bluuebunny/crossref_metadata_2025 huggingface dataset:
Fast Synaptic Connections From CBIs to Pattern-Generating Neurons inAplysia: Initiation and Modification of Motor Programs
Authors: Hurwitz Itay , Kupfermann Irving , Weiss Klaudiusz R.
Published: May 2006

Consummatory feeding movements in Aplysia californica are organized by a central pattern generator (CPG) in the buccal ganglia. Buccal motor programs similar to those organized by the CPG are also initiated and controlled by the cerebro-buccal interneurons (CBIs), interneurons projecting from the cerebral to the buccal ganglia. To examine the mechanisms by which CBIs affect buccal motor programs, we have explored systematically the synaptic connections from three of the CBIs (CBI-1, CBI-2, CBI-3) to key buccal ganglia CPG neurons (B31/B32, B34, and B63). The CBIs were found to produce monosynaptic excitatory postsynaptic potentials (EPSPs) with both fast and slow components. In this report, we have characterized only the fast component. CBI-2 monosynaptically excites neurons B31/B32, B34, and B63, all of which can initiate motor programs when they are sufficiently stimulated. However, the ability of CBI-2 to initiate a program stems primarily from the excitation of B63. In B31/B32, the size of the EPSPs was relatively small and the threshold for excitation was very high. In addition, preventing firing in either B34 or B63 showed that only a block in B63 firing prevented CBI-2 from initiating programs in response to a brief stimulus. The connections from CBI-2 to the buccal ganglia neurons showed a prominent facilitation. The facilitation contributed to the ability of CBI-2 to initiate a BMP and also led to a change in the form of the BMP. The cholinergic blocker hexamethonium blocked the fast EPSPs induced by CBI-2 in buccal ganglia neurons and also blocked the EPSPs between a number of key CPG neurons within the buccal ganglia. CBI-2 and B63 were able to initiate motor patterns in hexamethonium, although the form of a motor pattern was changed, indicating that non-hexamethonium-sensitive receptors contribute to the ability of these cells to initiate bursts. By contrast to CBI-2, CBI-1 excited B63 but inhibited B34. CBI-3 excited B34 and not B63. The data indicate that CBI-1, -2, and -3 are components of a system that initiates and selects between buccal motor programs. Their behavioral function is likely to depend on which combination of CBIs and CPG elements are activated.
Responses of Primate Caudal Parabrachial Nucleus and Kölliker-Fuse Nucleus Neurons to Whole Body Rotation
Authors: Balaban Carey D. , McGee David M. , Zhou Jianxun , Scudder Charles A.
Published: May 2006

The caudal aspect of the parabrachial (PBN) and Kölliker-Fuse (KF) nuclei receive vestibular nuclear and visceral afferent information and are connected reciprocally with the spinal cord, hypothalamus, amygdala, and limbic cortex. Hence, they may be important sites of vestibulo-visceral integration, particularly for the development of affective responses to gravitoinertial challenges. Extracellular recordings were made from caudal PBN cells in three alert, adult female Macaca nemestrina through an implanted chamber. Sinusoidal and position trapezoid angular whole body rotation was delivered in yaw, roll, pitch, and vertical semicircular canal planes. Sites were confirmed histologically. Units that responded during rotation were located in lateral and medial PBN and KF caudal to the trochlear nerve at sites that were confirmed anatomically to receive superior vestibular nucleus afferents. Responses to whole-body angular rotation were modeled as a sum of three signals: angular velocity, a leaky integration of angular velocity, and vertical position. All neurons displayed angular velocity and integrated angular velocity sensitivity, but only 60% of the neurons were position-sensitive. These responses to vertical rotation could display symmetric, asymmetric, or fully rectified cosinusoidal spatial tuning about a best orientation in different cells. The spatial properties of velocity and integrated velocity and position responses were independent for all position-sensitive neurons; the angular velocity and integrated angular velocity signals showed independent spatial tuning in the position-insensitive neurons. Individual units showed one of three different orientations of their excitatory axis of velocity rotation sensitivity: vertical-plane-only responses, positive elevation responses (vertical plane plus ipsilateral yaw), and negative elevation axis responses (vertical plane plus negative yaw). The interactions between the velocity and integrated velocity components also produced variations in the temporal pattern of responses as a function of rotation direction. These findings are consistent with the hypothesis that a vestibulorecipient region of the PBN and KF integrates signals from the vestibular nuclei and relay information about changes in whole-body orientation to pathways that produce homeostatic and affective responses.
A Role for Myotonic Dystrophy Protein Kinase in Synaptic Plasticity
Authors: Schulz Paul E. , McIntosh Adeka D. , Kasten Michael R. , Wieringa Berend , Epstein Henry F.
Published: May 2006

Myotonic dystrophy (DM) is associated with an expanded triplet repeat in the 3′-untranslated region of the gene for myotonic dystrophy protein kinase (DMPK), which may reduce DMPK expression. It is unclear how reduced DMPK expression might contribute to the symptoms of DM because the normal function of DMPK is not yet understood. Thus we investigated the function of DMPK to gain insight into how reduced DMPK expression might lead to cognitive dysfunction in DM. We recently demonstrated a role for DMPK in modifying the cytoskeleton, and remodeling of the cytoskeleton is thought to be important for cognitive function. Therefore we hypothesized that DMPK might normally contribute to synaptic plasticity and cognitive function via an effect on actin cytoskeletal rearrangements. To test for involvement of DMPK in synaptic plasticity, we utilized the DMPK null mouse. This mouse showed no changes in baseline synaptic transmission in hippocampal area CA1, nor any changes in long-term synaptic potentiation (LTP) measured 3 h after induction. There was a significant decrease, however, in the decremental potentiation with a duration of 30–180 min that accompanies LTP. These results suggest a role for DMPK in synaptic plasticity that could be relevant to the cognitive dysfunction associated with DM.
ATP Released From Astrocytes During Swelling Activates Chloride Channels
Authors: Darby Mark , Kuzmiski J. Brent , Panenka William , Feighan Denise , MacVicar Brian A.
Published: May 2006

ATP release from astrocytes contributes to calcium ([Ca2+]) wave propagation and may modulate neuronal excitability. In epithelial cells and hepatocytes, cell swelling causes ATP release, which leads to the activation of a volume-sensitive Cl−current ( ICl,swell) through an autocrine pathway involving purinergic receptors. Astrocyte swelling is counterbalanced by a regulatory volume decrease, involving efflux of metabolites and activation of ICl,swelland K+currents. We used whole cell patch-clamp recordings in cultured astrocytes to investigate the autocrine role of ATP in the activation of ICl,swellby hypo-osmotic solution (HOS). Apyrase, an ATP/ADP nucleotidase, inhibited HOS-activated ICl,swell, whereas ATP and the P2Y agonists, ADPβS and ADP, induced Cl−currents similar to ICl,swell. Neither the P2U agonist, UTP nor the P2X agonist, α,β-methylene ATP, were effective. BzATP was less effective than ATP, suggesting that P2X7 receptors were not involved. P2 purinergic antagonists, suramin, RB2, and pyridoxalphosphate-6-azophenyl-2′,4′-disulfonic acid (PPADS) reversibly inhibited activation of ICl,swell, suggesting that ATP-activated P2Y1 receptors. Thus ATP release mediates ICl,swellin astrocytes through the activation of P2Y1-like receptors. The multidrug resistance protein (MRP) transport inhibitors probenicid, indomethacin, and MK-571 all potently inhibited ICl.swell. ATP release from astrocytes in HOS was observed directly using luciferin-luciferase and MK-571 reversibly depressed this HOS-induced ATP efflux. We conclude that ATP release via MRP and subsequent autocrine activation of purinergic receptors contributes to the activation of ICl,swellin astrocytes by HOS-induced swelling.
Defensive Movements Evoked by Air Puff in Monkeys
Authors: Cooke Dylan F. , Graziano Michael S. A.
Published: May 2006

Electrical stimulation of two connected cortical areas in the monkey brain, the ventral intraparietal area (VIP) in the intraparietal sulcus and the polysensory zone (PZ) in the precentral gyrus, evokes a specific set of movements. In one interpretation, these movements correspond to those typically used to defend the body from objects that are near, approaching, or touching the skin. The present study examined the movements evoked by a puff of air aimed at various locations on the face and body of fascicularis monkeys to compare them to the movements evoked by stimulation of VIP and PZ. The air-puff-evoked movements included a movement of the eyes from any initial position toward a central region and a variety of stereotyped facial, shoulder, head, and arm movements. These movements were similar to those reported on stimulation of VIP and PZ. One difference between the air-puff-evoked movements and those evoked by stimulation of VIP and PZ is that the air puff evoked an initial startle response (a bilaterally symmetric spike in muscle activity) followed by a more sustained, lateralized response, specific to the site of the air puff. In contrast, stimulation of VIP and PZ evoked mainly a sustained, lateralized response, specific to the site of the receptive fields of the stimulated neurons. We speculate that VIP and PZ may contribute to the control of defensive movements, but that they may emphasize the more spatially specific reactions that occur after startle.
Representations of the Texture of Food in the Primate Orbitofrontal Cortex: Neurons Responding to Viscosity, Grittiness, and Capsaicin
Authors: Rolls Edmund T. , Verhagen Justus V. , Kadohisa Mikiko
Published: May 2006

The primate orbitofrontal cortex (OFC) is a site of convergence from taste, olfactory, and somatosensory cortical areas. We describe a population of single neurons in the macaque OFC that responds to the texture of food in the mouth. Use of oral viscosity stimuli consisting of carboxymethylcellulose (CMC) in the range 1–10,000 centipoise showed that the responses of one subset of these neurons were related to stimulus viscosity. Some of the neurons had increasing responses to increasing viscosity, some had decreasing responses, and some neurons were tuned to a range of viscosities. These neurons are a different population to oral fat-sensitive neurons, in that their responses to fats (e.g., safflower oil), to silicone oil [(Si(CH3)2O)n], and to mineral oil (hydrocarbon) depended on the viscosity of these oils. Thus there is a dissociation between texture channels used to sense viscosity and fat. Some of these viscosity-sensitive single neurons were unimodal (somatosensory; 25%) and some received convergent taste inputs (75%). A second subpopulation of neurons responded to gritty texture (produced by microspheres suspended in CMC). A third subpopulation of neurons responded to capsaicin. These results provide evidence about the information channels used to represent the texture and flavor of food in a part of the brain important in appetitive responses to food and are relevant to understanding the physiological and pathophysiological processes related to food intake, food selection, and the effects of variety of food texture in combination with taste and other inputs that affect food intake.
Inter-Ictal- and Ictal-Like Epileptic Discharges in the Dendritic Tree of Neocortical Pyramidal Neurons
Authors: Schiller Yitzhak
Published: May 2006

Dendritic mechanisms have been implied to play a key role in the formation of epileptic discharges. However, presently only a handful of direct dendritic recordings have been reported during epileptic discharges. In this study, I performed simultaneous voltage recordings from the soma and apical dendrite of the same neuron combined with calcium-imaging measurements to investigate inter-ictal- and ictal-like epileptic discharges in dendrites of layer 5 pyramidal neurons. Neocortical brain slices treated with bicuculline (BCC) produced both isolated “inter-ictal” paroxysymal depolarization shift (PDS) responses and electrographic seizures. Concomitant voltage recordings from the soma and apical dendrite revealed that PDS responses developed in both the apical dendrites and soma. However, the two responses differed from one another. In apical dendrites, the PDS was significantly higher in amplitude and shorter in duration compared with the somatic PDS. The PDS response in dendrites had a peak amplitude of 68.9 ± 2.2 (SD) mV, peak voltage value of 9.3 ± 2.7 mV, and half-width of 203.8 ± 38.4 ms. In contrast, the somatic PDS had a peak amplitude of 48.7 ± 2.7 mV, peak voltage value of −11.9 ± 3.1 mV, and half-width of 247.8 ± 57.3 ms ( P < 0.01, n = 18). In addition the apical dendritic PDS always preceded the somatic counterpart in all 18 neurons examined. Concomitant calcium-imaging measurements showed the PDS evoked large calcium influx into the entire dendritic tree including the apical tuft, basal, and oblique dendrites. The PDS evoked [Ca2+]i were not uniform along the dendritic tree, being highest in the oblique dendrites (71.3 ± 14.5 μM) and lowest at the distal tuft branches (9.3 ± 0.7 μM). The PDS responses persisted after blockade of voltage-gated sodium channels by intracellular QX-314 but became narrower (by 69.6 ± 9.7%) following intracellular administration of the voltage-gated calcium channel blocker D600. Electrographic seizures recorded in the soma and apical dendrites were composed of recurrent bursts. The initial bursts represented PDS responses. During the seizure the amplitude of bursts gradually attenuated and reached an average value of 26 ± 13% of the initial ictal PDS burst. Double recordings during electrographic seizures revealed the initial one to four ictal bursts appeared first at the apical dendrite while later ictal bursts were always observed first at the soma. In conclusion, the results of this study show “inter-ictal” PDS responses originated in the apical dendritic tree, were partially mediated by voltage-gated calcium channels and spread throughout the dendritic tree including the fine tuft, basal, and oblique dendrites. During electrographic seizures the origin of epileptic bursts shifted from the apical dendritic tree to the soma-basal region.
Modulation of Cochlear Afferent Response by the Lateral Olivocochlear System: Activation Via Electrical Stimulation of the Inferior Colliculus
Authors: Groff J. Alan , Liberman M. Charles
Published: May 2006

The olivocochlear (OC) efferent innervation of the mammalian inner ear consists of two subdivisions, medial (MOC) and lateral (LOC), with different peripheral terminations on outer hair cells and cochlear afferent terminals, respectively. The cochlear effects of electrically activating MOC efferents are well known, i.e., response suppression effected by reducing outer hair cells' contribution to cochlear amplification. LOC peripheral effects are unknown, because their unmyelinated axons are difficult to electrically stimulate. Here, stimulating electrodes are placed in the inferior colliculus (IC) to indirectly activate the LOC system, while recording cochlear responses bilaterally from anesthetized guinea pigs. Shocks at some IC sites produced novel cochlear effects attributable to activation of the LOC system: long-lasting (5–20 min) enhancement or suppression of cochlear neural responses (compound action potentials and round window noise), without changes in cochlear responses dominated by outer hair cells (otoacoustic emissions and cochlear microphonics). These novel effects also differed from classic MOC effects in their lack of dependence on the level and frequency of the acoustic stimulus. These effects disappeared on sectioning the entire OC bundle, but not after selective lesioning of the MOC tracts or the cochlea's autonomic innervation. We conclude that the LOC pathway comprises two functional subdivisions, capable of inducing slow increases or decreases in response magnitudes in the auditory nerve. Such a system may be useful in maintaining accurate binaural comparisons necessary for sound localization in the face of slow changes in interaural sensitivity.
Endogenous Waves in Hippocampal Slices
Authors: Kubota Don , Colgin Laura Lee , Casale Malcolm , Brucher Fernando A. , Lynch Gary
Published: May 2006

Sharp waves (SPWs) are thought to play a major role in intrinsic hippocampal operations during states in which subcortical and cortical inputs to hippocampus are reduced. This study describes evidence that such activity occurs spontaneously in appropriately prepared rat hippocampal slices. Irregular waves, with an average frequency of approximately 4 Hz, were recorded from field CA3 in slices prepared from the temporal region of hippocampus. The waves persisted for hours and were not accompanied by aberrant discharges. Multi-electrode analyses established that they were locally generated within each of the subfields of CA3 and yet were coherent between subfields. The sharp waves were reversibly blocked by either cholinergic or serotonergic stimulation. Various lines of evidence indicate that they are propagated by the CA3 associational system.
Arachidonic Acid Metabolites Contribute to the Irreversible Depolarization Induced by In Vitro Ischemia
Authors: Tanaka E. , Niiyama S. , Sato S. , Yamada A. , Higashi H.
Published: May 2006

Intracellular recordings were made from hippocampal CA1 neurons in rat slice preparations. Superfusion with oxygen- and glucose-deprived medium (in vitro ischemia) produced a rapid depolarization ∼5 min after the onset of the superfusion. Even when oxygen and glucose were reintroduced immediately after rapid depolarization, the membrane depolarized further (persistent depolarization) and reached 0 mV (irreversible depolarization) after 5 min from the reintroduction. The pretreatment of the slice preparation with a phospholipase A2(PLA2) inhibitor, para-bromophenacyl bromide, or a cytochrome P-450 inhibitor, 17-octadecynoic acid, significantly restored the membrane to the preexposure potential level after the reintroduction of oxygen and glucose. The administration of 14,15-epoxyeicosatrienoic acid or 20-hydroxyeicosatetraenoic acid did not change the latency of the rapid depolarization and did not allow the membrane potential to recover after the ischemic exposure. In contrast, after pretreatment with cyclooxygenase or lipoxygenase inhibitors, such as indomethacin, resveratrol, Dup-697, nordihydroguaiaretic acid, and 3,4-dihydrophenyl ethanol, a minority of neurons tested showed postischemic recovery from the persistent depolarization. Improved recovery was also seen after treatment with the free radical scavengers, edaravone and α-tocopherol. These results suggest that the activation of the arachidonic acid cascade via PLA2and the free radicals produced by arachidonic acid metabolism contribute to the irreversible depolarization produced by in vitro ischemia.
Directional Sensitivity of Neurons in the Primary Auditory (AI) Cortex: Effects of Sound-Source Intensity Level
Authors: Reale Richard A. , Jenison Rick L. , Brugge John F.
Published: May 2006

Transient sounds were delivered from different directions in virtual acoustic space while recording from single neurons in primary auditory cortex (AI) of cats under general anesthesia. The intensity level of the sound source was varied parametrically to determine the operating characteristics of the spatial receptive field. The spatial receptive field was constructed from the onset latency of the response to a sound at each sampled direction. Spatial gradients of response latency composing a receptive field are due partially to a systematic co-dependence on sound-source direction and intensity level. Typically, at any given intensity level, the distribution of response latency within the receptive field was unimodal with a range of approximately 3–4 ms, although for some cells and some levels, the spread could be as much as 20 or as little as 2 ms. Response latency, averaged across directions, differed among neurons for the same intensity level, and also differed among intensity levels for the same neuron. Generally, increases in intensity level resulted in decreases in the mean and variance, which follows an inverse Gaussian distribution. Receptive field models, based on response latency, are developed using multiple parameters (azimuth, elevation, intensity), validated with Monte Carlo simulation, and their spatial filtering described using spherical harmonic analysis. Observations from an ensemble of modeled receptive fields are obtained by linking the inverse Gaussian density to the probabilistic inverse problem of estimating sound-source direction and intensity. Upper bounds on acuity is derived from the ensemble using Fisher information, and the predicted patterns of estimation errors are related to psychophysical performance.
Parvalbumin-Deficiency Facilitates Repetitive IPSCs and Gamma Oscillations in the Hippocampus
Authors: Vreugdenhil Martin , Jefferys John G. R. , Celio Marco R. , Schwaller Beat
Published: May 2006

In the hippocampus, the calcium-binding protein parvalbumin (PV) is expressed in interneurons that innervate perisomatic regions. PV in GABAergic synaptic terminals was proposed to limit repetitive GABA release by buffering of “residual calcium.” We assessed the role of presynaptic PV in Ca2+-dependent GABA release in the hippocampus of PV-deficient (PV−/−) mice and wild-type (PV+/+) littermates. Pharmacologically isolated inhibitory postsynaptic currents (IPSCs) were evoked by low-intensity stimulation of the stratum pyramidale and recorded from voltage-clamped CA1 pyramidal neurons. The amplitude and decay time constant of single IPSCs were similar for both genotypes. Under our experimental conditions of reduced release probability and minimal presynaptic suppression, paired-pulse facilitation of IPSCs occurred at intervals from 2 to 50 ms, irrespective of the presence of PV. The facilitation of IPSCs induced by trains of 10 stimuli at frequencies >20 Hz was enhanced in cells from PV−/− mice, the largest difference between PV−/− and PV+/+ animals (220%) being observed at 33 Hz. The effect of IPSC facilitation at sustained gamma frequencies was assessed on kainate-induced rhythmic IPSC-paced neuronal oscillations at gamma frequencies, recorded with dual field potential recordings in area CA3. The maximum power of the oscillation was 138 μV2 at 36 Hz in slices from PV+/+ mice and was trebled in slices from PV−/− mice. PV deficiency caused a similar increase in gamma power under conditions used to study IPSC facilitation and can be explained by an increased facilitation of GABA release at sustained high frequencies. The dominant frequency and coherence were not affected by PV deficiency. These observations suggest that PV deficiency, due to an increased short-term facilitation of GABA release, enhances inhibition by high-frequency burst-firing PV-expressing interneurons and may affect the higher cognitive functions associated with gamma oscillations.
Cortical Projection of Peripheral Vestibular Signaling
Authors: Emri Miklós , Kisely Mihály , Lengyel Zsolt , Balkay László , Márián Teréz , Mikó László , Berényi Ervin , Sziklai István , Trón Lajos , Tóth Ágnes
Published: May 2006

The cerebral projection of vestibular signaling was studied by using PET with a special differential experimental protocol. Caloric vestibular stimulation (CVS)-induced regional cerebral blood flow (rCBF) changes were investigated in two populations. Butanol perfusion scans were carried out on six healthy volunteers and on six patients following the removal of tumors from the right cerebello pontine angle. The complete loss of the vestibular function postoperatively allowed a comparison of the rCBF changes in the populations with or without this input and offered a promising functional approach whereby to delineate the cortical region most responsive to pure vestibular input. The activations by left-sided and right-sided CVS were determined for both the healthy volunteers and the patient population. Statistical analysis of the data obtained following left-sided CVS did not reveal any cerebral region for which there was a significant difference in CVS-induced response by these two populations. In the case of right-sided CVS, however, the statistical comparison of the CVS-related responses demonstrated a single contralateral area characterized by a significantly different degree of response. This cortical area corresponds to part of the cortical region described recently which can be activated by both CVS and neck vibration. It appears to be anatomically identical to the aggregate of the somatosensory area SII and the retroinsular cortex described in primates, a region identified by other investigators as an analog of the parietoinsular vestibular cortex.
Caffeine-Mediated Presynaptic Long-Term Potentiation in Hippocampal CA1 Pyramidal Neurons
Authors: Martín Eduardo D. , Buño Washington
Published: May 2006

We report a new form of long-term potentiation (LTP) in Schaffer collateral (SC)-CA1 pyramidal neuron synapses that originates presynaptically and does not require N-methyl-d-aspartate (NMDA) receptor activation nor increases in postsynaptic-free Ca2+. Using rat hippocampal slices, application of a brief “pulse” of caffeine in the bath evoked a nondecremental LTP (CAFLTP) of SC excitatory postsynaptic currents. An increased probability of transmitter release paralleled theCAFLTP, suggesting that it originated presynaptically. The P1adenosine receptor antagonist 8-cyclopentyltheophylline and the P2purinoreceptor antagonists suramin and piridoxal-5′-phosphate-azophenyl 2′,4′-disulphonate blocked theCAFLTP. Inhibition of Ca2+release from caffeine/ryanodine stores by bath-applied ryanodine inhibited theCAFLTP, but ryanodine in the pipette solution was ineffective, suggesting a presynaptic effect of ryanodine. Previous induction of the “classical” LTP did not prevent theCAFLTP, suggesting that the LTP and theCAFLTP have different underlying cellular mechanisms. TheCAFLTP is insensitive to the block of NMDA receptors by 2-amino-5-phosphonopentanoic acid and to Ca2+chelation with intracellular 1,2-bis (2-aminophenoxy) ethane- N,N,N′ ,N′-tetraacetic acid, indicating that neither postsynaptic NMDA receptors nor increases in cytosolic-free Ca2+participate in theCAFLTP. We conclude that theCAFLTP requires the interaction of caffeine with presynaptic P1, P2purinoreceptors, and ryanodine receptors and is caused by an increased probability of glutamate release at SC terminals.
Role of the Dorsolateral Pontine Nucleus in Short-Term Adaptation of the Horizontal Vestibuloocular Reflex
Authors: Ono Seiji , Das Vallabh E. , Mustari Michael J.
Published: May 2006

The dorsolateral pontine nucleus (DLPN) is a major component of the cortico-ponto-cerebellar pathway that carries signals essential for smooth pursuit. This pathway also carries visual signals that could play a role in visually guided motor learning in the vestibular ocular reflex (VOR). However, there have been no previous studies that tested this possibility directly. The aim of this study was to determine the potential role of the DLPN in short-term VOR gain adaptation produced by viewing a scene through lenses placed in front of both eyes. In control experiments, adaptation of VOR gain was achieved by sinusoidal rotation (0.2 Hz, 30°/s) for 2 h while the monkey viewed a stationary visual surround through either magnifying (×2) or minifying (×0.5) lenses. This led to increases (23–32%) or decreases (22–48%) of VOR gain as measured in complete darkness (VORd). We used injections of muscimol, a potent GABAA agonist (0.5 μl; 2%), to reversibly inactivate the DLPN, unilaterally, in three monkeys. After DLPN inactivation, initial acceleration of ipsilateral smooth-pursuit was reduced by 35–68%, and steady-state gain was reduced by 32–61%. Despite these significant deficits ( P < 0.01) in ipsilesional smooth pursuit, the VOR during lens viewing was similar to that measured in preinjection control experiments. Similarly, after 2 h of adaptation, VORd gain was not significantly different ( P > 0.61) from control adaptation values for either ipsi- or contralesional directions of head rotation. This was the case even though a stable ipsilesional smooth pursuit deficit persisted throughout the full adaptation period. Our results suggest that visual error signals for short-term adaptation of the VOR are derived from sources other than the DLPN perhaps including other basilar pontine nuclei and the accessory optic system.
Temporal and Spatial Profiles of Pontine-Evoked Monoamine Release in the Rat's Spinal Cord
Authors: Hentall Ian D. , Mesigil Riza , Pinzon Alberto , Noga Brian R.
Published: May 2006

In the spinal cord, the monoamine neurotransmitter norepinephrine, which is released mainly from fibers descending from the dorsal pons, has major modulatory effects on nociception and locomotor rhythms. To map the spatial and temporal patterns of this release, changes in monoamine level were examined in laminae I–VIII of lumbar segments L3–L6of halothane-anesthetized rats during pontine stimulation. The changes were measured through a carbon fiber microelectrode at 0.5-s intervals by fast cyclic voltammetry, which presently is the method of best spatiotemporal resolution. When different pontine sites were tested with 20-s pulse trains (50-to 200-μA amplitude, 0.5-ms pulse width, and 50-Hz frequency) during measurement in the dorsal horn (lamina IV), the largest consistent increases were produced by the locus ceruleus, although effective pontine sites extended 1.5 mm dorsally and ventral from the locus ceruleus. When the locus ceruleus stimulus was used to map the spinal cord, increased levels were always seen in lamina I and laminae IV–VIII, whereas 50% of sites in laminae II and III showed substantial decreases and the rest showed increases. These increases typically had short latencies [4.5 ± 0.4 (SE) s] and variable decay times (5–200 s), with peaks occurring during the stimulus train (mean rise-time: 12.0 ± 0.6 s). The mean peak level was 544 ± 82 nM as estimated from postexperimental calibration with norepinephrine. Other significant laminar differences included higher mean peak concentrations (805 nM) and rise times (14.9 s) in lamina I and shorter latencies in lamina VI (3.2 s). Peak concentrations were inversely correlated with latency. When stimulation frequency was varied, increases were disproportionately larger with faster frequencies (≥50 Hz), hence extrajunctional overflow probably contributed most of the signal. We conclude, generally, that pontine noradrenergic control is exerted on widespread spinal laminae with a significant component of paracrine transmission after several seconds of sustained activity. Relatively stronger effects prevail where nociceptive transmission (lamina I) and locomotor rhythm generation (lamina VI) occur.
Role of Cl–Co-Transporters in the Excitation Produced by GABAAReceptors in Juvenile Bovine Adrenal Chromaffin Cells
Authors: Xie Z. , Currie K.P.M. , Cahill A. L. , Fox A. P.
Published: May 2006

GABA is the primary inhibitory neurotransmitter in the adult mammalian brain. However, in neonatal animals, activation of Cl–-permeable GABA receptors is excitatory and appears to depend on the expression of a Na+-K+-2Cl–cotransporter (NKCC) that elevates intracellular Cl–levels, leading to a depolarized Cl–equilibrium potential ( ECl). The change from excitation to inhibition appears to involve the expression of the K+/Cl–co-transporter, KCC2, which lowers intracellular Cl–levels resulting in a hyperpolarized ECl. In this study, we show that bovine chromaffin cells from 4- to 5-mo-old animals are excited by GABA. Activation of GABAAreceptors depolarizes the cells, opens voltage-dependent Ca2+channels, elevates [Ca2+]i, and promotes the release of catecholamines. Blockade of voltage-dependent Ca2+channels prevents the elevation of [Ca2+]iby GABA. The extrapolated anion reversal potential in these cells is approximately –28 mV, indicating a resting intracellular anion concentration of approximately 50 mM. Expression of KCC2 protein was not detected in the juvenile chromaffin cells. In contrast, clear expression of NKCC1 was observed. Blockade of NKCC1 should reduce the intracellular Cl–concentration and hyperpolarize ECl. Bumetanide, an NKCC1 blocker, reduced the elevation of [Ca2+]iby GABA. In some cells, activation of GABAAreceptors inhibits responses to excitatory neurotransmitters, even though GABA itself is depolarizing. Co-activation of cholinergic and GABAAreceptors in chromaffin cells produced elevations in [Ca2+]ithat were comparable to those produced by cholinergic receptors alone. Our data showing the selective expression of chloride co-transporters and the resulting strongly depolarized anion reversal potential may help explain how activation of GABAAreceptors causes sufficient excitation to elicit catecholamine release from chromaffin cells.
Sensory-Motor Interaction in the Primate Auditory Cortex During Self-Initiated Vocalizations
Authors: Eliades Steven J. , Wang Xiaoqin
Published: May 2006

Little is known about sensory-motor interaction in the auditory cortex of primates at the level of single neurons and its role in supporting vocal communication. The present study investigated single-unit activities in the auditory cortex of a vocal primate, the common marmoset ( Callithrix jacchus), during self-initiated vocalizations. We found that 1) self-initiated vocalizations resulted in suppression of neural discharges in a majority of auditory cortical neurons. The vocalization-induced inhibition suppressed both spontaneous and stimulus-driven discharges. Suppressed units responded poorly to external acoustic stimuli during vocalization. 2) Vocalization-induced suppression began several hundred milliseconds prior to the onset of vocalization. 3) The suppression of cortical discharges reduced neural firings to below the rates expected from a unit's rate-level function, adjusted for known subcortical attenuation, and therefore was likely not entirely caused by subcortical attenuation mechanisms. 4) A smaller population of auditory cortical neurons showed increased discharges during self-initiated vocalizations. This vocalization-related excitation began after the onset of vocalization and is likely the result of acoustic feedback. Units showing this excitation responded nearly normally to external stimuli during vocalization. Based on these findings, we propose that the suppression of auditory cortical neurons, possibly originating from cortical vocal production centers, acts to increase the dynamic range of cortical responses to vocalization feedback for self monitoring. The excitatory responses, on the other hand, likely play a role in maintaining hearing sensitivity to the external acoustic environment during vocalization.
Quantification of Cardiac Sac Network Effects on a Movement-Related Parameter of Pyloric Network Output in the Lobster
Authors: Thuma Jeff B. , Hooper Scott L.
Published: May 2006

Cardiac sac network activity (cycle period tens of seconds to minutes) has long been known to alter pyloric network activity (cycle period approximately 1 s), but these effects have not been quantified. Some pyloric muscles extract cardiac sac timed variations in pyloric motor neuron firing, and consequently produce cardiac sac timed movements even though no cardiac sac neurons innervate them. Determining pyloric behavior therefore requires detailed description of cardiac sac effects on pyloric neural output. Pyloric muscle activity correlates well with motor neuron overall spike frequency (OSF, number of spikes per burst divided by cycle period). We therefore quantified the effects of cardiac sac activity on the OSF of all pyloric neurons in the lobster, Panulirus interruptus. The ventricular dilator (VD) neuron had a biphasic response, with its OSF first increasing and then decreasing during cardiac sac bursts. Lateral pyloric (LP) neuron OSF decreased during cardiac sac activity. The pyloric (PY) neurons had two responses, with OSF either decreasing or increasing just after the beginning of cardiac sac activity. The pyloric dilator (PD) neurons had a triphasic response, with OSF increasing slightly at the beginning of cardiac sac activity, decreasing during the cardiac sac burst, and strongly increasing after cardiac sac activity ended. The inferior cardiac (IC) neuron had a biphasic response, with OSF decreasing at the beginning of cardiac sac activity and strongly increasing when cardiac sac activity ceased. These data provide the quantitative description of cardiac sac effects on pyloric activity necessary to predict pyloric movement from pyloric neural output.
Magnetic Resonance Imaging of Human Extraocular Muscles in Convergence
Authors: Demer Joseph L. , Kono Reika , Wright Weldon
Published: May 2006

Extraocular muscle (EOM) paths during asymmetrical convergence were evaluated by tri-planar, contrast-enhanced magnetic resonance imaging of the orbits of eight young adults during binocular fixation of a target aligned to one eye at 800 and 15 cm distance. Cross sections and paths of EOMs were determined from area centroids. In convergence, the aligned eye rotated and translated negligibly, while its inferior oblique (IO) muscle exhibited significant contractile thickening. There were no significant contractile changes in the cross sections of aligned eye rectus or superior oblique (SO) muscles in convergence. The converging eye rotated nasally 22.4° but translated negligibly. The converging eye medial (MR) and lateral rectus (LR) muscles exhibited large contractile cross-section changes, and the IO showed significant contractile thickening, while the vertical rectus muscles and the SO did not. Anterior paths of three aligned eye rectus EOMs could be determined in convergence and shifted consistent with a 1.9° extorsion of the rectus pulley array. Such extorsional reconfiguration of the rectus pulleys would move the pulleys in coordination with globe extorsion and avoid imparting torsional action to these EOMs. Extorsional rectus pulley shift in convergence is inconsistent with the reconfiguration predicted to explain the temporal tilting of Listing's planes, instead suggesting that this temporal tilting is due to variations in oblique EOM innervation. Absence of globe translation in convergence argues against overall EOM co-contraction. The reconfiguration of EOM geometry in convergence has important implications for single-unit studies of neural control.
MSTd Neuronal Basis Functions for the Population Encoding of Heading Direction
Authors: Ben Hamed S. , Page W. , Duffy C. , Pouget A.
Published: May 2006

Basis functions have been extensively used in models of neural computation because they can be combined linearly to approximate any nonlinear functions of the encoded variables. We investigated whether dorsal medial superior temporal (MSTd) area neurons use basis functions to simultaneously encode heading direction, eye position, and the velocity of ocular pursuit. Using optimal linear estimators, we first show that the head-centered and eye-centered position of a focus of expansion (FOE) in optic flow, pursuit direction, and eye position can all be estimated from the single-trial responses of 144 MSTd neurons with an average accuracy of 2–3°, a value consistent with the discrimination thresholds measured in humans and monkeys. We then examined the format of the neural code for the head-centered position of the FOE, eye position, and pursuit direction. The basis function hypothesis predicts that a large majority of cells in MSTd should encode two or more signals simultaneously and combine these signals nonlinearly. Our analysis shows that 95% of the neurons encode two or more signals, whereas 76% code all three signals. Of the 95% of cells encoding two or more signals, 90% show nonlinear interactions between the encoded variables. These findings support the notion that MSTd may use basis functions to represent the FOE in optic flow, eye position, and pursuit.
Alternative to Hand-Tuning Conductance-Based Models: Construction and Analysis of Databases of Model Neurons
Authors: Prinz Astrid A. , Billimoria Cyrus P. , Marder Eve
Published: May 2006

Conventionally, the parameters of neuronal models are hand-tuned using trial-and-error searches to produce a desired behavior. Here, we present an alternative approach. We have generated a database of about 1.7 million single-compartment model neurons by independently varying 8 maximal membrane conductances based on measurements from lobster stomatogastric neurons. We classified the spontaneous electrical activity of each model neuron and its responsiveness to inputs during runtime with an adaptive algorithm and saved a reduced version of each neuron's activity pattern. Our analysis of the distribution of different activity types (silent, spiking, bursting, irregular) in the 8-dimensional conductance space indicates that the coarse grid of conductance values we chose is sufficient to capture the salient features of the distribution. The database can be searched for different combinations of neuron properties such as activity type, spike or burst frequency, resting potential, frequency–current relation, and phase-response curve. We demonstrate how the database can be screened for models that reproduce the behavior of a specific biological neuron and show that the contents of the database can give insight into the way a neuron's membrane conductances determine its activity pattern and response properties. Similar databases can be constructed to explore parameter spaces in multicompartmental models or small networks, or to examine the effects of changes in the voltage dependence of currents. In all cases, database searches can provide insight into how neuronal and network properties depend on the values of the parameters in the models.
Functional Excitatory Synapses in HEK293 Cells Expressing Neuroligin and Glutamate Receptors
Authors: Fu Zhanyan , Washbourne Philip , Ortinski Pavel , Vicini Stefano
Published: May 2006

The discovery that neuroligin is a key protein involved in synapse formation offers the unprecedented opportunity to induce functional synapses between neurons and heterologous cells. We took this opportunity recording for the first-time synaptic currents in human embryonic kidney 293 (HEK293) cells transfected with neuroligin and the N-methyl-d-aspartate or AMPA receptor subunits in a co-culture with rat cerebellar granule cells. These currents were similar to synaptic currents recorded in neurons, and their decay kinetics was determined by the postsynaptic subunit combination. Although neuroligin expression was sufficient to detect functional synapses, cotransfection of HEK293 cells with Postsynaptic density-95/synapse-associated protein-90 (PSD-95) significantly increased current frequency. Our results support the central role of neuroligin in the formation of CNS synapses, validate the proposal that PSD-95 allows synaptic maturation, and provide a unique experimental model to study how molecular components determine functional properties of excitatory synapses.
Endogenous Adenosine Reduces Glutamatergic Output From Rods Through Activation of A2-Like Adenosine Receptors
Authors: Stella Salvatore L. , Bryson Eric J. , Cadetti Lucia , Thoreson Wallace B.
Published: May 2006

Adenosine is released from retina in darkness; photoreceptors possess A2adenosine receptors, and A2agonists inhibit L-type Ca2+currents ( ICa) in rods. We therefore investigated whether A2agonists inhibit rod inputs into second-order neurons and whether selective antagonists to A1, A2A, or A3receptors prevent Ca2+influx through rod ICa. [Ca2+]ichanges in rods were assessed with fura-2. ICain rods and light responses of rods and second-order neurons were recorded using perforated patch-clamp techniques in the aquatic tiger salamander retinal slice preparation. Consistent with earlier results using the A2agonist N6-[2-(3,5-dimethoxyphenyl)-2-(2-methylphenyl)-ethyl]adenosine (DPMA), the A2Aagonist CGS-21680 significantly inhibited ICaand depolarization-evoked [Ca2+]iincreases in rods. The A1antagonist, 8-cyclopentyl-1,3-dipropylxanthine (DPCPX), and A2Aantagonist, ZM-241385, but not the A3antagonist, VUF-5574, inhibited effects of adenosine on Ca2+influx in rods. DPCPX and ZM-241385 also inhibited effects of CGS-21680, suggesting they both act at A2Areceptors. Both A2agonists, CGS-21680 and DPMA, reduced light-evoked currents in second-order neurons but not light-evoked voltage responses of rods, suggesting that activation of A2receptors inhibits transmitter release from rods. The inhibitory effects of CGS-21680 on both depolarization-evoked Ca2+influx and light-evoked currents in second-order neurons were antagonized by ZM-241385. By itself, ZM-241385 enhanced the light-evoked currents in second-order neurons, suggesting that endogenous levels of adenosine inhibit transmitter release from rods. The effects of these drugs suggest that endogenous adenosine activates an A2-like adenosine receptor on rods leading to inhibition of ICa, which in turn inhibits l-glutamate release from rod photoreceptors.
Accuracy, Information, and Response Time in a Saccadic Decision Task
Authors: Reddi B.A.J. , Asrress K. N. , Carpenter R.H.S.
Published: May 2006

Reaction times generally follow a simple law economically described by the LATER model, in which a decision signal rises linearly in response to information about a target to a threshold at which a response is initiated, at a rate that varies from trial to trial with a Gaussian distribution. Functionally, LATER may be regarded as an ideal decision mechanism incorporating prior probability, information, and criterion level or urgency; this can be tested quantitatively by seeing whether LATER accurately predicts the effects on latency distributions of manipulating these variables: in this case, information and urgency. We presented subjects with random-dot kinematograms while fixating a central LED. The information content of the display was varied by altering the proportion of the dots moving coherently together either left or right rather than randomly. As soon as subjects detected the direction of coherent movement, they made a saccade in the same direction to one of a pair of LEDs on each side of the fixation target. Subjects responded either carefully, taking time to ensure an accurate judgement, or more hastily and with less regard for accuracy. The distributions of latencies under the different combinations of conditions were found to conform to LATER's predictions. Providing more information or increasing urgency both reduce latency; but they alter the observed distributions in different ways, equivalent to increasing the mean rate of rise on the one hand or reducing the criterion level on the other. Making only simple assumptions about the underlying mechanisms, the observed changes can be accounted for quantitatively.