn neurons. Using whole cell recordings from cultured mouse spinal cord superficial dorsal horn neurons, we found that PKC and PKA both inhibit IAin these cells, and that PKC has a tonic inhibitory action on IA. Further, we provide evidence supporting the hypothesis that PKC and PKA do not modulate IAdirectly, but rather act as upstream activators of ERKs, which modulate IA. These results suggest that ERKs serve as signal integrators in modulation of IAin dorsal horn neurons and that modulation of A-type potassium currents may underlie aspects of central sensitization mediated by PKC, PKA, and ERKs.
ERK Integrates PKA and PKC Signaling in Superficial Dorsal Horn Neurons. II. Modulation of Neuronal Excitability
Authors: Hu Hui-Juan , Gereau Robert W.
Published: May 2006

Protein kinases belonging to the protein kinase A (PKA), protein kinase C (PKC), and extracellular signal-related kinase (ERK) families have been identified as key players in modulating nociception at the level of the spinal cord dorsal horn, yet little is known about the effects of these kinases on membrane properties of the dorsal horn neurons. PKA, PKC, and ERK exert inhibitory effects on transient potassium currents (A-type currents or IA) in mouse superficial dorsal horn neurons ( Hu et al. 2003 ). Here we aimed to determine the effects of these kinases on action potential firing and membrane properties of these neurons to evaluate the impact of the modulation of IA (and other conductances) in these neurons. We found that activating PKC and PKA has dramatic effects on action potential firing, reflecting an increase in the excitability of superficial dorsal horn neurons. In addition, we found that inhibitors of both PKC and ERK signaling decrease the excitability of dorsal horn neurons, suggesting that these kinases exert a tonic excitation of these cells. Consistent with our findings that these kinases inhibit A-type currents, we found that PKA, PKC, and ERK act to shorten the first-spike latency after depolarization induced by current injection. In addition, activation of these kinases increases spike frequency and action potential amplitude of dorsal horn neurons. Interestingly, we found that the effects of PKA and PKC activators are blocked by inhibitors of ERK signaling, suggesting that PKA and PKC may exert their actions by activation of ERKs.
Cholinergic Modulation of Purinergic and GABAergic Co-Transmission at In Vitro Hypothalamic Synapses
Authors: Jo Young-Hwan , Role Lorna W.
Published: May 2006

The lateral hypothalamus (LH) is an important center for the integration of autonomic and limbic information and is implicated in the modulation of visceral motor and sensory pathways, including those underlying feeding and arousal behaviors. LH neurons in vitro release both ATP and GABA. The control of ATP and GABA co-transmission in LH may underlie the participation of LH in basic aspects of arousal and reinforcement. LH neurons receive cholinergic input from the pedunculopontine and laterodorsal tegmental nuclei as well as from cholinergic interneurons within the LH per se. This study presents evidence for nicotinic acetylcholine receptor (nAChR)-mediated enhancement of GABAergic, but not of purinergic, transmission despite the co-transmission of ATP and GABA at LH synapses in vitro. Facilitation of GABAergic transmission by nicotine is inhibited by antagonists of (αβ)*-containing nAChRs, but is unaffected by an α7-selective antagonist, consistent with a nAChR-mediated enhancement of GABA release mediated by non-α7-containing nAChRs. Activation of muscarinic ACh receptors enhances the release of ATP while concomitantly depressing GABAergic transmission. The independent modulation of ATP/GABAergic transmission may provide a new level of synaptic flexibility in which individual neurons utilize more than one neurotransmitter but retain independent control over their synaptic activity.
Neocortical Very Fast Oscillations (Ripples, 80–200 Hz) During Seizures: Intracellular Correlates
Authors: Grenier François , Timofeev Igor , Steriade Mircea
Published: May 2006

Multi-site field potential and intracellular recordings from various neocortical areas were used to study very fast oscillations or ripples (80–200 Hz) during electrographic seizures in cats under ketamine-xylazine anesthesia. The animals displayed spontaneously occurring and electrically induced seizures comprising spike-wave complexes (2–3 Hz) and fast runs (10–20 Hz). Neocortical ripples had much higher amplitudes during seizures than during the slow oscillation preceding the onset of seizures. A series of experimental data from the present study supports the hypothesis that ripples are implicated in seizure initiation. Ripples were particularly strong at the onset of seizures and halothane, which antagonizes the occurrence of ripples, also blocked seizures. The firing of electrophysiologically defined cellular types was phase-locked with ripples in simultaneously recorded field potentials. This indicates that ripples during paroxysmal events are associated with a coordination of firing in a majority of neocortical neurons. This was confirmed with dual intracellular recordings. Based on the amplitude that neocortical ripples reach during paroxysmal events, we propose a mechanism by which neocortical ripples during normal network activity could actively participate in the initiation of seizures on reaching a certain threshold amplitude. This mechanism involves a vicious feedback loop in which very fast oscillations in field potentials are a reflection of synchronous action potentials, and in turn these oscillations help generate and synchronize action potentials in adjacent neurons through electrical interactions.
Pursuit Subregion of the Frontal Eye Field Projects to the Caudate Nucleus in Monkeys
Authors: Cui Dong-Mei , Yan Yi-Jun , Lynch James C.
Published: May 2006

It has been well established by recording, inactivation, and neuroanatomical studies that the caudate nucleus is important for the control of saccadic eye movements. However, until now, there has been little evidence that the caudate nucleus plays a role in smooth pursuit eye movements. In the present study, we physiologically identified the smooth pursuit subregion of the frontal eye field (FEFsem) and the saccadic subregion of the frontal eye field (FEFsac) in four Cebus monkeys. Anterogradely transported tracers (biotinylated dextran amines and wheat germ aglutinin conjugated to horseradish peroxidase) were then used to determine the efferent connections of the FEFsem to the caudate nucleus and to compare those connections with projections arising in the FEFsac. We observed dense projections from the FEFsem to the head and body of the caudate. The FEFsem and FEFsac terminal fields were of approximately equal density and total area. The region of FEFsem-labeled axon terminals overlapped only slightly with the region of FEFsac-labeled terminals. These results suggest that the caudate nucleus may play an important role in the control of smooth pursuit eye movements via feedback loops involving the basal ganglia and thalamus. Our results further suggest that the basal ganglia circuitry concerned with controlling visual pursuit is physically segregated from that concerned with controlling saccadic eye movements.
Vestibular Convergence Patterns in Vestibular Nuclei Neurons of Alert Primates
Authors: Dickman J. David , Angelaki Dora E.
Published: May 2006

Sensory signal convergence is a fundamental and important aspect of brain function. Such convergence may often involve complex multidimensional interactions as those proposed for the processing of otolith and semicircular canal (SCC) information for the detection of translational head movements and the effective discrimination from physically congruent gravity signals. In the present study, we have examined the responses of primate rostral vestibular nuclei (VN) neurons that do not exhibit any eye movement-related activity using 0.5-Hz translational and three-dimensional (3D) rotational motion. Three distinct neural populations were identified. Approximately one-fourth of the cells exclusively encoded rotational movements (canal-only neurons) and were unresponsive to translation. The canal-only central neurons encoded head rotation in SCC coordinates, exhibited little orthogonal canal convergence, and were characterized with significantly higher sensitivities to rotation as compared to primary SCC afferents. Another fourth of the neurons modulated their firing rates during translation (otolith-only cells). During rotations, these neurons only responded when the axis of rotation was earth-horizontal and the head was changing orientation relative to gravity. The remaining one-half of VN neurons were sensitive to both rotations and translations (otolith + canal neurons). Unlike primary otolith afferents, however, central neurons often exhibited significant spatiotemporal (noncosine) tuning properties and a wide variety of response dynamics to translation. To characterize the pattern of SCC inputs to otolith + canal neurons, their rotational maximum sensitivity vectors were computed using exclusively responses during earth-vertical axis rotations (EVA). Maximum sensitivity vectors were distributed throughout the 3D space, suggesting strong convergence from multiple SCCs. These neurons were also tested with earth-horizontal axis rotations (EHA), which would activate both vertical canals and otolith organs. However, the recorded responses could not be predicted from a linear combination of EVA rotational and translational responses. In contrast, one-third of the neurons responded similarly during EVA and EHA rotations, although a significant response modulation was present during translation. Thus this subpopulation of otolith + canal cells, which included neurons with either high- or low-pass dynamics to translation, appear to selectively ignore the component of otolith-selective activation that is due to changes in the orientation of the head relative to gravity. Thus contrary to primary otolith afferents and otolith-only central neurons that respond equivalently to tilts relative to gravity and translational movements, approximately one-third of the otolith + canal cells seem to encode a true estimate of the translational component of the imposed passive head and body movement.
Comparison of the Morphological and Electrotonic Properties of Renshaw Cells, Ia Inhibitory Interneurons, and Motoneurons in the Cat
Authors: Bui T. V. , Cushing S. , Dewey D. , Fyffe R. E. , Rose P. K.
Published: May 2006

The morphological and electrotonic properties of 4 motoneurons, 8 Ia inhibitory interneurons, and 4 Renshaw cells were compared. The morphological analysis, based on 3-D reconstructions of the cells, revealed that dendrites of motoneurons are longer and more extensively branched. Renshaw cells have dendrites that are shorter and simpler in structure. Dendrites of Ia inhibitory interneurons could be as long as those of motoneurons but the branching structure resembled that of Renshaw cells. Compartmental models were used to determine the electrotonic properties of the paths from each dendritic terminal to the soma. The attenuations of steady-state voltage changes in motoneurons were 3 and 7 times larger than in Ia inhibitory interneurons and Renshaw cells, respectively. The same relative order was observed for current attenuation and electrotonic length. The dendritic input resistances in Renshaw cells were 2 and 4 times larger than in Ia inhibitory interneurons and motoneurons, respectively. The difference in these electrotonic properties increased during higher synaptic activity as modeled by a decrease of Rm. The peak amplitudes of voltage transients at sites of brief, synaptic-like changes in conductance were highly dependent on cell class and were largest in Renshaw cells and smallest in motoneurons. In combination with class-specific differences in the attenuation of transient voltage signals, this led to large differences in the peak amplitudes of somatic voltage transients. Differences in the rise times and half-widths of the voltage transients were observed as well. Thus, based on passive properties, each cell class has a unique set of input/output properties.
Role of the Electrogenic Na/K Pump in Disinhibition-Induced Bursting in Cultured Spinal Networks
Authors: Darbon P. , Tscherter A. , Yvon C. , Streit J.
Published: May 2006

Disinhibition-induced bursting activity in cultures of fetal rat spinal cord is mainly controlled by intrinsic spiking with subsequent recurrent excitation of the network through glutamate synaptic transmission, and by autoregulation of neuronal excitability. Here we investigated the contribution of the electrogenic Na/K pump to the autoregulation of excitability using extracellular recordings by multielectrode arrays (MEAs) and intracellular whole cell recordings from spinal interneurons. The blockade of the electrogenic Na/K pump by strophanthidin led to an immediate and transient increase in the burst rate together with an increase in the asynchronous background activity. Later, the burst rate decreased to initial values and the bursts became shorter and smaller. In single neurons, we observed an immediate depolarization of the membrane during the interburst intervals concomitant with the rise in burst rate. This depolarization was more pronounced during disinhibition than during control, suggesting that the pump was more active. Later a decrease in burst rate was observed and, in some neurons, a complete cessation of firing. Most of the effects of strophanthidin could be reproduced by high K+-induced depolarization. During prolonged current injections, spinal interneurons exhibited spike frequency adaptation, which remained unaffected by strophanthidin. These results suggest that the electrogenic Na/K pump is responsible for the hyperpolarization and thus for the changes in excitability during the interburst intervals, although not for the spike frequency adaptation during the bursts.
The Accessory Optic System Contributes to the Spatio-Temporal Tuning of Motion-Sensitive Pretectal Neurons
Authors: Crowder Nathan A. , Lehmann Hugo , Parent Marise B. , Wylie Douglas R.W.
Published: May 2006

The nucleus of the basal optic root (nBOR) of the accessory optic system (AOS) and the pretectal nucleus lentiformis mesencephali (LM) are involved in the analysis of optic flow that results from self-motion and are important for oculomotor control. These neurons have large receptive fields and exhibit direction selectivity to large moving stimuli. In response to drifting sine wave gratings, LM and nBOR neurons are tuned to either low spatial/high temporal frequencies (SF, TF) or high SF/low TF stimuli. Given that velocity = TF/SF, these are referred to as “fast” and “slow” neurons, respectively. There is a heavy projection from the AOS to the pretectum, although its function is unknown. We recorded the directional and spatio-temporal tuning of LM units in pigeons before and after nBOR was inactivated by tetrodotoxin injection. After nBOR inactivation, changes in direction preference were observed for only one of 18 LM units. In contrast, the spatio-temporal tuning of LM units was dramatically altered by nBOR inactivation. Two major effects were observed. First, in response to motion in the preferred direction, most (82%) neurons showed a substantially reduced (μ = –67%) excitation to low SF/high TF gratings. Second, in response to motion in the anti-preferred direction, most (63%) neurons showed a dramatically reduced (μ = –78%) inhibition to high SF/low TF gratings. Thus the projection from the nBOR contributes to the spatio-temporal tuning rather than the directional tuning of LM neurons. We propose a descriptive model whereby LM receives inhibitory and excitatory input from “slow” and “fast” nBOR neurons, respectively.