bluuebunny/crossref_metadata_2025 huggingface dataset:
The NMDA-to-AMPA Ratio at Synapses Onto Layer 2/3 Pyramidal Neurons Is Conserved Across Prefrontal and Visual Cortices
Authors: Myme Chaelon I. O. , Sugino Ken , Turrigiano Gina G. , Nelson Sacha B.
Published: May 2006

To better understand regulation of N-methyl-d-aspartate (NMDA) and α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor complements across the cortex, and to investigate NMDA receptor (NMDAR)-based models of persistent activity, we compared NMDA/AMPA ratios in prefrontal (PFC) and visual cortex (VC) in rat. Whole cell voltage-clamp responses were recorded in brain slices from layer 2/3 pyramidal cells of the medial PFC and VC of rats aged p16–p21. Mixed miniature excitatory postsynaptic currents (mEPSCs) having AMPA receptor (AMPAR)- and NMDAR-mediated components were isolated in nominally 0 Mg2+ACSF. Averaged mEPSCs were well-fit by double exponentials. No significant differences in the NMDA/AMPA ratio (PFC: 27 ± 1%; VC: 28 ± 3%), peak mEPSC amplitude (PFC: 19.1 ± 1 pA; VC: 17.5 ± 0.7 pA), NMDAR decay kinetics (PFC: 69 ± 8 ms; VC: 67 ± 6 ms), or degree of correlation between NMDAR- and AMPAR-mediated mEPSC components were found between the areas (PFC: n = 27; VC: n = 28). Recordings from older rats (p26–29) also showed no differences. EPSCs were evoked extracellularly in 2 mM Mg2+at depolarized potentials; although the average NMDA/AMPA ratio was larger than that observed for mEPSCs, the ratio was similar in the two regions. In nominally 0 Mg2+and in the presence of CNQX, spontaneous activation of NMDAR increased recording noise and produced a small tonic depolarization which was similar in both areas. We conclude that this basic property of excitatory transmission is conserved across PFC and VC synapses and is therefore unlikely to contribute to differences in firing patterns observed in vivo in the two regions.
Macaque Frontal Eye Field Input to Saccade-Related Neurons in the Superior Colliculus
Authors: Helminski Janet O. , Segraves Mark A.
Published: May 2006

Extracellular recordings were made simultaneously in the frontal eye field and superior colliculus in awake, behaving rhesus monkeys. Frontal eye field microstimulation was used to orthodromically activate the superior colliculus both to locate the depth of the strongest frontal eye field input to the superior colliculus and to identify superior colliculus neurons receiving direct frontal eye field input. The activity of orthodromically driven colliculus neurons was characterized during visuomotor tasks. The purpose of this study was to identify the types of superior colliculus neurons that receive excitatory frontal eye field input. We found that microstimulation of the frontal eye field did not activate the superficial layers of the superior colliculus but did activate the deeper layers. This pattern of activation coincided with the prevalence of visual versus saccade-related activity in the superficial and deep layers. A total of 83 orthodromically driven superior colliculus neurons were identified. Of these neurons, 93% ( n = 77) exhibited a burst of activity associated with the onset of the saccade, and 25% ( n = 21) exhibited prelude/build-up activity prior to the onset of a saccade. In addition, it was common to see some activity synchronized with the onset of a visual target (30%, n = 25). In single neurons, these activity profiles could be observed alone or in combination. Superior colliculus neurons that were exclusively visual, however, were not excited by frontal eye field stimulation. We compared the activity of superior colliculus neurons that received frontal eye field input to descriptions of saccade-related neurons made in earlier reports and found that the distribution of neuron types in the orthodromically driven population was similar to the distribution within the overall population. This suggests that the frontal eye field does not selectively influence a specific class of collicular neurons, but, instead has a direct influence on all preparatory, and saccade-related activity within the deep layers of the superior colliculus.
Reduced Synaptic Plasticity in the Lateral Perforant Path Input to the Dentate Gyrus of Aged C57BL/6 Mice
Authors: Froc David J. , Eadie Brennan , Li Amanda M. , Wodtke Karl , Tse Maric , Christie Brian R.
Published: May 2006

Hippocampal slices obtained from C57BL/6 mice (3–25 mo) were used to investigate the effects of aging on excitatory postsynaptic potentials (EPSPs) elicited in dentate gyrus with lateral perforant path stimulation. The maximal amplitude of the EPSP, as well as the degree of paired-pulse facilitation, was significantly reduced in animals aged 12 mo or more compared with younger animals (<12 mo). Although all animals showed equivalent short-term potentiation (STP) in response to high-frequency stimulation, this did not translate into a long-lasting increase in synaptic efficacy in the older animals. A significant degree of long-term potentiation (LTP) of synaptic efficacy was only observed in animals <12 mo of age when measured 30 min after induction. Blocking GABAA-mediated inhibition significantly enhanced STP in younger and older animals; however, a significant degree of LTP was again only observed in slices taken from younger animals. These data indicate that the lateral perforant path input to the dentate gyrus is altered by the aging process, and that this results in a reduction in the capacity of this input to exhibit long-lasting synaptic plasticity.
Brain Responses Associated With the Valsalva Maneuver Revealed by Functional Magnetic Resonance Imaging
Authors: Henderson Luke A. , Macey Paul M. , Macey Katherine E. , Frysinger Robert C. , Woo Mary A. , Harper Rebecca K. , Alger Jeffry R. , Yan-Go Frisca L. , Harper Ronald M.
Published: May 2006

The Valsalva maneuver, a test frequently used to evaluate autonomic function, recruits discrete neural sites. The time courses of neural recruitment relative to accompanying cardiovascular and breathing patterns are unknown. We examined functional magnetic resonance imaging signal changes within the brain to repeated Valsalva maneuvers and correlated these changes with physiological trends. In 12 healthy subjects (age, 30–58 yr), a series of 25 volumes (20 gradient echo echo-planar image slices per volume) was collected using a 1.5-Tesla scanner during a 60-s baseline and 90-s challenge period consisting of three Valsalva maneuvers. Regions of interest were examined for signal intensity changes over baseline and challenge conditions in cardiorespiratory-related regions. In addition, whole brain correlations between signal intensity and heart rate and airway load pressure were performed on a voxel-by-voxel basis. Significant signal changes, correlated with the time course of load pressure and heart rate, emerged within multiple areas, including the amygdala and hippocampus, insular and lateral frontal cortices, dorsal pons, dorsal medulla, lentiform nucleus, and fastigial and dentate nuclei of the cerebellum. Signal intensities peaked early in the Valsalva maneuver within the hippocampus and amygdala, later within the dorsal medulla, pons and midbrain, and deep cerebellar nuclei, and last within the lentiform nuclei and the lateral prefrontal cortex. The ventral pontine signals increased during the challenge, but not in a fashion correlated to load pressure or heart rate. Sites showing little or no correlation included the vermis and medial prefrontal cortex. These data suggest an initiating component arising in rostral brain areas, a later contribution from cerebellar nuclei, basal ganglia, and lateral prefrontal cortex, and a role for the ventral pons in mediating longer term processes.
Massively Parallel Recording of Unit and Local Field Potentials With Silicon-Based Electrodes
Authors: Csicsvari Jozsef , Henze Darrell A. , Jamieson Brian , Harris Kenneth D. , Sirota Anton , Barthó Péter , Wise Kensall D. , Buzsáki György
Published: May 2006

Parallel recording of neuronal activity in the behaving animal is a prerequisite for our understanding of neuronal representation and storage of information. Here we describe the development of micro-machined silicon microelectrode arrays for unit and local field recordings. The two-dimensional probes with 96 or 64 recording sites provided high-density recording of unit and field activity with minimal tissue displacement or damage. The on-chip active circuit eliminated movement and other artifacts and greatly reduced the weight of the headgear. The precise geometry of the recording tips allowed for the estimation of the spatial location of the recorded neurons and for high-resolution estimation of extracellular current source density. Action potentials could be simultaneously recorded from the soma and dendrites of the same neurons. Silicon technology is a promising approach for high-density, high-resolution sampling of neuronal activity in both basic research and prosthetic devices.
Activation of NMDA Receptors in Rat Dentate Gyrus Granule Cells by Spontaneous and Evoked Transmitter Release
Authors: Dalby Nils Ole , Mody Istvan
Published: May 2006

Activation of N-methyl-d-aspartate (NMDA) receptors by synaptically released glutamate in the nervous system is usually studied using evoked events mediated by a complex mixture of AMPA, kainate, and NMDA receptors. Here we have characterized pharmacologically isolated spontaneous NMDA receptor-mediated synaptic events and compared them to stimulus evoked excitatory postsynaptic currents (EPSCs) in the same cell to distinguish between various modes of activation of NMDA receptors. Spontaneous NMDA receptor-mediated EPSCs recorded at 34°C in dentate gyrus granule cells (DGGC) have a frequency of 2.5 ± 0.3 Hz and an average peak amplitude of 13.2 ± 0.8 pA, a 10–90% rise time of 5.4 ± 0.3 ms, and a decay time constant of 42.1 ± 2.1 ms. The single-channel conductance estimated by nonstationary fluctuation analysis was 60 ± 5 pS. The amplitudes (46.5 ± 6.4 pA) and 10–90% rise times (18 ± 2.3 ms) of EPSCs evoked from the entorhinal cortex/subiculum border are significantly larger than the same parameters for spontaneous events (paired t-test, P < 0.05, n = 17). Perfusion of 50 μM d(–)-2-amino-5-phosphonopentanoic acid blocked all spontaneous activity and caused a significant baseline current shift of 18.8 ± 3.0 pA, thus identifying a tonic conductance mediated by NMDA receptors. The NR2B antagonist ifenprodil (10 μM) significantly reduced the frequency of spontaneous events but had no effect on their kinetics or on the baseline current or variance. At the same time, the peak current and charge of stimulus-evoked events were significantly diminished by ifenprodil. Thus spontaneous NMDA receptor-mediated events in DGGC are predominantly mediated by NR2A or possibly NR2A/NR2B receptors while the activation of NR2B receptors reduces the excitability of entorhinal afferents either directly or through an effect on the entorhinal cells.
Rapid, Experience-Induced Enhancement in Odorant Discrimination by Anterior Piriform Cortex Neurons
Authors: Wilson Donald A.
Published: May 2006

Current views of odorant discrimination by the mammalian olfactory system suggest that the piriform cortex serves as a site of odor object synthesis. Given the enormous number of odorant feature combinations possible in nature, however, it seems unlikely that cortical synthetic receptive fields (RFs) are innate but rather require experience for their formation. The present experiment addressed two issues. First, we made a direct comparison of mitral/tufted cell and anterior piriform cortex (aPCX) neuron abilities to discriminate odorant mixtures from their components to further test whether aPCX neurons can treat collections of features different from the features themselves (synthetic coding). Second, we attempted to determine the minimum duration of experience necessary for formation of cortical synthetic RFs. Single-unit recordings were made from mitral/tufted cells and aPCX layer II/III neurons in urethan-anesthetized rats. Cross-habituation between novel binary mixtures and their novel components was used to determine odor discrimination abilities. The results suggest that after ≥50 s of experience with a binary mixture, aPCX neurons can discriminate the mixture from its components, whereas mitral/tufted cells cannot. However, when limited to 10 s of experience with the mixture, aPCX neurons appear similar to mitral/tufted cells and do not discriminate mixtures from components. These results suggest experience-dependent synthetic processing in aPCX and suggest an important role for perceptual learning in normal odor discrimination.
Correlated Discharges Among Putative Pyramidal Neurons and Interneurons in the Primate Prefrontal Cortex
Authors: Constantinidis Christos , Goldman-Rakic Patricia S.
Published: May 2006

Neurophysiological recordings have revealed that the discharges of nearby cortical cells are positively correlated in time scales that range from millisecond synchronization of action potentials to much slower firing rate co-variations, evident in rates averaged over hundreds of milliseconds. The presence of correlated firing can offer insights into the patterns of connectivity between neurons; however, few models of population coding have taken account of the neuronal diversity present in cerebral cortex, notably a distinction between inhibitory and excitatory cells. We addressed this question in the monkey dorsolateral prefrontal cortex by recording neuronal activity from multiple micro-electrodes, typically spaced 0.2–0.3 mm apart. Putative excitatory and inhibitory neurons were distinguished based on their action potential waveform and baseline discharge rate. We tested each pair of simultaneously recorded neurons for presence of significant cross-correlation peaks and measured the correlation of their averaged firing rates in successive trials. When observed, cross-correlation peaks were centered at time 0, indicating synchronous firing consistent with two neurons receiving common input. Discharges in pairs of putative inhibitory interneurons were found to be significantly more strongly correlated than in pairs of putative excitatory cells. The degree of correlated firing was also higher for neurons with similar spatial receptive fields and neurons active in the same epochs of the behavioral task. These factors were important in predicting the strength of both short time scale (<5 ms) correlations and of trial-to-trial discharge rate covariations. Correlated firing was only marginally accounted for by motor and behavioral variations between trials. Our findings suggest that nearby inhibitory neurons are more tightly synchronized than excitatory ones and account for much of the correlated discharges commonly observed in undifferentiated cortical networks. In contrast, the discharge of pyramidal neurons, the sole projection cells of the cerebral cortex, appears largely independent, suggesting that correlated firing may be a property confined within local circuits and only to a lesser degree propagated to distant cortical areas and modules.
Counteractive Relationship Between the Interaction Torque and Muscle Torque at the Wrist Is Predestined in Ball-Throwing
Authors: Hirashima Masaya , Ohgane Kunishige , Kudo Kazutoshi , Hase Kazunori , Ohtsuki Tatsuyuki
Published: May 2006

Many investigators have demonstrated that in swing motions such as ball-throwing, the motion of the proximal joint (shoulder) produced assistive interaction torque for the distal joint (elbow). In line with these studies, the shoulder and elbow motions would be expected to produce the assistive interaction torque for the wrist joint as well. However, we recently showed that the interaction torque at the wrist was always counteractive to the wrist muscle torque during ball-throwing. The purpose of this study is to clarify, by means of computer simulation, whether the counteractive relationship at the wrist during ball-throwing is caused by the neural contribution or the musculoskeletal mechanical properties of the human arm. First, we simulated the throwing motions of the normal forearm-hand model by systematically changing the proximal-to-distal delay of muscle activities and could line up two candidates for the determinant of the counteractive relationship: the rest angle (neutral angle) of the wrist and the length and mass of the hand. Second, we simulated the throwing motions of the virtual forearm-hand models, showing that only nonrealistic elongation of these two parameters produced the assistive relationship between the interaction torque and muscle torque. These results suggested that the mechanical properties of the human wrist are the main determinant of the counteractive relationship, which is advantageous for keeping the state of the wrist joint stable in multi-joint upper-limb movements and would lead to avoidance of excessive wrist extension or flexion and simplification of extrinsic finger control.
Temporal Components of the Motor Patterns Expressed by the Human Spinal Cord Reflect Foot Kinematics
Authors: Ivanenko Yuri P. , Grasso Renato , Zago Myrka , Molinari, Marco , Scivoletto Giorgio , Castellano Vincenzo , Macellari Velio , Lacquaniti, Francesco
Published: May 2006

What are the building blocks with which the human spinal cord constructs the motor patterns of locomotion? In principle, they could correspond to each individual activity pattern in dozens of different muscles. Alternatively, there could exist a small set of constituent temporal components that are common to all activation patterns and reflect global kinematic goals. To address this issue, we studied patients with spinal injury trained to step on a treadmill with body weight support. Patients learned to produce foot kinematics similar to that of healthy subjects but with activity patterns of individual muscles generally different from the control group. Hidden in the muscle patterns, we found a basic set of five temporal components, whose flexible combination accounted for the wide range of muscle patterns recorded in both controls and patients. Furthermore, two of the components were systematically related to foot kinematics across different stepping speeds and loading conditions. We suggest that the components are related to control signals output by spinal pattern generators, normally under the influence of descending and afferent inputs.
Conditioned H-Reflex Increase Persists After Transection of the Main Corticospinal Tract in Rats
Authors: Chen Xiang Yang , Chen Lu , Wolpaw Jonathan R.
Published: May 2006

The brain shapes spinal cord function throughout life. Operant conditioning of the H-reflex, the electrical analog of the spinal stretch reflex (SSR), is a relatively simple model for exploring the spinal cord plasticity underlying this functional change and may provide a new method for modifying spinal cord reflexes after spinal cord injury. In response to an operant conditioning protocol, rats can gradually increase (i.e., up-training mode) or decrease (i.e., down-training mode) the soleus H-reflex. This study explored the effects of midthoracic transection of the ipsilateral lateral column (LC) (rubrospinal, vestibulospinal, and reticulospinal tracts), the dorsal column corticospinal tract (CST), or the dorsal column ascending tract (DA) on maintenance of an H-reflex increase that has already occurred. Rats were implanted with EMG electrodes in the right soleus muscle and a nerve-stimulating cuff on the right posterior tibial nerve. After initial (i.e., control) H-reflex size was determined, the rats were exposed for 50 days to the up-training mode, in which reward was given when the H-reflex was above a criterion value. H-reflex size gradually rose to 168 ± 12% (mean ± SE) of its initial value. Each rat then received an LC, CST, or DA transection and continued under the up-training mode for 50 more days. None of the transections abolished the H-reflex increase. H-reflex size increased further to 197 ± 19% of its initial value and did not differ significantly among LC, CST, and DA rats ( P > 0.78 by ANOVA). Although earlier studies show that the main CST is needed for acquisition of H-reflex up-training and down-training and for maintenance of down-training, this study shows that it is not needed for maintenance of up-training. It adds to the evidence that H-reflex conditioning changes the spinal cord and that the spinal cord plasticity associated with up-training is different from that associated with down-training.
Voltage-Gated Na+ Channels Enhance the Temporal Filtering Properties of Electrosensory Neurons in the Torus
Authors: Fortune Eric S. , Rose Gary J.
Published: May 2006

Regenerative processes enhance postsynaptic potential (PSP) amplitude and behaviorally relevant temporal filtering in more than one-third of electrosensory neurons in the torus semicircularis of Eigenmannia. Data from in vivo current-clamp intracellular recordings indicate that these “regenerative PSPs” can be divided in two groups based on their half-amplitude durations: constant duration (CD) and variable duration (VD) PSPs. CD PSPs have half-amplitude durations of between 20 and 60 ms that do not vary in relation to stimulus periodicity. In contrast, the half-amplitude durations of VD PSPs vary in relation to stimulus periodicity and range from approximately 10 to 500 ms. Injection of 0.1 nA sinusoidal current through the recording electrode demonstrated that CD PSPs and not VD PSPs can be elicited by voltage fluctuations alone. In addition, CD PSPs were blocked by intracellular application of either QX-314 or QX-222, whereas VD PSPs were not. These in vivo data suggest, therefore, that CD PSPs are mediated by voltage-dependent Na+ conductances.
Spinal Neuronal Responses to Urinary Bladder Stimulation in Rats With Corticosterone or Aldosterone Onto the Amygdala
Authors: Qin Chao , Greenwood-Van Meerveld Beverley , Foreman Robert D.
Published: May 2006

Elevating glucocorticoids in the amygdala produces colorectal hypersensitivity through activation of lumbosacral spinal neurons. The aim of this study was to determine if descending modulation from the amygdala affects spinal processing of input from urinary bladder afferents. Fischer-344 rats received cholesterol (inactive control)-, corticosterone-, or aldosterone-containing micropellets placed stereotaxically on the dorsal margin of the left and right amygdala ( n = 10 for each group). Seven days after amygdaloid implantation, extracellular potentials of single L6–S1 spinal neurons were examined for the responses to graded (0.5–2.0 ml, 20 s) urinary bladder distension (UBD). Spontaneous activity of neurons with excitatory responses to UBD in aldosterone-implanted rats [11.0 ± 1.7 (SE) imp/s], but not in corticosterone-implanted rats, was higher than in the cholesterol-implanted group (6.6 ± 1.1 imp/s, P < 0.05). Noxious UBD (1.5 ml) produced a greater excitatory response (21.6 ± 2.6 imp/s) in aldosterone-implanted rats compared with cholesterol- or corticosterone-implanted rats (15.1 ± 1.5 and 13.6 ± 1.4 imp/s; P < 0.05). In contrast, the duration of excitatory responses to UBD in corticosterone-implanted rats (38.5 ± 3.4 imp/s) was significantly longer than those in the aldosterone or control groups (26.8 ± 1.8 and 24.7 ± 1.5 imp/s). Neurons with low thresholds for excitatory responses to UBD were seen more frequently in aldosterone-implanted rats than in corticosterone or cholesterol treated rats (74 vs. 44% and 39%, P < 0.05). No difference in somatic field properties of spinal neurons responsive or nonresponsive to UBD was found among the three groups. These findings suggest that both mineralocorticoid- and glucocorticoid-mediated mechanisms in the amygdala are involved in descending modulation to lumbosacral spinal neurons receiving inputs from the urinary bladder; and this mechanism may play a role in the activation and maintenance of primary central sensitization to noxious visceral stimuli.
Calcium Signaling Mediated by P2Y Receptors in Mouse Taste Cells
Authors: Baryshnikov Sergey G. , Rogachevskaja Olga A. , Kolesnikov Stanislav S.
Published: May 2006

Evidence implicates a number of neuroactive substances and their receptors in mediating complex cell-to-cell communications in the taste bud. Recently, we found that ATP, a ubiquitous neurotransmitter/neuromodulator, mobilizes intracellular Ca2+in taste cells by activating P2Y receptors. Here, P2Y receptor-cellular response coupling was characterized in detail using single cell ratio photometry and the inhibitory analysis. The sequence of underlying events was shown to include ATP-dependent activation of PLC, IP3production, and IP3receptor-mediated Ca2+release followed by Ca2+influx. Data obtained favor SOC channels rather than receptor-operated channels as a pathway for Ca2+influx that accompanies Ca2+release. Intracellular Ca2+mobilized by ATP is apparently extruded by the plasma membrane Ca2+-ATPase, while a contribution of the Na+/Ca2+exchange and other mechanisms of Ca2+clearance is negligible. Cyclic AMP-dependent phosphorylation is likely to control a gain of the phosphoinositide cascade involved in ATP transduction. ATP-responsive taste cells are abundant in circumvallate, foliate, and fungiform papillae. Taken together, our observations point to a putative role for ATP as a neurotransmitter operative in the taste bud.
Dynamics of Abducens Nucleus Neuron Discharges During Disjunctive Saccades
Authors: Sylvestre Pierre A. , Cullen Kathleen E.
Published: May 2006

In this report, we provide the first characterization of abducens nucleus neuron (ABN) discharge dynamics during horizontal disjunctive saccades. These movements function to rapidly transfer the visual axes between targets located at different eccentricities and depths. Our primary objective was to determine whether the signals carried by ABNs during these movements are appropriate to drive the motion of the eye to which they project. We also asked whether ABNs encode eye movements similarly during disjunctive saccades and disjunctive fixation. To address the first objective we 1) assessed whether we could predict the discharge dynamics of individual neurons during disjunctive saccades based on their discharge properties during conjugate saccades and 2) directly estimated the sensitivity of individual neurons to either the ipsilateral/contralateral eye or the conjugate/vergence position and velocity using bootstrap statistics. Our main finding was that during disjunctive saccades in the direction ipsilateral to the recording site (on-direction), the majority of ABNs preferentially encoded the velocity and the position of the ipsilateral eye. The remaining neurons predominantly encoded the conjugate motion of the eyes (i.e., were equally sensitive to the motion of both eyes). Generally, ipsilateral/contralateral eye based models better described neuronal discharges than conjugate/vergence based models, yet both model structures yielded similar conclusions. Moreover, the preferred eye of individual neurons based on their position and velocity sensitivities were generally well matched. We also found that for saccades in the off-direction, the pausing behavior of ABNs was similar during conjugate and disjunctive saccades, with the exception that for movements of small amplitudes, more ABNs paused during conjugate saccades. Finally, we found that putative motoneurons and internuclear neurons encoded on- and off-direction disjunctive saccades in a similar manner. To address our second objective, we compared the discharge properties of individual ABNs during disjunctive saccades and disjunctive fixation. Good coherence was observed between the preferred eye of individual ABNs during the two behaviors. Taken together, our results indicate that although individual ABNs can encode the motion of both eyes to various degrees, the population drive of ABNs accounts for most of the movement of the ipsilateral eye during disjunctive saccades and disjunctive fixation.
Mechanisms of Dopamine Activation of Fast-Spiking Interneurons That Exert Inhibition in Rat Prefrontal Cortex
Authors: Gorelova Natalia , Seamans Jeremy K. , Yang Charles R.
Published: May 2006

Prefrontal cortical dopamine (DA) modulates pyramidal cell excitability directly and indirectly by way of its actions on local circuit GABAergic interneurons. DA modulation of interneuronal functions is implicated in the computational properties of prefrontal networks during cognitive processes and in schizophrenia. Morphologically and electrophysiologically distinct classes of putative GABAergic interneurons are found in layers II-V of rat prefrontal cortex. Our whole cell patch-clamp study shows that DA induced a direct, TTX-insensitive, reversible membrane depolarization, and increased the excitability of fast-spiking (FS) interneurons. The DA-induced membrane depolarization was reduced significantly by D1/D5 receptor antagonist SCH 23390, but not by the D2 receptor antagonist (−)sulpiride, D4 receptor antagonists U101958 or L-745870, α1-adrenoreceptor antagonist prazosin, or serotoninergic receptor antagonist mianserin. The D1/5 agonists SKF81297 or dihydrexidine, but not D2 agonist quinpirole, also induced a prolonged membrane depolarization. Voltage-clamp analyses of the voltage-dependence of DA-sensitive currents, and the effects of changing [K+]Oon reversal potentials of DA responses, revealed that DA suppressed a Cs+-sensitive inward rectifier K+current and a resting leak K+current. D1/D5, but not D2 agonists mimicked the suppressive effects of DA on the leak current, but the DA effects on the inward rectifier K+current were not mimicked by either agonist. In a subgroup of FS interneurons, the slowly inactivating membrane outward rectification evoked by depolarizing voltage steps was also attenuated by DA. Collectively, these data showed that DA depolarizes FS interneurons by suppressing a voltage-independent ‘leak’ K+current (via D1/D5 receptor mechanism) and an inwardly rectifying K+current (via unknown DA mechanisms). Additional suppression of a slowly inactivating K+current led to increase in repetitive firing in response to depolarizing inputs. This D1-induced increase in interneuron excitability enhances GABAergic transmission to PFC pyramidal neurons and could represent a mechanism via which DA suppresses persistent firing of pyramidal neurons in vivo.
Anterior Inferotemporal Neurons of Monkeys Engaged in Object Recognition Can be Highly Sensitive to Object Retinal Position
Authors: DiCarlo James J. , Maunsell John H. R.
Published: May 2006

Visual object recognition is computationally difficult because changes in an object's position, distance, pose, or setting may cause it to produce a different retinal image on each encounter. To robustly recognize objects, the primate brain must have mechanisms to compensate for these variations. Although these mechanisms are poorly understood, it is thought that they elaborate neuronal representations in the inferotemporal cortex that are sensitive to object form but substantially invariant to other image variations. This study examines this hypothesis for image variation resulting from changes in object position. We studied the effect of small differences (±1.5°) in the retinal position of small (0.6° wide) visual forms on both the behavior of monkeys trained to identify those forms and the responses of 146 anterior IT (AIT) neurons collected during that behavior. Behavioral accuracy and speed were largely unaffected by these small changes in position. Consistent with previous studies, many AIT responses were highly selective for the forms. However, AIT responses showed far greater sensitivity to retinal position than predicted from their reported receptive field (RF) sizes. The median AIT neuron showed a ∼60% response decrease between positions within ±1.5° of the center of gaze, and 52% of neurons were unresponsive to one or more of these positions. Consistent with previous studies, each neuron's rank order of target preferences was largely unaffected across position changes. Although we have not yet determined the conditions necessary to observe this marked position sensitivity in AIT responses, we rule out effects of spatial-frequency content, eye movements, and failures to include the RF center. To reconcile this observation with previous studies, we hypothesize that either AIT position sensitivity strongly depends on object size or that position sensitivity is sharpened by extensive visual experience at fixed retinal positions or by the presence of flanking distractors.
Patterns of Canal and Otolith Afferent Input Convergence in Frog Second-Order Vestibular Neurons
Authors: Straka H. , Holler S. , Goto F.
Published: May 2006

Second-order vestibular neurons (2°VN) were identified in the isolated frog brain by the presence of monosynaptic excitatory postsynaptic potentials (EPSPs) after separate electrical stimulation of individual vestibular nerve branches. Combinations of one macular and the three semicircular canal nerve branches or combinations of two macular nerve branches were stimulated separately in different sets of experiments. Monosynaptic EPSPs evoked from the utricle or from the lagena converged with monosynaptic EPSPs from one of the three semicircular canal organs in ∼30% of 2°VN. Utricular afferent signals converged predominantly with horizontal canal afferent signals (74%), and lagenar afferent signals converged with anterior vertical (63%) or posterior vertical (37%) but not with horizontal canal afferent signals. This convergence pattern correlates with the coactivation of particular combinations of canal and otolith organs during natural head movements. A convergence of afferent saccular and canal signals was restricted to very few 2°VN (3%). In contrast to the considerable number of 2°VN that received an afferent input from the utricle or the lagena as well as from one of the three canal nerves (∼30%), smaller numbers of 2°VN (14% of each type of 2°otolith or 2°canal neuron) received an afferent input from only one particular otolith organ or from only one particular semicircular canal organ. Even fewer 2°VN received an afferent input from more than one semicircular canal or from more than one otolith nerve (∼7% each). Among 2°VN with afferent inputs from more than one otolith nerve, an afferent saccular nerve input was particularly rare (4–5%). The restricted convergence of afferent saccular inputs with other afferent otolith or canal inputs as well as the termination pattern of saccular afferent fibers are compatible with a substrate vibration sensitivity of this otolith organ in frog. The ascending and/or descending projections of identified 2°VN were determined by the presence of antidromic spikes. 2°VN mediating afferent utricular and/or semicircular canal nerve signals had ascending and/or descending axons. 2°VN mediating afferent lagenar or saccular nerve signals had descending but no ascending axons. The latter result is consistent with the absence of short-latency macular signals on extraocular motoneurons during vertical linear acceleration. Comparison of data from frog and cat demonstrated the presence of a similar organization pattern of maculo- and canal-ocular reflexes in both species.
Episodic Bouts of Activity Accompany Recovery of Rhythmic Output By a Neuromodulator- and Activity-Deprived Adult Neural Network
Authors: Luther Jason A. , Robie Alice A. , Yarotsky John , Reina Christopher , Marder Eve , Golowasch Jorge
Published: May 2006

The pyloric rhythm of the stomatogastric ganglion of the crab, Cancer borealis, slows or stops when descending modulatory inputs are acutely removed. However, the rhythm spontaneously resumes after one or more days in the absence of neuromodulatory input. We recorded continuously for days to characterize quantitatively this recovery process. Activity bouts lasting 40–900 s began several hours after removal of neuromodulatory input and were followed by stable rhythm recovery after 1–4 days. Bout duration was not related to the intervals (0.3–800 min) between bouts. During an individual bout, the frequency rapidly increased and then decreased more slowly. Photoablation of back-filled neuromodulatory terminals in the stomatogastric ganglion (STG) neuropil had no effect on activity bouts or recovery, suggesting that these processes are intrinsic to the STG neuronal network. After removal of neuromodulatory input, the phase relationships of the components of the triphasic pyloric rhythm were altered, and then over time the phase relationships moved toward their control values. Although at low pyloric rhythm frequency the phase relationships among pyloric network neurons depended on frequency, the changes in frequency during recovery did not completely account for the change in phase seen after rhythm recovery. We suggest that activity bouts represent underlying mechanisms controlling the restructuring of the pyloric network to allow resumption of an appropriate output after removal of neuromodulatory input.
Segregation of on and offRetinogeniculate Connectivity Directed by Patterned Spontaneous Activity
Authors: Lee Christopher W. , Eglen Stephen J. , Wong Rachel O. L.
Published: May 2006

In many parts of the developing nervous system, the early patterns of connectivity are refined by processes that require neuronal activity. These processes are thought to involve Hebbian mechanisms that lead to strengthening and maintenance of inputs that display correlated pre- and postsynaptic activity and elimination of inputs that fire asynchronously. Here we investigated the role of patterned spontaneous retinal activity and Hebbian synaptic mechanisms on segregation of on and off retinal afferents in the dorsal lateral geniculate nucleus (dLGN) of the developing ferret visual system. We recorded extracellularly the spontaneous spike activity of neighboring pairs of ganglion cells and found thatoff cells have significantly higher mean firing rates thanon cells. Spiking is best correlated between cells of the same sign (on, on; off,off) compared with cells of opposite sign (on,off). We then constructed a simple Hebbian model of retinogeniculate synaptic development based on a correlational framework. Using our recorded activity patterns, together with previous calcium-imaging data, we show that endogenous retinal activity, coupled with Hebbian mechanisms of synaptic development, can drive the segregation of on and off retinal inputs to the dLGN. Segregation occurs robustly when heterosynaptic competition is present within time windows of 50–500 ms. In addition, our results suggest that the initial patterns of connectivity (biases in convergence of inputs) and the strength of inhibition in the network each play a crucial role in determining whether on oroff inputs dominate at maturity.
Spreading Depression Can Be Elicited in Brain Stem of Immature But Not Adult Rats
Authors: Richter Frank , Rupprecht Sven , Lehmenkühler Alfred , Schaible Hans-Georg
Published: May 2006

Spreading depression (SD), a neuronal mechanism involved in brain pathophysiology, occurs in brain areas with high neuronal density such as the cerebral cortex. By contrast, the brain stem is thought to be resistant to SD. Here we show that DC shifts resembling cortical SD can be elicited in rat brain stem by topical application of KCl but not by pricking the brain stem. However, this was only possible until postnatal day 13, and, in addition, susceptibility for SD had to be enhanced. The latter was achieved by superfusion of the brain stem for 45 min with a solution containing acetate instead of chloride ions. Transient asphyxia or hypoxia by 2 min breathing 6% O2in N2had a similar effect. Negative brain stem DC deflections were paralleled by an increase of extracellular potassium concentration ≤40 mM and were spreading, but unlike cortical SD they were not inducible by glutamate and N-methyl-d-aspartate (NMDA). Time course and slope of brain stem SD either resembled cortical SD or were long-lasting and sustained. The latter stopped normal breathing. Different from cortical SD, negative brain stem DC deflections were changed in their slope (mostly converted into sustained shape, peak time was significantly prolonged, decline-time and duration were prolonged), but not abolished by the NMDA receptor blocker MK-801. Thus we demonstrate that the immature brain stem has the capacity to generate negative DC shifts, which could be relevant as a risk factor in newborn brain stem function.
Selective Regulation of xSlo Splice Variants DuringXenopusEmbryogenesis
Authors: Kukuljan Manuel , Taylor Alison , Chouinard Hilary , Olguín Patricio , Rojas Cecilia V. , Ribera Angeles B.
Published: May 2006

Calcium-activated potassium channels regulate excitability of the adult nervous system. In contrast, little is known about the contribution of calcium-activated potassium channels to excitability of the embryonic nervous system when electrical membrane properties and intracellular calcium levels show dramatic changes. Embryonic Xenopus spinal neurons exhibit a well-characterized developmental program of excitability that involves several different currents including calcium-activated ones. Here, we show that a molecular determinant of calcium-activated potassium channels, xSlo, is expressed during Xenopus embryogenesis even prior to differentiation of excitable tissues. Five different xSlo variants are expressed in embryonic tissues as a consequence of alternative exon usage at a single splice site. One of these variants, xSlo59, is neural-specific, and its expression is limited to late stages of neuronal differentiation. However, expression of the four other variants occurs in both muscle and neurons at all stages of development examined. Electrophysiological analysis of recombinant xSlo channels reveals that the xSlo59 exon serves as a gain-of-function module and allows physiologically relevant levels of membrane potential and intracellular calcium to activate effectively the resultant channel. These results suggest that xSlo59 channels play a unique role in sculpting the excitable membrane properties of Xenopus spinal neurons.
Two Different Types of Y Cells in the Cat Lateral Geniculate Nucleus
Authors: Yeh Chun-I , Stoelzel Carl R. , Alonso Jose-Manuel
Published: May 2006

The Y pathway in the cat visual system is traditionally viewed as a single channel that originates in the retina. However, most Y cells from the contralateral retina diverge to innervate two different layers of the lateral geniculate nucleus, suggesting a possible channel split: YC (Y geniculate cell in layer C) and YA (Y geniculate cell in layer A). We tested the functional significance of this anatomical divergence by comparing the response properties of simultaneously recorded YC and YA geniculate cells with overlapping receptive fields. Our results demonstrate that YC and YA cells significantly differ in a large number of temporal and spatial parameters including response latency, response transiency, receptive-field size, and linearity of spatial summation. Furthermore, for some of these parameters, the differences between YC and YA cells are as pronounced as the differences between Y and X cells in layer A. These results along with results from previous studies strongly suggest that Y retinal afferents diverge into two separate channels at the level of the thalamus.
Capsaicin Infused Into the PAG Affects Rat Tail Flick Responses to Noxious Heat and Alters Neuronal Firing in the RVM
Authors: McGaraughty Steve , Chu Katharine L. , Bitner Robert S. , Martino Brenda , Kouhen Rachid El , Han Ping , Nikkel Arthur L. , Burgard Edward C. , Faltynek Connie R. , Jarvis Michael F.
Published: May 2006

It is well established that the vanilloid receptor, VR1, is an important peripheral mediator of nociception. VR1 receptors are also located in several brain regions, yet it is uncertain whether these supraspinal VR1 receptors have any influence on the nociceptive system. To investigate a possible nociceptive role for supraspinal VR1 receptors, capsaicin (10 nmol in 0.4 μl) was microinjected into either the dorsal (dPAG) or ventral (vPAG) regions of the periaqueductal gray. Capsaicin-related effects on tail flick latency (immersion in 52°C water) and on neuronal activity (on-, off-, and neutral cells) in the rostral ventromedial medulla (RVM) were measured in lightly anesthetized rats. Administration of capsaicin into the dPAG but not the vPAG caused an initial hyperalgesic response followed later by analgesia (125 ± 20.96 min postinjection). The tail flick–related burst in on-cell activity was triggered earlier in the hyperalgesic phase and was delayed or absent during the analgesic phase. Spontaneous activity of on-cells increased at the onset of the hyperalgesic phase and decreased before and during the analgesic phase. The tail flick–related pause in off-cell activity as well as spontaneous firing for these cells was unchanged in the hyperalgesic phase. During the analgesic phase, off-cells no longer paused during noxious stimulation and had increased levels of spontaneous activity. Neutral cell firing was unaffected in either phase. Pretreatment with the VR1 receptor antagonist, capsazepine (10 nmol in 0.4 μl), into the dPAG blocked the capsaicin-induced hyperalgesia as well as the corresponding changes in on- and off-cell activity. VR1 receptor immunostaining was observed in the dPAG of untreated rats. Microinjection of capsaicin likely sensitized and then desensitized dPAG neurons affecting nocifensive reflexes and RVM neuronal activity. These results suggest that supraspinal VR1 receptors in the dPAG contribute to descending modulation of nociception.
Depolarization Block of Neurons During Maintenance of Electrographic Seizures
Authors: Bikson Marom , Hahn Philip J. , Fox John E. , Jefferys John G.R.
Published: May 2006

Epileptic seizures are associated with neuronal hyperactivity. Here, however, we investigated whether continuous neuronal firing is necessary to maintain electrographic seizures. We studied a class of “low-Ca2+” ictal epileptiform bursts, induced in rat hippocampal slices, that are characterized by prolonged (2–15 s) interruptions in population spike generation. We found that, during these interruptions, neuronal firing was suppressed rather than desynchronized. Intracellular current injection, application of extracellular uniform electric fields, and antidromic stimulation showed that the source of action potential disruption was depolarization block. The duration of the extracellular potassium transients associated with each ictal burst was not affected by disruptions in neuronal firing. Application of phenytoin or veratridine indicated a critical role for the persistent sodium current in maintaining depolarization block. Our results show that continuous neuronal firing is not necessary for the maintenance of experimental electrographic seizures.