bluuebunny/crossref_metadata_2025 huggingface dataset:
Smooth-Pursuit Eye-Movement-Related Neuronal Activity in Macaque Nucleus Reticularis Tegmenti Pontis
Authors: Suzuki David A. , Yamada Tetsuto , Yee Robert D.
Published: May 2006

Neuronal responses that were observed during smooth-pursuit eye movements were recorded from cells in rostral portions of the nucleus reticularis tegmenti pontis (rNRTP). The responses were categorized as smooth-pursuit eye velocity (78%) or eye acceleration (22%). A separate population of rNRTP cells encoded static eye position. The sensitivity to pursuit eye velocity averaged 0.81 spikes/s per °/s, whereas the average sensitivity to pursuit eye acceleration was 0.20 spikes/s per °/s2. Of the eye-velocity cells with horizontal preferences for pursuit responses, 56% were optimally responsive to contraversive smooth-pursuit eye movements and 44% preferred ipsiversive pursuit. For cells with vertical pursuit preferences, 61% preferred upward pursuit and 39% preferred downward pursuit. The direction selectivity was broad with 50% of the maximal response amplitude observed for directions of smooth pursuit up to ±85° away from the optimal direction. The activities of some rNRTP cells were linearly related to eye position with an average sensitivity of 2.1 spikes/s per deg. In some cells, the magnitude of the response during smooth-pursuit eye movements was affected by the position of the eyes even though these cells did not encode eye position. On average, pursuit centered to one side of screen center elicited a response that was 73% of the response amplitude obtained with tracking centered at screen center. For pursuit centered on the opposite side, the average response was 127% of the response obtained at screen center. The results provide a neuronal rationale for the slow, pursuit-like eye movements evoked with rNRTP microstimulation and for the deficits in smooth-pursuit eye movements observed with ibotenic acid injection into rNRTP. More globally, the results support the notion of a frontal and supplementary eye field-rNRTP-cerebellum pathway involved with controlling smooth-pursuit eye movements.
Discharge Dynamics of Oculomotor Neural Integrator Neurons During Conjugate and Disjunctive Saccades and Fixation
Authors: Sylvestre Pierre A. , Choi Julia T. L. , Cullen Kathleen E.
Published: May 2006

Burst-tonic (BT) neurons in the prepositus hypoglossi and adjacent medial vestibular nuclei are important elements of the neural integrator for horizontal eye movements. While the metrics of their discharges have been studied during conjugate saccades (where the eyes rotate with similar dynamics), their role during disjunctive saccades (where the eyes rotate with markedly different dynamics to account for differences in depths between saccadic targets) remains completely unexplored. In this report, we provide the first detailed quantification of the discharge dynamics of BT neurons during conjugate saccades, disjunctive saccades, and disjunctive fixation. We show that these neurons carry both significant eye position and eye velocity-related signals during conjugate saccades as well as smaller, yet important, “slide” and eye acceleration terms. Further, we demonstrate that a majority of BT neurons, during disjunctive fixation and disjunctive saccades, preferentially encode the position and the velocity of a single eye; only few BT neurons equally encode the movements of both eyes (i.e., have conjugate sensitivities). We argue that BT neurons in the nucleus prepositus hypoglossi/medial vestibular nucleus play an important role in the generation of unequal eye movements during disjunctive saccades, and carry appropriate information to shape the saccadic discharges of the abducens nucleus neurons to which they project.
Summation of Forces From Multiple Motor Units in the Cat Soleus Muscle
Authors: Perreault Eric J. , Day Scott J. , Hulliger Manuel , Heckman C. J. , Sandercock Thomas G.
Published: May 2006

Nearly all muscle models and most motor control concepts assume that forces from individual muscle fibers and motor units sum in an additive manner once effects of in-series tendon compliance are taken into account. Due to the numerous mechanical linkages between individual fibers, though, it is unclear whether this assumption is warranted. This work examined motor unit force summation over a wide range of muscle forces in the cat soleus. Nonadditive summation implies a nonlinear summation of motor unit forces. Summation nonlinearities were quantified during interactions of 10 individual motor units and 4 motor unit bundles containing approximately 10 units each. These protocols allowed motor unit force summation to be examined from approximately 0 to 25% of tetanic muscle force. Nonlinear summation was assessed by comparing the actual forces to the algebraic sum of individual units and bundles stimulated in isolation. Superadditive summation meant that the actual force exceeded the algebraic sum, whereas subadditive summation meant that the actual force was smaller than the algebraic sum. Experiments tested the hypothesis that superadditive summation occurs at low force levels when few motor units are recruited, whereas subadditive summation prevails above 10% of tetanic force. Results were consistent with this hypothesis. As in previous studies, nonlinear summation in the soleus was modest, but a clear transition from predominately superadditive to predominantly subadditive summation occurred in the range of 6–8% of tetanic force. The largest nonlinearities were transient and appeared at the onset of recruitment and derecruitment of groups of motor units. The results are discussed in terms of the mechanical properties of the connective tissue forming the tendon and linking muscle fibers.
Inhibitory Component of the Resistance Reflex in the Locomotor Network of the Crayfish
Authors: Le Bon-Jego Morgane , Cattaert Daniel
Published: May 2006

The aim of this study was to investigate the inhibitory components of a resistance reflex in the walking system of the crayfish. This study was performed using an in vitro preparation of several thoracic ganglia including motor nerves and the proprioceptor that codes movements of the second joint (coxo-basipodite chordotonal organ—CBCO). Sinusoidal movements were imposed on the CBCO, and intracellular responses were recorded from levator (Lev) and depressor (Dep) motoneurons (MNs). We found that in MNs that oppose the imposed movements (e.g., the Lev MNs during the imposed downward movement), the response consists in a depolarization resulting from the summation of excitatory postsynaptic potentials (EPSPs). A movement in the opposite direction resulted in hyperpolarization during which inhibitory postsynaptic potentials (IPSPs) summated. The inhibitory pathway to each MN is oligosynaptic (i.e., composed of a small number of neurons in series) and involves spiking interneurons because it was blocked in the presence of a high-divalent cation solution. The IPSPs were mediated by a chloride conductance because their amplitude was sensitive to the chloride concentration of the bathing solution and because they were blocked by the chloride channel blocker, picrotoxin. Resistance reflex IPSPs related to single CBCO neurons could be identified. These unitary IPSPs were blocked in the presence of 3-mercapto-propionic acid, an inhibitor of gamma-amino-butyric acid (GABA) synthesis, indicating that they are mediated by GABA. In addition to this GABAergic pathway, electrical stimulation of the CBCO sensory nerve induced compound IPSPs that were blocked by glutamate pyruvate transaminase (GPT), indicating the presence of glutamatergic inhibitory pathways. These glutamatergic interneurons do not appear to be involved in the resistance reflex, however, as GPT did not block the unitary IPSPs. Functionally, the resistance reflex is mainly supported by movement-coding CBCO sensory neurons. We demonstrate that such movement-coding CBCO neurons produce both monosynaptic EPSPs in the MNs opposing imposed movements and oligosynaptic IPSPs in the antagonistic motoneurons. These results highlight the similarities between the inhibitory pathways in resistance reflex of the crayfish and in the stretch reflex of vertebrates mediated by Ia inhibitory interneurons.
Progesterone Withdrawal Reduces Paired-Pulse Inhibition in Rat Hippocampus: Dependence on GABAAReceptor α4 Subunit Upregulation
Authors: Hsu Fu-Chun , Smith Sheryl S.
Published: May 2006

Withdrawal from the endogenous steroid progesterone (P) after chronic administration increases anxiety and seizure susceptibility via declining levels of its potent GABA-modulatory metabolite 3α-OH-5α-pregnan-20-one (3α,5αTHP). This 3α,5α-THP withdrawal also results in a decreased decay time constant for GABA-gated current assessed using whole cell patch-clamp techniques on pyramidal cells acutely dissociated from CA1 hippocampus. The purpose of this study was to test the hypothesis that the decreases in total integrated GABA-gated current observed at the level of the isolated pyramidal cell would be manifested as a reduced GABA inhibition at the circuit level following hormone withdrawal. Toward this end, adult, female rats were administered P via subcutaneous capsule for 3 wk using a multiple withdrawal paradigm. We then evaluated paired-pulse inhibition (PPI) of pyramidal neurons in CA1 hippocampus using extracellular recording techniques in hippocampal slices from rats 24 h after removal of the capsule (P withdrawal, P Wd). The population spike (PS) was recorded at the stratum pyramidale following homosynaptic orthodromic stimulation in the nearby stratum radiatum. The threshold for eliciting a response was decreased after P Wd, and the mean PS amplitude was significantly increased compared with control values at this time. Paired pulses with 10-ms inter-pulse intervals were then applied across an intensity range from 2 to 20 times threshold. Evaluation of paired-pulse responses showed a significant 40–50% reduction in PPI for PS recorded in the hippocampal CA1 region after P Wd, suggesting an increase in circuit excitability. At this time, enhancement of PPI by the benzodiazepine lorazepam (LZM; 10 μM) was prevented, while pentobarbital (10 μM) potentiation of PPI was comparable to control levels of response. These data are consistent with upregulation of the α4 subunit of the GABAAreceptor (GABAR) as we have previously shown. Moreover, the reduced PPI caused by P Wd was prevented by suppression of GABAR α4-subunit expression following intraventricular administration of specific antisense oligonucleotides (1 μg/h for 72 h). These results demonstrating a reduction in PPI following P Wd suggest that GABAergic-mediated recurrent or feed-forward inhibition occurring at the circuit level were decreased following P Wd in female rats, an effect at least partially attributable to alterations in the GABAR subunit gene expression.
Sustained Muscle Contractions Maintained by Autonomous Neuronal Activity Within the Human Spinal Cord
Authors: Nozaki Daichi , Kawashima Noritaka , Aramaki Yu , Akai Masami , Nakazawa Kimitaka , Nakajima Yasoichi , Yano Hideo
Published: May 2006

It is well known that muscle contraction can be easily evoked in the human soleus muscle by applying single-pulse electrical stimulation to the tibial nerve at the popliteal fossa. We herein reveal the unexpected phenomenon of muscle contractions that can be observed when train stimulation is used instead. We found, in 11 human subjects, that transient electrical train stimulation (1-ms pulses, 50 Hz, 2 s) was able to induce sustained muscle contractions in the soleus muscle that outlasted the stimulation period for greater than 1 min. Subjects were unaware of their own muscle activity, suggesting that this is an involuntary muscle contraction. In fact, the excitability of the primary motor cortex (M1) with the sustained muscle contractions evaluated by transcranial magnetic stimulation was lower than the excitability with voluntary muscle contractions even when both muscle contraction levels were matched. This finding indicates that M1 was less involved in maintaining the muscle contractions. Furthermore, the muscle contractions did not come from spontaneous activity of muscle fibers or from reverberating activity within closed neuronal circuits involving motoneurons. These conclusions were made based on the respective evidence: 1) the electromyographic activity was inhibited by stimulation of the common peroneal nerve that has inhibitory connections to the soleus motoneuron pool and 2) it was not abolished after stopping the reverberation (if any) for approximately 100 ms by inducing the silent period that followed an H-reflex. These findings indicate that the sustained muscle contractions induced in this study are most likely to be maintained by autonomous activity of motoneurons and/or interneurons within the human spinal cord.
PI3-Kinase Inhibitors Abolish the Enhanced Chronotropic Effects of Angiotensin II in Spontaneously Hypertensive Rat Brain Neurons
Authors: Sun Chengwen , Du Jianqing , Sumners Colin , Raizada Mohan K.
Published: May 2006

Angiotensin II (Ang II), acting at Ang II type 1 receptors (AT1Rs), increases the firing rate of neurons from Wistar-Kyoto (WKY) rat brain via protein kinase C (PKC)- and calcium-calmodulin kinase II (CaMKII)-dependent mechanisms. The objectives of this study were twofold; first, to compare the Ang-II-stimulated increase in firing of neurons from WKY and spontaneous hypertensive rats (SHR) and second, to elucidate the signaling mechanisms involved. Action potentials were measured in neurons cultured from SHR and WKY rat brains using the whole cell configuration of the patch-clamp technique in the current-clamp mode. Ang II (100 nM) caused three- and sixfold increases in neuronal firing rate in WKY rat and SHR neurons, respectively; effects that were abolished by the AT1R antagonist Losartan (1 μM). Co-administration of calphostin C (10 μM, a PKC inhibitor) and KN-93 (10 μM, a CaMKII inhibitor) completely blocked this Ang II action in WKY rat neurons, while they caused only a ∼50% attenuation in SHR neurons. The residual increase in firing rate produced by Ang II in SHR neurons was blocked by inhibitors of phosphatidylinositol 3 kinase (PI3-kinase), either LY 294002 (10 μM) or wortmannin (100 nM). These observations suggest that a PI3-kinase signaling pathway may be responsible for the enhanced chronotropic effect produced by Ang II in SHR neurons.
GABA Transporter-1 (GAT1)-Deficient Mice: Differential Tonic Activation of GABAAVersus GABABReceptors in the Hippocampus
Authors: Jensen Kimmo , Chiu Chi-Sung , Sokolova Irina , Lester Henry A. , Mody Istvan
Published: May 2006

After its release from interneurons in the CNS, the major inhibitory neurotransmitter GABA is taken up by GABA transporters (GATs). The predominant neuronal GABA transporter GAT1 is localized in GABAergic axons and nerve terminals, where it is thought to influence GABAergic synaptic transmission, but the details of this regulation are unclear. To address this issue, we have generated a strain of GAT1-deficient mice. We observed a large increase in a tonic postsynaptic hippocampal GABAAreceptor-mediated conductance. There was little or no change in the waveform or amplitude of spontaneous inhibitory postsynaptic currents (IPSCs) or miniature IPSCs. In contrast, the frequency of quantal GABA release was one-third of wild type (WT), although the densities of GABAAreceptors, GABABreceptors, glutamic acid decarboxylase 65 kDa, and vesicular GAT were unaltered. The GAT1-deficient mice lacked a presynaptic GABABreceptor tone, present in WT mice, which reduces the frequency of spontaneous IPSCs. We conclude that GAT1 deficiency leads to enhanced extracellular GABA levels resulting in an overactivation of GABAAreceptors responsible for a postsynaptic tonic conductance. Chronically elevated GABA levels also downregulate phasic GABA release and reduce presynaptic signaling via GABABreceptors thus causing an enhanced tonic and a diminished phasic inhibition.
Cannabinoid Receptor Activation Differentially Modulates Ion Channels in Photoreceptors of the Tiger Salamander
Authors: Straiker Alex , Sullivan Jane M.
Published: May 2006

Cannabinoid CB1 receptors have been detected in retinas of numerous species, with prominent labeling in photoreceptor terminals of the chick and monkey. CB1 labeling is well-conserved across species, suggesting that CB1 receptors might also be present in photoreceptors of the tiger salamander. Synaptic transmission in vertebrate photoreceptors is mediated by L-type calcium currents—currents that are modulated by CB1 receptors in bipolar cells of the tiger salamander. Presence of CB1 receptors in photoreceptor terminals would therefore be consistent with presynaptic modulation of synaptic transmission, a role seen for cannabinoids in other parts of the brain. Here we report immunohistochemical and electrophysiological evidence for the presence of functional CB1 receptors in rod and cone photoreceptors of the tiger salamander. The cannabinoid receptor agonist WIN 55212-2 enhances calcium currents of rod photoreceptors by 39% but decreases calcium currents of large single cones by 50%. In addition, WIN 55212-2 suppresses potassium currents of rods and large single cones by 44 and 48%, respectively. Thus functional CB1 receptors, present in the terminals of rod and cone photoreceptors, differentially modulate calcium and potassium currents in rods and large single cones. CB1 receptors are therefore well positioned to modulate neurotransmitter release at the first synapse of the visual system.
Serotonin Reduces the Hyperpolarization-Activated Current (Ih) in Ventral Tegmental Area Dopamine Neurons: Involvement of 5-HT2Receptors and Protein Kinase C
Authors: Liu Zhaoping , Bunney E. Bradshaw , Appel Sarah B. , Brodie Mark S.
Published: May 2006

Dopaminergic neurons of the ventral tegmental area (VTA) have been implicated in the rewarding properties of drugs of abuse and in the etiology of schizophrenia; serotonin modulation of these neurons may play a role in these phenomena. Whole cell patch-in-the-slice recording in rat brain slices was used to investigate modulation of the hyperpolarization-activated cationic current Ihby serotonin in these neurons. Serotonin (50-500 μM) reduced the amplitude of Ihin a concentration-dependent manner; this effect was reversible after prolonged washout of serotonin. This effect was mimicked by the 5-HT2agonist α-methylserotonin (25 μM) and reversed by the 5-HT2antagonist ketanserin (25 μM). Serotonin reduced the maximal Ihcurrent and conductance (measured at -130 mV) and caused a negative shift in the voltage dependence of Ihactivation. The serotonin-induced reduction in Ihamplitude was antagonized by intracellular administration of the nonspecific protein kinase inhibitor H-7 (75 μM) and the selective protein kinase C inhibitor chelerythrine (25 μM). The protein kinase C activator phorbol 12, 13 diacetate (PDA, 2 μM) reduced Ihamplitude; when PDA and serotonin were applied together, the effect on Ihwas less than additive. These data support the conclusion that serotonin reduces Ihin dopaminergic VTA neurons by acting at serotonin 5-HT2receptors, which activate protein kinase C. This reduction of Ihmay be physiologically important, as the selective inhibitor of Ih, ZD7288, significantly increased dopamine inhibition of firing rate of dopaminergic VTA neurons, an effect that we previously demonstrated with serotonin.
Vestibular Contributions to Gaze Stability During Transient Forward and Backward Motion
Authors: Hess Bernhard J. M. , Angelaki Dora E.
Published: May 2006

The accuracy with which the vestibular system anticipates and compensates for the visual consequences of translation during forward and backward movements was investigated with transient motion profiles in rhesus monkeys trained to fixate targets on an isovergence screen. Early during motion when visuomotor reflexes remain relatively ineffective and vestibular-driven mechanisms have an important role for controlling the movement of the eyes, a large asymmetry was observed for forward and backward heading directions. During forward motion, ocular velocity gains increased steeply and reached near unity gains as early as 40–50 ms after motion onset. In addition, instantaneous directional errors also remained <10° for forward headings. In contrast, backward motion was characterized by smaller vestibular gains and larger directional errors during the first 70 ms of the movement. To evaluate the accumulated retinal slip and vergence errors during the early epochs of motion when vestibular-driven mechanisms dominate gaze stability, the movement of a virtual fixation point defined by the intersection of the two gaze lines was quantitatively compared with the respective movement of the extinguished target in head coordinates. Both conjugate retinal slip and vergence errors were <0.2° during the first 70 ms of the movement, with forward motion conjugate errors typically being smaller as compared with backward motion directions. Thus vestibularly driven gaze stabilization mechanisms can effectively minimize conjugate retinal slip errors as well as keep binocular disparity errors low during the open loop interval of head movement.
Characterization of Cutaneous Primary Afferent Fibers Excited by Acetic Acid in a Model of Nociception in Frogs
Authors: Hamamoto Darryl T. , Simone Donald A.
Published: May 2006

Acetic acid applied to the hind limb of a frog evokes nocifensive behaviors, including a vigorous wiping of the exposed skin, referred to as the wiping response. The aim of this study was to examine the responses of cutaneous primary afferent fibers in frogs to acetic acid (pH 2.84–1.42) applied topically to the skin. Conventional electrophysiological methods were used to record neuronal activity from single identified primary afferent fibers with cutaneous receptive fields on the hind limb. Fibers were classified according to their conduction velocities and responses evoked by mechanical and thermal (heat and cold) stimuli. One hundred and twenty-two mechanosensitive afferent fibers were studied (44 Aβ, 60 Aδ, and 18 C fibers). Thirty-nine percent of all fibers were excited by acetic acid, but a greater percentage of Aδ (52%) and C fibers (44%) were excited than Aβ fibers (20%). Evoked responses of fibers increased with increasingly more acidic pH until the greatest responses were evoked by acetic acid at pH 2.59–2.41. Application of acetic acid at pHs <2.41 evoked less excitation, suggesting that fibers became desensitized. Similar percentages of nociceptors and low-threshold mechanoreceptors were excited by acetic acid. Thus primary afferent fibers were excited by acetic acid at pHs that have been shown to evoke the wiping response in our previous study. The results of the present study suggest that the model of acetic acid-induced nociception in frogs may be useful for studying the mechanisms by which tissue acidosis produces pain.
Evidence for Functionally Distinct Synaptic NMDA Receptors in Ventromedial Versus Dorsolateral Striatum
Authors: Chapman David E. , Keefe Kristen A. , Wilcox Karen S.
Published: May 2006

N-methyl-d-aspartate receptors (NMDARs) are comprised of different subunits. NR2 subunits confer different pharmacological and biophysical properties to NMDARs. Although NR2B subunit expression is uniform throughout striatum, NR2A subunit expression is greater laterally. Pharmacologically isolated NMDAR-mediated excitatory postsynaptic currents (NMDAR-EPSCs) were elicited using minimal local stimulation and recorded in the whole cell configuration to test the hypothesis that biophysical and pharmacological properties of NMDAR-EPSCs of striatal neurons would vary as a function of their location in adult rat striatum. We observed that the decay-time kinetics of NMDAR-EPSCs are significantly slower in neurons of ventromedial versus dorsolateral striatum. Whereas ifenprodil did not differentially affect NMDAR-EPSCs in these regions, application of either glycine or d-serine increased the peak current of NMDAR-EPSCs selectively in dorsolateral striatum. These data provide evidence for functionally distinct NMDARs in the same neuron type in the same brain region of the adult rodent brain. These data thus suggest that the nature of synaptic processing of excitatory input is different in the ventromedial and dorsolateral striatum of the adult rodent brain, regions differentially involved in limbic versus sensorimotor processes, respectively.
Stretch Sensitivity of Cutaneous RA Mechanoreceptors in Rat Hairy Skin
Authors: Robichaud Daniel R. , Del Prete Zaccaria , Grigg Peter
Published: May 2006

Twenty-five rapidly adapting mechanoreceptor afferents were recorded in an in vitro preparation of rat skin and nerve. Single units were recorded while the skin was subjected to dynamic uniaxial stretch using a pseudo-Gaussian noise (PGN) input waveform. Force was the controlled variable in stretch stimuli. Measured loads and displacements were used to calculate tensile stresses, strains, and their rates of change. Associations between spike responses and individual stimulus components such as tensile stress or strain were determined in a reverse correlation design using multiple logistic regression. Spikes were strongly associated with stress, at memory times from 0 to 14 ms, and with the rate of change of stress, at a memory times between 6 and 18 ms. There was a strong interaction between stress and its rate of change, with a maximum value at a memory time of 10 ms. We found no relationship between spike responses and strain.
Motor Scaling By Viewing Distance of Early Visual Motion Signals During Smooth Pursuit
Authors: Zhou Hui-Hui , Wei Min , Angelaki Dora E.
Published: May 2006

The geometry of gaze stabilization during head translation requires eye movements to scale proportionally to the inverse of target distance. Such a scaling has indeed been demonstrated to exist for the translational vestibuloocular reflex (TVOR), as well as optic flow–selective translational visuomotor reflexes (e.g., ocular following, OFR). The similarities in this scaling by a neural estimate of target distance for both the TVOR and the OFR have been interpreted to suggest that the two reflexes share common premotor processing. Because the neural substrates of OFR are partly shared by those for the generation of pursuit eye movements, we wanted to know if the site of gain modulation for TVOR and OFR is also part of a major pathway for pursuit. Thus, in the present studies, we investigated in rhesus monkeys whether initial eye velocity and acceleration during the open-loop portion of step ramp pursuit scales with target distance. Specifically, with visual motion identical on the retina during tracking at different distances (12, 24, and 60 cm), we compared the first 80 ms of horizontal pursuit. We report that initial eye velocity and acceleration exhibits either no or a very small dependence on vergence angle that is at least an order of magnitude less than the corresponding dependence of the TVOR and OFR. The results suggest that the neural substrates for motor scaling by target distance remain largely distinct from the main pathway for pursuit.
Dynamic Recording of Cell Death in the In Vitro Dorsal Vagal Nucleus of Rats in Response to Metabolic Arrest
Authors: Müller Michael , Ballanyi Klaus
Published: May 2006

Anoxic/ischemic neuronal death is usually assessed in cell cultures or in vivo within a time window of 24 h to several days using the nucleic acid stain propidium iodide or histological techniques. Accordingly, there is limited information on the time course of such neuronal death. We loaded acute rat brain stem slices with propidium iodide for dynamic fluorometric recording of metabolic arrest-related cell death in the dorsal vagal nucleus. This model was chosen because dorsal vagal neurons show a graded response to metabolic inhibition: anoxia and aglycemia cause a sustained hyperpolarization, whereas ischemia induces a glutamate-mediated, irreversible depolarization. We found that the number of propidium iodide–labeled cells increased from 27% to 43% of total cell count within 1–7 h after preparation of slices. Compared with these untreated control slices, cyanide-induced anoxia (30 min) or aglycemia (1 h) did not cause further cell death, whereas 3-h aglycemia destroyed an additional 13% of cells. Ischemia (1 h) due to cyanide plus iodoacetate immediately labeled an additional 20% of cells, and an additional 48% of cells were destroyed within the following 3 h of postischemia. Continuous recording of propidium iodide fluorescence showed that loss of membrane integrity started within 25 min after onset of the ischemic depolarization and the concomitant intracellular Ca2+rise. The results show that propidium iodide can be used to monitor cell death in acute brain slices. Our findings suggest that pronounced cell death occurs within a period of 1–4 h after onset of metabolic arrest and is apparently due to necrotic/oncotic mechanisms.
Task-Dependent Modulation of Multi-Digit Force Coordination Patterns
Authors: Rearick Matthew P. , Casares Amparo , Santello Marco
Published: May 2006

When grasping and holding an object with five digits under a variety of task constraints, subjects use well-defined force coordination patterns, i.e., consistent force covariations and in-phase synchronization among all digit pairs. The question arises as to whether these force coordination patterns are default mechanisms for controlling multi-digit force production or whether they are specific to lifting and holding an object. To address this question, we asked subjects to grasp a manipulandum and exert forces with five digits simultaneously so as to match a force template measured from an actual object grasp, lift, and hold task (GLH). Unlike GLH, the force production task (FP) lacked the constraint of having to maintain object stability against gravity. The amplitude of individual finger forces and force covariations were similar for both tasks (with the exception of the little finger, which tended to produce less force in FP). Nonetheless, when multiple grip forces were not required to hold the manipulandum against gravity (FP), there was a significantly lower tendency for forces to be synchronized with higher intertrial variability of phase differences between forces exerted by all digit-pairs. Furthermore, the tendency for force phase differences to cluster at 0° was lower for FP than GLH. These results suggest that some aspects of the control of multi-digit grasping, i.e., force synchronization, are specific to object lift and hold rather than to the production of multi-digit forces. Modeling work suggests that motor unit synchronization might play an important role in the modulation of force synchronization patterns.
Local Field Potentials and the Encoding of Whisker Deflections by Population Firing Synchrony in Thalamic Barreloids
Authors: Temereanca Simona , Simons Daniel J.
Published: May 2006

In layer IV of rat somatosensory cortex, barrel circuitry is highly sensitive to thalamic population firing rates during the first few milliseconds of the whisker-evoked response. This sensitivity of barrel neurons to thalamic firing synchrony was inferred previously from analysis of simulated barrel circuitry and from single-unit recordings performed one at a time. In this study, we investigate stimulus-dependent synchronous activity in the thalamic ventral posteromedial nucleus (VPm) using the more direct approach of local field potential (LFP) recording. We report that thalamic barreloid neurons generate larger magnitude LFP responses to principal versus adjacent whiskers, to preferred versus nonpreferred movement directions, and to high- versus low-velocity/acceleration deflections. Responses were better predicted by acceleration than velocity, and they were insensitive to the final amplitude of whisker deflection. Importantly, reliable and robust stimulus/response relationships were found only for the initial 1.2–7.5 ms of the thalamic LFP response, reflecting arrival of afferent information from the brain stem. Later components of the thalamic response, which are likely to coincide with arrival of inhibitory inputs from the thalamic reticular nucleus and excitatory inputs from the barrel cortex itself, are variable and poorly predicted by stimulus parameters. Together with previous results, these findings underscore a critical role for thalamic firing synchrony in the encoding of small but rapidly changing perturbations of specific whiskers in particular directions.
Loss of αCGRP Reduces Sound-Evoked Activity in the Cochlear Nerve
Authors: Maison Stéphane F. , Emeson Ronald B. , Adams Joe C. , Luebke Anne E. , Liberman M. Charles
Published: May 2006

α-Calcitonin gene-related peptide (αCGRP) is one of several neurotransmitters immunolocalized in the unmyelinated component of the cochlear efferent innervation, the lateral olivocochlear (OC) system, which makes axo-dendritic synapses with cochlear sensory neurons. In rodents, CGRP is also immunocolocalized in the myelinated medial OC system, which contacts cochlear outer hair cells (OHCs). To understand the role(s) of this neuropeptide in the OC system, we characterized the auditory phenotype of αCGRP-null mice. Cochlear threshold sensitivity was normal in mutant mice, both via a neural metric, the auditory brain stem response (ABR), and an OHC-based metric, distortion product otoacoustic emissions (DPOAEs). Medial OC function and resistance to acoustic injury were also unaffected by αCGRP deletion: the former was assessed by measuring cochlear response suppression with electrical stimulation of the OC bundle, the latter by measuring temporary threshold shifts after exposure to high level sound. However, significant abnormality in αCGRP-null mice was seen in the growth of cochlear neural responses with increasing stimulus level. This observation, contrasted with normal amplitude-versus-level functions for DPOAEs, is consistent with a selective, postsynaptic effect on cochlear neurons via αCGRP release from lateral OC terminals. This constitutes the most direct evidence to date for a functional role of the lateral OC system in the auditory periphery.
Benzodiazepines Block α2-Containing Inhibitory Glycine Receptors in Embryonic Mouse Hippocampal Neurons
Authors: Thio Liu Lin , Shanmugam Ananth , Isenberg Keith , Yamada Kelvin
Published: May 2006

Inhibitory glycine receptors (GlyRs) in the mammalian cortex probably contribute to brain development and to maintaining tonic inhibition. Given their presence throughout the cortex, their modulation likely has important physiological consequences. Although benzodiazepines potentiate γ-aminobutyric acidAreceptors (GABAARs), they may also modulate GlyRs because binding studies initially suggested that they act at GlyRs. Furthermore, their diminished ability to potentiate neonatal GABAARs suggests that they may exert their beneficial clinical effects at another site in the developing brain. Therefore we examined the effect of benzodiazepines on whole cell currents mediated by GlyRs in cultured embryonic mouse hippocampal neurons. First, we determined the GlyR subunit composition in this preparation. Glycine, β-alanine, and taurine activate strychnine-sensitive chloride currents in a dose-dependent manner. Maximal concentrations of the three agonists produce equal, nonadditive responses as expected of full agonists. The pharmacological properties of the GlyR currents including their pattern of modulation by picrotoxinin, picrotin, and tropisetron indicate that GlyRs consist of α2β heteromers and α2homomers. Reverse transcriptase polymerase chain reaction (RTPCR) studies confirmed the presence of α2and β subunits. Second, we found that micromolar concentrations of some benzodiazepines, including chlordiazepoxide and nitrazepam, inhibit GlyR currents. Nitrazepam inhibition of GlyRs is noncompetitive, is not voltage dependent, and does not reflect enhanced desensitization. Thus benzodiazepines allosterically inhibit α2-containing GlyRs in embryonic mouse hippocampal neurons via a “low”-affinity site.
Ethanol Dual Modulatory Actions on Spontaneous Postsynaptic Currents in Spinal Motoneurons
Authors: Ziskind-Conhaim Lea , Gao Bao-Xi , Hinckley Christopher
Published: May 2006

Recently we have shown that acute ethanol (EtOH) exposure suppresses dorsal root-evoked synaptic potentials in spinal motoneurons. To examine the synaptic mechanisms underlying the reduced excitatory activity, EtOH actions on properties of action potential-independent miniature excitatory and inhibitory postsynaptic currents (mEPSCs and mIPSCs) were studied in spinal motoneurons of newborn rats. Properties of mEPSCs generated by activation of N-methyl-d-aspartate receptors (NMDARs) and non-NMDA receptors and of mIPSCs mediated by glycine and γ-aminobutyric acid-A receptors (GlyR and GABAAR) were examined during acute exposure to 70 and 200 mM EtOH. In the presence of 70 mM EtOH, the frequency of NMDAR- and non-NMDAR-mediated mEPSCs decreased to 53 ± 5 and 45 ± 7% (means ± SE) of control values, respectively. In contrast, the frequency of GlyR- and GABAAR-mediated mIPSCs increased to 138 ± 15 and 167 ± 23% of control, respectively. Based on the quantal theory of transmitter release, changes in the frequency of miniature currents are correlated with changes in transmitter release, suggesting that EtOH decreased presynaptic glutamate release and increased the release of both glycine and GABA. EtOH did not change the amplitude or rise and decay times of either mEPSCs or mIPSCs, indicating that the presynaptic changes were not associated with changes in the properties of postsynaptic receptors/channels. Acute exposure to 200 mM EtOH increased mIPSC frequency two- to threefold, significantly higher than the increase induced by 70 mM EtOH. However, the decrease in mEPSC frequency was similar to that observed in 70 mM EtOH. Those findings implied that the regulatory effect of EtOH on glycine and GABA release was dose-dependent. Exposure to the higher EtOH concentration had opposite actions on mEPSC and mIPSC amplitudes: it attenuated the amplitude of NMDAR- and non-NMDAR-mediated mEPSCs to ∼80% of control and increased GlyR- and GABAAR-mediated mIPSC amplitude by ∼20%. EtOH-induced changes in the amplitude of postsynaptic currents were not associated with changes in their basic kinetic properties. Our data suggested that in spinal networks of newborn rats, EtOH was more effective in modulating the release of excitatory and inhibitory neurotransmitters than changing the properties of their receptors/channels.
Baseline Glutamate Levels Affect Group I and II mGluRs in Layer V Pyramidal Neurons of Rat Sensorimotor Cortex
Authors: Bandrowski A. E. , Huguenard J. R. , Prince D. A.
Published: May 2006

Possible functional roles for glutamate that is detectable at low concentrations in the extracellular space of intact brain and brain slices have not been explored. To determine whether this endogenous glutamate acts on metabotropic glutamate receptors (mGluRs), we obtained whole cell recordings from layer V pyramidal neurons of rat sensorimotor cortical slices. Blockade of mGluRs with (+)-α-amino-4-carboxy-α-methyl-benzeacetic acid (MCPG, a general mGluR antagonist) increased the mean amplitude of spontaneous excitatory postsynaptic currents (sEPSCs), an effect attributable to a selective increase in the occurrence of large amplitude sEPSCs. 2S-2-amino-2-(1S,2S-2-carboxycyclopropyl-1-yl)-3-(xanth-9-yl)propanoic acid (LY341495, a group II antagonist) increased, but R(−)-1-amino-2,3-dihydro-1H-indene-1,5-dicarboxylic acid (AIDA) and (RS)-hexyl-HIBO (group I antagonists) decreased sEPSC amplitude, and (R,S)-α-cyclopropyl-4-phosphonophenylglycine (CPPG, a group III antagonist) did not change it. The change in sEPSCs elicited by MCPG, AIDA, and LY341495 was absent in tetrodotoxin, suggesting that it was action potential-dependent. The increase in sEPSCs persisted in GABA receptor antagonists, indicating that it was not due to effects on inhibitory interneurons. AIDA and ( S)-3,5-dihydroxyphenylglycine (DHPG, a group I agonist) elicited positive and negative shifts in holding current, respectively. LY341495 and (2S,2′R,3′R)-2-(2′,3′-dicarboxycyclopropyl)glycine (DCG-IV, a group II agonist) elicited negative and positive shifts in holding current, respectively. The AIDA and LY341495 elicited currents persisted in TTX. Finally, in current clamp, LY341495 depolarized cells by ∼2 mV and increased the number of action potentials to a given depolarizing current pulse. Thus ambient levels of glutamate tonically activate mGluRs and regulate cortical excitability.
Somatotopic Organization of the Lateral Part of Area F2 (Dorsal Premotor Cortex) of the Macaque Monkey
Authors: Raos Vassilis , Franchi Gianfranco , Gallese Vittorio , Fogassi Leonardo
Published: May 2006

The somatotopy of the lateral part of dorsal premotor area F2 has been studied by means of intracortical microstimulation and single neuron recording. The results show that most of this sector of F2 is excitable with low-intensity currents (3–40 μA) and that intracortical microstimulation evokes forelimb and trunk movements. Both proximal and distal forelimb movements are evoked in similar percentages. The proximal and distal forelimb representations partially overlap. However, proximal movements tend to be located more medially (laterally to the superior precentral dimple), whereas distal movements tend to be located more laterally (medially to the spur of the arcuate sulcus). The somatotopic organization demonstrated with microstimulation is confirmed by the similar somatotopic organization of active movements and of somatosensory properties revealed by single-neuron recording. The excitability and somatotopic organization of the lateral part of area F2 are discussed in relation to previous electrophysiological and anatomical findings. The involvement of the distal forelimb representation of area F2 in programming and controlling reaching to grasp movements is suggested.
Nature and Interaction of Signals From the Receptive Field Center and Surround in Macaque V1 Neurons
Authors: Cavanaugh James R. , Bair Wyeth , Movshon J. Anthony
Published: May 2006

Information is integrated across the visual field to transform local features into a global percept. We now know that V1 neurons provide more spatial integration than originally thought due to the existence of their nonclassical inhibitory surrounds. To understand spatial integration in the visual cortex, we have studied the nature and extent of center and surround influences on neuronal response. We used drifting sinusoidal gratings in circular and annular apertures to estimate the sizes of the receptive field's excitatory center and suppressive surround. We used combinations of stimuli inside and outside the receptive field to explore the nature of the surround influence on the receptive field center as a function of the relative and absolute contrast of stimuli in the two regions. We conclude that the interaction is best explained as a divisive modulation of response gain by signals from the surround. We then develop a receptive field model based on the ratio of signals from Gaussian-shaped center and surround mechanisms. We show that this model can account well for the variations in receptive field size with contrast that we and others have observed and for variations in size with the state of contrast adaptation. The model achieves this success by simple variations in the relative gain of the two component mechanisms of the receptive field. This model thus offers a parsimonious explanation of a variety of phenomena involving changes in apparent receptive field size and accounts for these phenomena purely in terms of two receptive field mechanisms that do not themselves change in size. We used the extent of the center mechanism in our model as an indicator of the spatial extent of the central excitatory portion of the receptive field. We compared the extent of the center to measurements of horizontal connections within V1 and determined that horizontal intracortical connections are well matched in extent to the receptive field center mechanism. Input to the suppressive surround may come in part from feedback signals from higher areas.
Capacity of Vertical VOR Adaptation in Squirrel Monkey
Authors: Hirata Y. , Lockard J. M. , Highstein S. M.
Published: May 2006

Squirrel monkeys were trained using newly developed visual-vestibular mismatch paradigms to test the asymmetrical simultaneous induction of vertical vestibuloocular reflex (VOR) gain changes in opposite directions (high and low) either in the upward and downward directions or in response to high- and low-frequency stimuli. The first paradigm consists of sinusoidal head movement [ Asin(ω t)] and a full rectified sinusoidal optokinetic stimulus [±‖ A sin(ω t)‖], whereas the second paradigm consists of the sum of two sinusoids with different frequencies { A sin(ω1 t) + A sin(ω2 t) for head motion and ±[ Asin(ω1 t) − Asin(ω2 t)] for the optokinetic stimulus, ω1 = 0.1π, ω2 = 5π}. The first paradigm induced a half rectified sinusoidal eye-velocity trace, i.e., suppression of the VOR during upward head motion and enhancement during downward head motion or vise versa, whereas the second paradigm induced suppression of the VOR at the low-frequency ω1 and enhancement at the high-frequency ω2 or vise versa. After 4 h of exposure to these paradigms, VOR gains of up and down or high and low frequency were modified in opposite directions. We conclude that the monkey vertical VOR system is capable of up-down directionally differential adaptation as well as high-low frequency differential adaptation. However, experiments also suggest that these gain controls are not completely independent because the magnitudes of the gain changes during simultaneous asymmetrical training were less than those achieved by symmetrical training or training in only one of the two components, indicating an influence of the gain controls on each other. These results confine the adaptive site(s) responsible for vertical VOR motor learning to those that can process up and downward or low- and high-frequency head signal separately but not completely independently.
Relating Network Synaptic Connectivity and Network Activity in the Lobster (Panulirus interruptus) Pyloric Network
Authors: Weaver Adam L. , Hooper Scott L.
Published: May 2006

The lobster pyloric network has a densely interconnected synaptic connectivity pattern, and the role individual synapses play in generating network activity is consequently difficult to discern. We examined this issue by quantifying the effect on pyloric network phasing and spiking activity of removing the Lateral Pyloric (LP) and Ventricular Dilator (VD) neurons, which synapse onto almost all pyloric neurons. A confounding factor in this work is that LP and VD neuron removal alters pyloric cycle period. To determine the effects of LP and VD neuron removal on pyloric activity independent of these period alterations, we altered network period by current injection into a pyloric pacemaker neuron, hyperpolarized the LP or VD neuron to functionally remove each from the network, and plotted various measures of pyloric neuron activity against period with and without the LP or VD neuron. In normal physiological saline, in many (or most) cases removing either neuron had surprisingly little effect on the activity of its postsynaptic partners, which suggests that under these conditions these neurons play a relatively small role in determining pyloric activity. In the cases in which removal did alter postsynaptic activity, the effects were inconsistent across preparations, which suggests that either despite producing very similar neural outputs, pyloric networks from different animals have different cellular and synaptic properties, or some synapses contribute to network activity only under certain modulatory conditions, and the “baseline” level of modulatory influence the network receives from higher centers varies from animal to animal.