bluuebunny/crossref_metadata_2025_split huggingface dataset:
Coordinate System for Learning in the Smooth Pursuit Eye Movements of Monkeys
Authors: Kahlon Maninder , Lisberger Stephen G. 
Published: April 2018

Learning was induced in smooth pursuit eye movements by repeated presentation of targets that moved at one speed for 100 msec and then changed to a second, higher or lower, speed. The learned changes, measured as eye acceleration for the first 100 msec of pursuit, were largest in a “late” interval from 50 to 80 msec after the onset of pursuit and were smaller and less consistent in the earliest 30 msec of pursuit. In each experiment, target motion in one direction consisted of learning trials, whereas target motion in the opposite (control) direction consisted of trials in which targets moved at a constant speed for the entire duration of the trial. Under these conditions, the learning did not generalize to the control direction. For target motion in the learning direction, the changes in pursuit generalized to responses evoked by targets moving at speeds ranging from 15 to 45°/sec as well as to targets of different colors and sizes. Although learning was induced at the initiation of pursuit, it generalized to the response to image motion in the learning direction when it was presented during pursuit in the learning direction. However, learning did not generalize to the response to image motion in the learning direction when it was presented during pursuit in the control direction. The results suggest that the learning does not occur in purely sensory or motor coordinates but in an intermediate reference frame at least partly defined by the direction of eye movement. The selectivity of learning provides new evidence for a previously hypothesized neural “switch” that gates visual information on the basis of movement direction. This selectivity also suggests that the locus of pursuit learning is in pathways related to the operation of the switch.
The Sympathetic Nervous System Contributes to Capsaicin-Evoked Mechanical Allodynia But Not Pinprick Hyperalgesia in Humans
Authors: Liu Maywin , Max Mitchell B. , Parada Suzan , Rowan Janet S. , Bennett Gary J. 
Published: April 2018

The contribution of the sympathetic nervous system (SNS) to pain, mechanical allodynia (MA), and hyperalgesia in humans is controversial. A clearer understanding is crucial to guide therapeutic use of sympatholytic surgery, blocks, and drug treatments. In rats, capsaicin-evoked MA, and to some extent, pinprick hyperalgesia (PPH), can be blocked with α-adrenoreceptor antagonists. In this study, we examined the contribution of the SNS to MA and PPH in normal human subjects by blocking α-adrenoreceptors with intravenous phentolamine.In a double-blinded, placebo-controlled, crossover study, subjects were given IV saline or phentolamine, 1 mg/kg over 20 min. Ten minutes after the start of the infusion, subjects received 100 μg of intradermal capsaicin on the foot dorsum with the temperature of the injected site clamped at 36°C. The temperature of the uninjected foot was used to monitor the degree of α-adrenoreceptor blockade produced by phentolamine. Ongoing pain and MA and PPH areas were measured every 5 min for 60 min.A significantly greater increase in temperature on the uninjected foot was seen during the phentolamine infusion compared with the saline infusion, indicating α-adrenergic blockade. Significantly less MA was observed with the phentolamine infusion 10–25 min after capsaicin injection than with the saline infusion. No significant differences in ongoing pain or PPH areas were seen between the two infusions at any time.Our results suggest that capsaicin-evoked MA and PPH have different mechanisms, with the SNS having a role in MA but not in PPH or ongoing pain.
Ionic Currents Underlying Developmental Regulation of Repetitive Firing inAplysiaBag Cell Neurons
Authors: Nick Teresa A. , Kaczmarek Leonard K. , Carew Thomas J. 
Published: April 2018

We have investigated the developmental regulation of the ability to fire repetitively in the bag cell neurons ofAplysia californica, a neuronal system in which the behavioral effects of repetitive firing are well characterized. Adult bag cell neurons exhibit an afterdischarge, consisting of prolonged depolarization and repetitive firing, which causes the release of several peptides from these neurons that induce egg-laying behaviors. Afterdischarge can be triggeredin vitroby a variety of stimuli, including electrical stimulation and exposure to the potassium channel blocker tetraethyl ammonium chloride (TEA). In contrast to adults, juvenile neurons did not exhibit afterdischarge in response to pleural–abdominal connective shock or TEA. Juvenile neurons did exhibit, however, prolonged depolarizations in the presence of TEA, perhaps reflecting the anlage of the mechanism responsible for afterdischarge in the adult.To investigate developmental mechanisms underlying the regulation of repetitive firing, we compared ionic currents in adult and juvenile bag cell neurons. We found that during the period in which these neurons acquire the capacity to fire repetitively, a number of currents are regulated: (1) three K+currents decrease (Ca2+-dependent K+and two components of voltage-dependent delayed-rectifier K+current); (2) A-type K+current increases; and (3) two Ca2+currents increase (basal and PKC-activated). This pattern is consistent with the increase in the ability to fire repetitively that we observe during maturation: our results indicate that developmental control of repetitive firing in this system is accompanied by selective regulation of specific ionic currents which, after maturation, play important roles in generating the afterdischarge and triggering egg-laying behaviors.
Dopamine and Spatial Working Memory in Rats and Monkeys: Pharmacological Reversal of Stress-Induced Impairment
Authors: Murphy Beth L. , Arnsten Amy F. T. , Jentsch J. David , Roth Robert H. 
Published: April 2018

The anxiogenic benzodiazepine inverse agonist FG7142 increases dopamine turnover in rodent prefrontal cortex but not in other dopamine terminal field areas. FG7142-induced increases in prefrontal cortical dopamine receptor stimulation impair prefrontal-dependent, but not nonprefrontal-dependent, cognitive tasks in rats and monkeys. The degree of impairment correlates with levels of prefrontal cortical dopamine turnover in rats and can be blocked in rats and monkeys with dopamine receptor antagonists, suggesting that increased dopamine turnover is directly related to the cognitive deficits.The current study examined nondopaminergic drug effects on FG7142-perturbed biochemistry and cognition. Both the noradrenergic α-2 agonist clonidine and the glycine/NMDA antagonist (+)HA966 prevented the FG7142-induced increase in dopamine turnover in rodent prefrontal cortex. Infusion of (+)HA966 into the ventral tegmental area (VTA) also blocked this increase in dopamine turnover, indicating that critical modulatory effects of (+)HA966 on FG7142-induced changes in dopamine turnover are occurring at the level of mesoprefrontal dopamine neuron cell bodies. Systemic (+)HA966 and clonidine, but not propranolol ord-cycloserine, prevented FG7142-associated spatial working memory deficits in rats and monkeys. These results support the idea of a critical range of dopamine turnover for optimal prefrontal cortical cognitive functioning, with excessive dopamine turnover leading to cognitive impairment. These studies also provide evidence for the regulation of prefrontal cortical dopamine turnover and cognition by multiple neurotransmitter systems and suggest that the VTA is an important regulatory site for these effects.
Differential Regulation of Ciliary Neurotrophic Factor (CNTF) and CNTF Receptor α Expression in Astrocytes and Neurons of the Fascia Dentata after Entorhinal Cortex Lesion
Authors: Lee Mun-Yong , Deller Thomas , Kirsch Matthias , Frotscher Michael , Hofmann Hans-Dieter 
Published: April 2018

Neurotrophic factors have been implicated in reactive processes occurring in response to CNS lesions. Ciliary neurotrophic factor (CNTF), in particular, has been shown to ameliorate axotomy-induced degeneration of CNS neurons and to be upregulated at wound sites in the brain. To investigate a potential role of CNTF in lesion-induced degeneration and reorganization, we have analyzed the expression of CNTF protein and CNTF receptor α (CNTFRα) mRNA in the rat dentate gyrus after unilateral entorhinal cortex lesions (ECLs), using immunocytochemistry and nonradioactivein situhybridization, respectively.In sham-operated as in normal animals, CNTF protein was not detectable by immunocytochemistry. Starting at 3 d after ECL, upregulation of CNTF expression was observed in the ipsilateral outer molecular layer (OML). Expression was maximal at around day 7, and at this stage immunoreactivity could be specifically localized to astrocytes in the ipsilateral OML. By day 14 postlesion, CNTF immunoreactivity had returned to control levels. CNTFRα mRNA was restricted to neurons of the granule cell layer in controls. Three days postlesion, prominent CNTFRα expression was observed in the deafferented OML. A similar but less prominent response was noticed in the contralateral OML. After 10 d, CNTFRα expression had returned to control levels. Double labeling for CNTFRα mRNA and glial fibrillary acidic protein (GFAP) showed that upregulation of CNTFRα occurred in reactive, GFAP-immunopositive astrocytes of the OML. A substantial reduction of CNTFRα expression in the deafferented granule cells was transiently observed at 7 and 10 d postlesion. Our results suggest a paracrine or autocrine function of CNTF in the regulation of astrocytic and neuronal responses after brain injury.
A Monosynaptic GABAergic Input from the Inferior Colliculus to the Medial Geniculate Body in Rat
Authors: Peruzzi Daniel , Bartlett Edward , Smith Philip H. , Oliver Douglas L. 
Published: April 2018

The goal was to investigate possible monosynaptic GABAergic projections from the inferior colliculus (IC) to thalamocortical neurons of the medial geniculate body (MGB) in the rat. Although there is little evidence for such a projection in other sensory thalamic nuclei, a GABAergic, ascending auditory projection was reported recently in the cat. In the present study, immunohistochemical and tract-tracing methods were used to identify neurons in the IC that contain GABA and project to the MGB. GABA-positive projection neurons were most numerous in the central nucleus and less so in the dorsal and lateral cortex. They were rare in the lateral tegmental system and brachium of the IC. The dorsal nucleus of the lateral lemniscus also contained GABA-positive projection neurons. In brain slices, stimulation of the brachium produced monosynaptic inhibitory postsynaptic potentials in morphologically identified thalamocortical relay neurons. The inhibitory potentials cannot originate locally, because they persisted when ionotropic glutamatergic transmission was blocked. Typically, brachium stimulation elicited a GABAA-mediated inhibitory potential followed by an excitatory potential and a longer latency GABAB-mediated inhibitory potential.We conclude that the GABA-containing neurons of the IC make short-latency, monosynaptic inputs to the thalamocortical projection neurons in the MGB. Such inputs may distinguish the main auditory pathway from indirect or tegmental auditory pathways as well as from other sensory systems. Monosynaptic inhibitory inputs to the medial geniculate may be important for the regulation of firing patterns in thalamocortical neurons.
Differential Activation of the Caudate Nucleus in Primates Performing Spatial and Nonspatial Working Memory Tasks
Authors: Levy Richard , Friedman Harriet R. , Davachi Lila , Goldman-Rakic Patricia S. 
Published: April 2018

The caudate nucleus is part of an anatomical network subserving functions associated with the dorsolateral prefrontal cortex (DLPFC). The aim of the present study was to investigate whether the metabolic activity in the striatum reflects specific changes in working memory tasks, which are known to be dependent on the DLPFC, and whether these changes reflect the topographic ordering of prefrontal connections within the striatum. Local cerebral glucose utilization (LCGU) rates were assessed in the striatum by the14C-2-deoxyglucose method in monkeys that performed a spatial (delayed spatial alternation), a nonspatial (delayed object alternation) visual working memory task, or tasks that did not involve working memory, i.e., a visual pattern discrimination or sensorimotor paradigm.The results show a topographic segregation of activation related to spatial and nonspatial working memory, respectively. The delayed spatial alternation task increases LCGU rates bilaterally by 33–43% in the head of the caudate nucleus, where efferents from the dorsolateral prefrontal cortex project most densely. The delayed object alternation task enhances LCGU rates bilaterally by 32–37% in the body of the caudate nucleus, which is innervated by the temporal cortex. The visual pattern discrimination task similarly activated the body of the caudate, but in a smaller region and only in the right hemisphere.These findings provide the first evidence for metabolic activation of the caudate nuclei in working memory, supporting the role of this nucleus as a node in a neural network mediating DLPFC-dependent working memory processes. The double dissociation of activation observed suggests an anatomical and functional segregation of cortico-striatal circuits subserving spatial and nonspatial cognitive operations.
Unilateral Lesions of the Dorsal Striatum in Rats Disrupt Responding in Egocentric Space
Authors: Brasted Peter J. , Humby Trevor , Dunnett Stephen B. , Robbins Trevor W. 
Published: April 2018

Rats were trained in a specially designed, multichoice operant chamber on a visual choice reaction time task designed to assess performance on each side of the rat’s body. The task required animals to sustain a nose poke in a central hole, until a brief light stimulus was presented in either of two holes that were located on the same side of the box. Once the rats were trained to perform the task to both sides independently they received unilateral injections of quinolinic acid into the dorsal striatum.Postoperatively, lesioned animals were impaired when performing the task on the side contralateral to the lesion. The time taken to initiate contralateral responses was increased. Contralateral responses were also exclusively biased toward the nearer of the two response locations, regardless of the location of the stimulus. This was interpreted as a specific impairment in generating responses in contralateral space. In contrast, no comparable deficit was seen when the animals performed the task on the side ipsilateral to the lesion. Additional postoperative challenges, in which response options were presented bilaterally, showed this response deficit to be defined in egocentric coordinates, with the severest response deficits for the most contralateral locations.
Experience-Dependent Modifications in MAP2 Phosphorylation in Rat Olfactory Bulb
Authors: Philpot Benjamin D. , Lim Jae H. , Halpain Shelley , Brunjes Peter C. 
Published: April 2018

Microtubule-associated protein 2 (MAP2) is a neuron-specific cytoskeletal protein, enriched in dendrites and cell bodies, that helps determine dendritic shape. MAP2 regulates microtubule stability in a phosphorylation-dependent manner. The present study used immunocytochemistry with phosphoepitope-specific and phosphorylation state-independent antibodies to examine experience-dependent changes in MAP2 expression during postnatal development of the olfactory bulb. Our results demonstrate that immunoreactivity reflecting total MAP2 expression reaches a maximal level by postnatal day 20 (P20). The degree of staining for phosphoindependent forms of MAP2 is relatively unaffected by blocking odorant passage to one half the nasal epithelium via unilateral naris closure, a manipulation that attenuates physiological activity in the bulb. However, olfactory restriction from P1 dramatically reduces immunoreactivity for antibody AP18, which recognizes MAP2 only when phosphorylated on Ser136. Quantification of staining in the granule cell layer indicates that the greatest difference (64%) between control and experimental bulbs occurs after occlusion from P1 to P30 compared with animals deprived from P1 to P10 or P1 to P20. The shift in MAP2 phosphorylation occurs even when deprivation is delayed until P30, after the sensitive period for experience-dependent changes in bulb volume. Thus, the degree of the phosphorylation shift depends on the duration but not the time of onset of naris closure.Because staining for phosphorylation-independent forms of MAP2 is unchanged by naris closure, the total amount of the protein per unit area is probably not significantly altered. However, the large reductions of AP18-immunoreactivity in the bulb after olfactory restriction suggest that there is an activity-dependent stimulation of MAP2 phosphorylation.
Cross-Modal Transfer of Information between the Tactile and the Visual Representations in the Human Brain: A Positron Emission Tomographic Study
Authors: Hadjikhani Nouchine , Roland Per E. 
Published: April 2018

Positron emission tomography in three-dimensional acquisition mode was used to identify the neural populations involved in tactile–visual cross-modal transfer of shape. Eight young male volunteers went through three runs of three different matching conditions: tactile–tactile (TT), tactile–visual (TV), and visual–visual (VV), and a motor control condition. Fifteen spherical ellipsoids were used as stimuli.By subtracting the different matching conditions and calculating the intersections of statistically significant activations, we could identify cortical functional fields involved in the formation of visual and tactile representation of the objects alone and those involved in cross-modal transfer of the shapes of the objects.Fields engaged in representation of visual shape, revealed in VV–control, TV–control and TV–TT, were found bilaterally in the lingual, fusiform, and middle occipital gyri and the cuneus. Fields engaged in the formation of the tactile representation of shape, appearing in TT–control, TV–control and TV–VV, were found in the left postcentral gyrus, left superior parietal lobule, and right cerebellum.Finally, fields active in both TV–VV and TV–TT were considered as those involved in cross-modal transfer of information. One field was found, situated in the right insula–claustrum. This region has been shown to be activated in other studies involving cross-modal transfer of information. The claustrum may play an important role in cross-modal matching, because it receives and gives rise to multimodal cortical projections. We propose here that modality-specific areas can communicate, exchange information, and interact via the claustrum.
Synaptic Structure and Transmitter Release in Crustacean Phasic and Tonic Motor Neurons
Authors: Msghina M. , Govind C. K. , Atwood H. L. 
Published: April 2018

The paired phasic and tonic motor neurons supplying the extensor muscle in the crayfish leg were investigated to establish whether differences in synaptic structure could account for large differences in transmitter release at the neuromuscular junctions. Nerve terminals with transmitter release that had been assessed from recordings made with a focal “macro-patch” electrode were subsequently labeled, processed for electron microscopy, and reconstructed from serial sections.At a frequency of 1 Hz, quantal contents of phasic terminals were 90–1300 times greater than those of tonic terminals when both were recorded at the same location. At higher frequencies, facilitation was pronounced at tonic, but not phasic, terminals.Reconstructions of recording sites showed that both phasic and tonic terminals possessed many small synapses, usually with one or more structurally defined active zones. Mean synaptic contact area was larger for tonic terminals, and the number of individual synapses per length of nerve terminal was also larger. Active zones were not different in size for the two terminals.At low frequencies, quantal emission per synapse is much greater for phasic terminals. The higher quantal content of phasic terminals and their synapses cannot reasonably be accounted for by more or larger synapses or active zones at the recording sites. Because structural features alone are not likely to produce the very large differences in quantal content of phasic and tonic terminals observed at low stimulation frequencies, it is likely that other properties of the nerve terminal are largely responsible for these differences.
Cytoskeletal Actin Gates a Cl−Channel in Neocortical Astrocytes
Authors: Lascola Christopher D. , Nelson Deborah J. , Kraig Richard P. 
Published: April 2018

Increases in astroglial Cl−conductance accompany changes in cell morphology and disassembly of cytoskeletal actin, but Cl−channels underlying these conductance increases have not been described. We characterize an outwardly rectifying Cl−channel in rodent neocortical cultured astrocytes and describe how cell shape and cytoskeletal actin modulate channel gating. In inside-out patch-clamp recordings from cultured astrocytes, outwardly rectifying Cl−channels either were spontaneously active or inducible in quiescent patches by depolarizing voltage steps. Average single-channel conductance was 36 pS between −60 and −80 mV and was 75 pS between 60 and 80 mV in symmetrical (150 mmNaCl) solutions. The permeability ratio (PNa/PCl) was 0.14 at lower ionic strength but increased at higher salt concentrations. Both ATP and 4,4-diisothiocyanostilbene-2,2′-disulfonic acid produced a flicker block, whereas Zn2+produced complete inhibition of channel activity.The frequency of observing both spontaneous and inducible Cl−channel activity was markedly higher in stellate than in flat, polygonally shaped astrocytes. In addition, cytoskeletal actin modulated channel open-state probability (PO) and conductance at negative membrane potentials, controlling the degree of outward rectification. Direct application of phalloidin, which stabilizes actin, preserved lowPOand promoted lower conductance levels at negative potentials. LowerPOalso was induced by direct application of polymerized actin. The actions of phalloidin and actin were reversed by coapplication of gelsolin and cytochalasin D, respectively. These results provide the first report of an outwardly rectifying Cl−channel in neocortical astrocytes and demonstrate how changes in cell shape and cytoskeletal actin may control Cl−conductance in these cells.