bluuebunny/crossref_metadata_2025_split huggingface dataset:
High-Frequency Oscillations in the Output Networks of the Hippocampal–Entorhinal Axis of the Freely Behaving Rat
Authors: Chrobak James J. , Buzsáki Gyorgy 
Published: April 2018

Population bursts of the CA3 network, which occur during eating, drinking, awake immobility, and slow-wave sleep, produce a large field excitatory postsynaptic potential throughout stratum radiatum of the CA1 field (sharp wave). The CA3 burst sets into motion a short-lived, dynamic interaction between CA1 pyramidal cells and interneurons, the product of which is a 200 Hz oscillatory field potential (ripple) and phase-related discharge of the CA1 network. Although many CA1 pyramidal neurons discharge during the time frame (50–100 msec) of each sharp wave, each wave of a ripple (∼5 msec) reflects the synchronization of more discrete subsets of CA1 neurons.When we used multi-site recordings in freely behaving rats, we observed ripples throughout the longitudinal extent (∼4–5 mm) of the dorsal CA1 region that were coherent for multiple cycles of each ripple. High-frequency ripples were also observed throughout the hippocampal–entorhinal output pathway that were concurrent but less coherent on a cycle-by-cycle basis. Single and multiunit neuronal activity was phase-related to local ripples throughout the hippocampal–entorhinal output pathway. Entorhinal ripples occurred 5–30 msec after the CA1 ripples and were related to the occurrence of an entorhinal sharp wave. Thus, during each hippocampal sharp wave, there is a powerful synchronization among the neuronal networks that connect the hippocampus to the neocortex. We suggest that this population interaction (1) biologically constrains theoretical models of hippocampal function and dysfunction and (2) has the capacity to support an “off-line” memory consolidation process.
Increased Expression of IL-1β Converting Enzyme in Hippocampus after Ischemia: Selective Localization in Microglia
Authors: Bhat Ratan V. , DiRocco Richard , Marcy Val R. , Flood Dorothy G. , Zhu Yuan , Dobrzanski Pawel , Siman Robert , Scott Richard , Contreras Patricia C. , Miller Matthew 
Published: April 2018

Although the interleukin-1β converting enzyme (ICE)/CED-3 family of proteases has been implicated recently in neuronal cell deathin vitroandin ovo, the role of specific genes belonging to this family in cell death in the nervous system remains unknown. To address this question, we examined thein vivoexpression of one of these genes,Ice, after global forebrain ischemia in gerbils. Using RT-PCR and Western immunoblot techniques, we detected an increase in the mRNA and protein expression of ICE in hippocampus during a period of 4 d after ischemia. Chromatin condensation was observed in CA1 neurons within 2 d after ischemia. Internucleosomal DNA fragmentation and apoptotic bodies were observed between 3 and 4 d after ischemia, a period during which CA1 neuronal death is maximal. In nonischemic brains, ICE-like immunoreactivity was relatively low in CA1 pyramidal neurons but high in scattered hippocampal interneurons. After ischemia, ICE-like immunoreactivity was not altered in these neurons. ICE-like immunoreactivity, however, was observed in microglial cells in the regions adjacent to the CA1 layer as early as 2 d after ischemic insult. The increase in ICE-like immunoreactivity was robust at 4 d after ischemia, a period that correlates with the DNA fragmentation observed in hippocampal homogenates of ischemic brains. These results provide the first evidence for the localization and induction of ICE expressionin vivoafter ischemia and suggest an indirect role for ICE in ischemic damage through mediation of an inflammatory response.
Ultrastructural Immunocytochemical Localization of μ-Opioid Receptors in Rat Nucleus Accumbens: Extrasynaptic Plasmalemmal Distribution and Association with Leu5-Enkephalin
Authors: Svingos Adena L. , Moriwaki Akiyoshi , Wang Jia Bei , Uhl George R. , Pickel Virginia M. 
Published: April 2018

μ-Opioid receptors and their endogenous ligands, including Leu5-enkephalin (LE), are distributed abundantly in the nucleus accumbens (NAC), a region implicated in mechanisms of opiate reinforcement. We used immunoperoxidase and/or immunogold–silver methods to define ultrastructural sites for functions ascribed to μ-opioid receptors and potential sites for activation by LE in the NAC. An antipeptide antibody raised against an 18 amino acid sequence of the cloned μ-opioid receptor (MOR) C terminus showed that MOR-like immunoreactivity (MOR-LI) was localized predominantly to extrasynaptic sites along neuronal plasma membranes. The majority of neuronal profiles containing MOR-LI were dendrites and dendritic spines. The dendritic plasma membranes immunolabeled for MOR were near sites of synaptic input from LE-labeled terminals and other unlabeled terminals forming either inhibitory or excitatory type synapses. Unmyelinated axons and axon terminals were also intensely but less frequently immunoreactive for MOR. Observed sites for potential axonal associations with LE included coexistence of MOR and LE within the same terminal, as well as close appositions between differentially labeled axons. Astrocytic processes rarely contained detectable MOR-LI, but also were sometimes observed in apposition to LE-labeled terminals. We conclude that in the rat NAC, MOR is localized prominently to extrasynaptic neuronal and more rarely to glial plasma membranes that are readily accessible to released LE and possibly other opioid peptides and opiate drugs. The close affiliation of MOR with spines receiving excitatory synapses and dendrites receiving inhibitory synapses provides the first direct morphological evidence that MOR selectively modulates postsynaptic responses to cortical and other afferents.
Visual Motion-Detection Circuits in Flies: Small-Field Retinotopic Elements Responding to Motion Are Evolutionarily Conserved across Taxa
Authors: Buschbeck Elke K. , Strausfeld Nicholas J. 
Published: April 2018

The Hassenstein–Reichardt autocorrelation model for motion computation was derived originally from studies of optomotor turning reactions of beetles and further refined from studies of houseflies. Its application for explaining a variety of optokinetic behaviors in other insects assumes that neural correlates to the model are principally similar across taxa. This account examines whether this assumption is warranted. The results demonstrate that an evolutionarily conserved subset of neurons corresponds to small retinotopic neurons implicated in motion-detecting circuits that link the retina to motion-sensitive neuropils of the lobula plate. The occurrence of these neurons in basal groups suggests that they must have evolved at least 240 million years before the present time. Functional contiguity among the neurons is suggested by their having layer relationships that are independent of taxon-specific variations such as medulla stratification, the shape of terminals or dendrites, the presence of other taxon-specific neurons, or the absence of orientation-specific motion-sensitive levels in the lobula plate.
Major Histocompatibility Class II Molecules in the CNS: Increased Microglial Expression at the Onset of Narcolepsy in a Canine Model
Authors: Tafti Mehdi , Nishino Seiji , Aldrich Michael S. , Liao Wennie , Dement William C. , Mignot Emmanuel 
Published: April 2018

Human narcolepsy is a neurological disorder known to be closely associated with HLA-DR2 and DQB1*0602. Because most autoimmune diseases are HLA-associated, a similar mechanism has been proposed for narcolepsy. However, neither systemic nor CNS evidence of an autoimmune abnormality has ever been reported. In this study, major histocompatibility (MHC) class I and class II expression was studied in the CNS of human and canine narcoleptics using immunohistochemistry and Northern analysis. Results indicate that canine narcolepsy is associated with a significant increase of MHC class II expression by the microglia. Moreover, the highest values were found between 3 and 8 months of age, strikingly concomitant to the development of narcolepsy in the canine model. In humans, class II expression was not found significantly different between control and narcoleptic subjects. This result could be explained by the old age of the subjects (69.86 ± 5.31 and 68.36 ± 4.74 years in narcoleptics and controls, respectively), because class II expression is significantly correlated with age in both humans and dogs. For the first time, this study demonstrated that the expression of MHC class II molecules in the CNS is age-dependent and that a consistent increase of their expression by the microglia might be critically involved in the development of narcolepsy.
Protection of the Neostriatum against Excitotoxic Damage by Neurotrophin-Producing, Genetically Modified Neural Stem Cells
Authors: Martı́nez-Serrano Alberto , Björklund Anders 
Published: April 2018

Huntington’s disease is a progressive neurodegenerative disease that affects the striatum, above all, the GABAergic striatal projection neurons. In the present study, we have explored the use of genetically modified neural stem cell lines producing nerve growth factor (NGF) or brain-derived neurotrophic factor (BDNF) as a means to protect the striatal neurons against excitotoxic damage after transplantation to the striatum, 1 week before the injection of quinolinic acid into the same area. One month after the lesion, striatal degeneration, lesion size, and loss of DARPP-32-positive projection neurons were only slightly affected by the BDNF-secreting cells, but substantially prevented when NGF-producing stem cells were used as a source of exogenous trophic factor; innervation of the target fields (pars reticulata of the substantia nigra and the globus pallidus) was preserved as well. Cholinergic striatal interneurons (choline acetyltransferase-immunoreactive) were affected by the lesion and completely rescued by the NGF-transduced cells. The astroglial and microglial reactions to the excitotoxic lesion were substantially reduced in the striata, which had received transplants of NGF-producing cells. The generalized protective effects of the NGF-producing cell grafts in this model are discussed in the context of an indirect action preventing the development of toxicity mediated by cellular elements in the host striatum in response to the excitotoxin. We conclude that continuous supply of trophic factors by means of genetically modified neural stem cells represents a highly effective procedure to counteract neuronal degeneration in the excitotoxically lesioned striatum.
Functional NMDA Receptors Are Transiently Active and Support the Survival of Purkinje Cells in Culture
Authors: Yuzaki Michisuke , Forrest Douglas , Verselis Lynne M. , Sun Shaiu C. , Curran Tom , Connor John A. 
Published: April 2018

Conflicting evidence exists concerning the activity of NMDA receptors (NMDARs) in cerebellar Purkinje cells and their possible functions. To investigate the activity of NMDARs, we used whole-cell recording on immunocytochemically identified Purkinje cells in primary culture. In addition, we used mice with a disrupted NMDAR1 gene that lack functional NMDARs (NR1−/−) to assess the physiological role of NMDARs. In cultures from normal mice, NMDA-mediated currents were detected in all identified Purkinje cells at 4 din vitro(div). After 14 d, however, NMDA responses were reduced in amplitude, whereas the responses to kainate and glutamate increased steadily in amplitude. In addition, the NMDA-induced current displayed a pronounced desensitization at these later stages; peak current declined to zero during steady application of NMDA. At 7 div, the number of surviving Purkinje cells was less in cultures treated with NMDA antagonists, and their survival was dose-dependent. Purkinje cell survival was correspondingly poorer in cultures from the NR1−/− mice than in wild-type controls, suggesting that NMDAR activity enhances the survival of Purkinje cellsin vitro. The addition of moderate doses of NMDA promoted the survival of wild-type Purkinje cells in the presence of tetrodotoxin. Feeder layers of cerebellar granule cells derived from wild-type or NR1−/− mice promoted survival of Purkinje cells to a similar degree, suggesting that the NMDAR in Purkinje cells, but not in other cells, is directly involved in Purkinje cell viability. The results demonstrate that NMDARs transiently produce membrane current in Purkinje cells and may serve as one of the epigenetic factors that support the survival of Purkinje cellsin vitro.
Synchronous Onset of NGF and TrkA Survival Dependence in Developing Dorsal Root Ganglia
Authors: White Fletcher A. , Silos-Santiago Inmaculada , Molliver Derek C. , Nishimura Merry , Phillips Heidi , Barbacid Mariano , Snider William D. 
Published: April 2018

Determinations of dorsal root ganglion (DRG) neuron loss in nerve growth factor (NGF) and neurotrophin-3 (NT-3) null mutant mice have supported the concept that neurons can switch neurotrophin dependence by revealing that many neurons must require both of these factors acting either sequentially or simultaneously during development. The situation is complex, however, in thatNT-3(−/−)mutant mice show far greater neuron loss than mice deficient in the NT-3 receptor TrkC, suggesting that NT-3 may support many DRG neurons via actions on the NGF receptor TrkA. To assess the possibility of ligand-receptor cross-talk as a developmental mechanism, we have compared the onset of survival dependence of lumbar DRG neurons on NT-3, TrkC, NGF, and TrkA signaling in mice deficient in these molecules as a result of gene targeting. At embryonic day 11.5 (E11.5), virtually all lumbar DRG cells express TrkC mRNA and many require NT-3 and TrkC signaling for survival. In contrast, although many lumbar DRG cells also express TrkA at E11.5, there is little survival dependence on TrkA signaling. By E13.5, most lumbar DRG cells have downregulated TrkC mRNA. The onset of survival dependence on NGF and TrkA-signaling is concurrent and of equal magnitude at E13.5, demonstrating that NT-3 alone does not support DRG neurons via TrkA, nor can NT-3 compensate for the loss of NGF. We conclude that many murine DRG cells require NT-3 for survival before exhibiting NGF dependence and that NT-3 activation of TrkA is unimportant to these early NT-3 survival-promoting actions. We suggest that the discrepancy in cell loss betweenNT-3(−/−)andtrkC(−/−)mutants is attributable to the ability of NT-3 to support DRG neurons via TrkA in the artificial situation where TrkC is absent.
Functional GABAergic Synaptic Connection in Neonatal Mouse Barrel Cortex
Authors: Agmon Ariel , Hollrigel Greg , O’Dowd Diane K. 
Published: April 2018

Intracortical inhibition is crucial to proper functioning of the mature neocortex, yet, paradoxically, is reported to be rare or absent in the neonatal animal. We reexamined this issue by recording whole-cell postsynaptic currents (PSCs) of barrel cortex neurons in thalamocortical brain slices from neonatal mice. Monosynaptic, excitatory thalamocortical responses were elicited in layers V/VI neurons as early as postnatal day 0 (P0, the first 24 hr after birth) and in presumptive layer IV as early as P2. At very low stimulation frequencies, the monosynaptic response was invariably followed by a prolonged (up to 1 sec) synaptic barrage, which fatigued at stimulus repetition rates of 2/min or higher. This barrage consisted of postsynaptic responses to spiking activity in neighboring cortical cells, because (1) it could also be evoked by intracortical stimulation in coronal slices and (2) it was abolished by antagonists to NMDA receptors (NMDARs), even when NMDARs on the recorded cell were under a voltage-dependent block. Some of the larger polysynaptic events changed polarity at a negative reversal potential and were blocked by GABAAreceptor (GABAAR) antagonists, with a concurrent enhancement of the extracellular field potential, indicating that they were GABAAR- mediated, Cl-dependent inhibitory PSCs (IPSCs). We conclude that a network of functional intracortical GABAAR-mediated synaptic connections exists from the earliest postnatal ages, although it gives rise to responses that differ from mature IPSCs in reversal potential and latency.
Compartmental Localization of a Metabotropic Glutamate Receptor (mGluR7): Two Different Active Sites at a Retinal Synapse
Authors: Brandstätter Johann Helmut , Koulen Peter , Kuhn Rainer , van der Putten Herman , Wässle Heinz 
Published: April 2018

The distribution of the metabotropic glutamate receptor 7 (mGluR7) was studied in the rat retina using a specific antiserum. Punctate immunofluorescence that corresponded to synaptic localization was present exclusively in the inner plexiform layer. Double-labeling experiments suggested that mGluR7 is expressed at the synaptic terminals of certain cone bipolar cells. Electron microscopy showed that mGluR7 was present both presynaptically, as an autoreceptor in cone bipolar cell ribbon synapses, and postsynaptically in amacrine cells. There are usually two postsynaptic processes at a bipolar cell ribbon synapse; however, the presynaptic aggregation of mGluR7 was restricted to one half of the active zone and therefore was opposed to only one of the postsynaptic processes. This selective localization of mGluR7 could differentially regulate the glutamate release from the ribbon synapse, thus leading to a differential activation of the postsynaptic neurons.
Use-Dependent Exaggeration of Neuronal Injury after Unilateral Sensorimotor Cortex Lesions
Authors: Kozlowski Dorothy A. , James Debra C. , Schallert Timothy 
Published: April 2018

Unilateral injury to the forelimb representation area of the sensorimotor cortex (FL-SMC) in adult rats causes over-reliance on the unimpaired forelimb for postural-motor movements, as well as overgrowth of layer V pyramidal cell dendrites in the homotopic cortex of the noninjured hemisphere. The overgrowth appears to be use-dependent because it can be prevented by restricting movements of the unimpaired forelimb. Additionally, restricting the unimpaired forelimb in animals with FL-SMC damage results in significantly greater behavioral dysfunction when examined 2 d after cast removal (compared to that after impaired-limb immobilization, or no limb immobilization). In the present study, the long-term behavioral and anatomical effects of limb immobilization were examined. Animals with FL-SMC lesions were fitted with casts immediately after the lesion that immobilized the impaired forelimb, the unimpaired forelimb, or neither forelimb for 15 d. Immobilization of the nonimpaired forelimb resulted in chronic prevention of dendritic growth and severe and chronic behavioral deficits. In addition, immobilization of the nonimpaired forelimb resulted in a dramatic exaggeration of the neuronal injury, presumably attributable to forced overuse of the impaired limb. Immobilization of the impaired forelimb resulted in no detectable neural changes and in only slightly increased and longer-lasting behavioral asymmetries (compared to nonimmobilized, lesioned animals), presumably attributable to mild disuse of the impaired limb. Immobilization of a single forelimb in nonlesioned rats resulted in no significant behavioral or anatomical changes. Together, these results suggest that although behavioral experience can enhance neural growth after brain injury, the region surrounding the injury may be vulnerable to behavioral pressure during the early postlesion period.
Dextroamphetamine Enhances “Neural Network-Specific” Physiological Signals: A Positron-Emission Tomography rCBF Study
Authors: Mattay Venkata S. , Berman Karen Faith , Ostrem Jill L. , Esposito Giuseppe , Van Horn John D. , Bigelow Llewellyn B. , Weinberger Daniel R. 
Published: April 2018

Previous studies in animals and humans suggest that monoamines enhance behavior-evoked neural activity relative to nonspecific background activity (i.e., increase signal-to-noise ratio). We studied the effects of dextroamphetamine, an indirect monoaminergic agonist, on cognitively evoked neural activity in eight healthy subjects using positron-emission tomography and the O15water intravenous bolus method to measure regional cerebral blood flow (rCBF). Dextroamphetamine (0.25 mg/kg) or placebo was administered in a double-blind, counterbalanced design 2 hr before the rCBF study in sessions separated by 1–2 weeks. rCBF was measured while subjects performed four different tasks: two abstract reasoning tasks—the Wisconsin Card Sorting Task (WCST), a neuropsychological test linked to a cortical network involving dorsolateral prefrontal cortex and other association cortices, and Ravens Progressive Matrices (RPM), a nonverbal intelligence test linked to posterior cortical systems—and two corresponding sensorimotor control tasks. There were no significant drug or task effects on pCO2or on global blood flow. However, the effect of dextroamphetamine (i.e., dextroamphetamine vs placebo) on task-dependent rCBF activation (i.e., task − control task) showed double dissociations with respect to task and region in the very brain areas that most distinctly differentiate the tasks. In the superior portion of the left inferior frontal gyrus, dextroamphetamine increased rCBF during WCST but decreased it during RPM (ANOVAF(1,7) = 16.72, p < 0.0046). In right hippocampus, blood flow decreased during WCST but increased during RPM (ANOVAF(1,7) = 18.7, p < 0.0035). These findings illustrate that dextroamphetamine tends to “focus” neural activity, to highlight the neural network that is specific for a particular cognitive task. This capacity of dextroamphetamine to induce cognitively specific signal augmentation may provide a neurobiological explanation for improved cognitive efficiency with dextroamphetamine.
Impaired Cerebellar Synaptic Plasticity and Motor Performance in Mice Lacking the mGluR4 Subtype of Metabotropic Glutamate Receptor
Authors: Pekhletski Roman , Gerlai Robert , Overstreet Linda S. , Huang Xi-Ping , Agopyan Nadia , Slater N. Traverse , Abramow-Newerly Wanda , Roder John C. , Hampson David R. 
Published: April 2018

The application of the glutamate analogl-2-amino-4-phosphonobutyric acid (l-AP4) to neurons produces a suppression of synaptic transmission. Althoughl-AP4 is a selective ligand at a subset of metabotropic glutamate receptors (mGluRs), the precise physiological role of thel-AP4-activated mGluRs remains primarily unknown. To provide a better understanding of the function ofl-AP4 receptors, we have generated and studied knockout (KO) mice lacking the mGluR4 subtype of mGluR that displays high affinity forl-AP4. The mGluR4 mutant mice displayed normal spontaneous motor activity and were unimpaired on the bar cross test, indicating that disruption of the mGluR4 gene did not cause gross motor abnormalities, impairments of novelty-induced exploratory behaviors, or alterations in fine motor coordination. However, the mutant mice were deficient on the rotating rod motor-learning test, suggesting that mGluR4 KO mice may have an impaired ability to learn complex motor tasks. Patch-clamp and extracellular field recordings from Purkinje cells in cerebellar slices demonstrated thatl-AP4 had no effect on synaptic responses in the mutant mice, whereas in the wild-type mice 100 μml-AP4 produced a 23% depression of synaptic responses with an EC50of 2.5 μm. An analysis of presynaptic short-term synaptic plasticity at the parallel fiber→Purkinje cell synapse demonstrated that paired-pulse facilitation and post-tetanic potentiation were impaired in the mutant mice. In contrast, long-term depression (LTD) was not impaired. These results indicate that an important function of mGluR4 is to provide a presynaptic mechanism for maintaining synaptic efficacy during repetitive activation. The data also suggest that the presence of mGluR4 at the parallel fiber→Purkinje cell synapse is required for maintaining normal motor function.