bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cellular Mechanisms of the Augmenting Response: Short-Term Plasticity in a Thalamocortical Pathway
Authors: Castro-Alamancos Manuel A. , Connors Barry W. 
Published: April 2018

Some thalamocortical pathways display an “augmenting response” when stimuli are delivered at frequencies between 7 and 14 Hz. Cortical responses to the first three stimuli of a series increase progressively in amplitude and are relatively stable thereafter. We have investigated the cellular mechanisms of the augmenting response using extracellular and intracellular recordingsin vivoand in slices of the sensorimotor neocortex of the rat.Single stimuli to the ventrolateral (VL) nucleus of the thalamus generate EPSPs followed by feedforward IPSPs that hyperpolarize cells in layer V. A long-latency depolarization interrupts the IPSP with a peak at ∼200 msec. A second VL stimulus delivered during the hyperpolarization and before the peak of the long-latency depolarization yields an augmenting response. The shortest latency for augmenting responses occurs in cells of layer V, and they appear in dendrites and somata recorded in upper layers ∼5 msec later. Recordingsin vitroshow that some layer V cells have hyperpolarization-activated and deinactivated conductances that may serve to increase their excitability after IPSPs. Alsoin vitro, cells from layer V, but not from layer III, generated augmenting responses at the same stimulation frequencies that were effectivein vivo. Control experiments indicated that neither paired-pulse depression of IPSPs nor presynaptically mediated facilitation can account for the augmenting response. Active dendritic conductances contribute to the spread of augmenting responses into upper layers by way of back-propagating fast spikes, which attenuate with repetition, and long-lasting spikes, which enhance in parallel with the augmenting response. In conclusion, we propose that the initiation of augmenting responses depends on an interaction between inhibition, intrinsic membrane properties, and synaptic interconnections of layer V pyramidal neurons.
Passive and Active Membrane Properties Contribute to the Temporal Filtering Properties of Midbrain NeuronsIn Vivo
Authors: Fortune Eric S. , Rose Gary J. 
Published: April 2018

This study examined the contributions of passive and active membrane properties to the temporal selectivities of electrosensory neuronsin vivo. The intracellular responses to time-varying (2–30 Hz) electrosensory stimulation and current injection of 27 neurons in the midbrain of the weakly electric fishEigenmanniawere recorded. Each neuron was filled with biocytin to reveal its anatomy.Neurons were divided into two biophysically distinct groups based on their frequency-dependent responses to sinusoidal current injection over the range 2–30 Hz. Fourteen neurons showed low-pass filtering, with a maximum decline in the amplitude of voltage responses of >2.6 dB (X= 4.30 dB,s= 1.10 dB) to sinusoidal current injection. These neurons also showed low-pass filtering of electrosensory information but with larger maximum declines in postsynaptic potential amplitude (X= 9.53 dB,s= 3.34 dB;n= 10). These neurons had broad dendritic arbors and relatively spiny dendrites. Five neurons showed all-pass filtering, having maximum decline in the amplitude of voltage responses of <2.0 dB (X= 1.16 dB,s= 0.61 dB). For electrosensory stimuli, however, these neurons showed low-, band-, or high-pass filtering. These neurons had small dendritic arbors and few or no spines.Voltage-dependent “active” conductances were revealed in eight neurons by using several levels of current clamp. In four of these neurons, the duration of the voltage-dependent conductances decreased in concert with the period of the electrosensory stimulus, whereas in the other four neurons the duration of the voltage-dependent conductances was relatively short (<30 msec) and nearly constant across sensory stimulation frequencies. These conductances enhanced the temporal filtering properties of neurons.
Preferential Termination of Corticorubral Axons on Spine-Like Dendritic Protrusions in Developing Cat
Authors: Saito Yasuhiko , Song Wen-Jie , Murakami Fujio 
Published: April 2018

The formation of synaptic contacts is a crucial event during neural development and is thought to be achieved by complex interactions between incoming axons and the neurons in the target. We have focused on spine-like dendritic protrusions (SLDPs), which are transient pleomorphic protrusive structures seen in developing brains. Although the functional significance of SLDPs remains unknown, accumulatingin vitroevidence suggests that the SLDP plays an important role in synaptogenetic interactions with axons. As a test of this idea, the present study was performed to examine whether the SLDPs are the preferential sites of synapse formationin vivo.The ultrastructure of biocytin-labeled corticorubral (CR) terminals was examined in serial thin sections during the period of synaptogenesis in newborn cats. We found that a major proportion (86%) of the CR synapses was formed on SLDPs. The presynaptic terminals were often invaginated by fine processes extending from the tips of SLDPs. Synaptic structures presumably of cortical origin were also found on SLDPs of HRP-labeled rubrospinal cells, suggesting that SLDPs postsynaptic to labeled CR terminals originate at least in part from rubrospinal cells. Taken together, these results indicate that SLDPs may represent preferred sites of synapse formation and support the notion that SLDPs play a role in synaptogenic interactions during brain development.
An Initial, Three-Day-Long Treatment with Alcohol Induces a Long-Lasting Phenomenon of Selective Tolerance in the Activity of the Rat Hypothalamic–Pituitary–Adrenal Axis
Authors: Lee Soon , Rivier Catherine 
Published: April 2018

We determined whether an initial alcohol challenge induced long-lasting changes in the activity of the hypothalamic–pituitary–adrenal (HPA) axis. Adult male rats received intragastric injections of the vehicle or a moderately intoxicating dose of alcohol (3.0 gm/kg) daily for 3 d. When animals were acutely challenged with alcohol 3–12 d later, their ACTH and corticosterone responses were significantly blunted, compared with that of vehicle-pretreated rats. In contrast, exposure to mild electric foot shocks induced a pattern of ACTH secretion that was comparable in animals administered alcohol or the vehicle previously, indicating a lack of cross-tolerance. No significant differences were observed in pituitary responsiveness to corticotropin-releasing factor or vasopressin in rats pretreated with the vehicle or alcohol. The influence of the initial drug treatment was not mimicked by exposure to foot shocks, nor was it prevented by administering a potent corticotropin-releasing factor antagonist to block the elevations in plasma ACTH and corticosterone induced by this initial treatment. Finally, we found that rats injected initially with the vehicle and challenged subsequently with alcohol exhibited the expected increased neuronal activation (measured by the upregulation of steady-state mRNA and protein levels of immediate early genes) in the paraventricular nucleus of their hypothalamus. In contrast, this response was markedly decreased in animals exposed previously to the drug.To our knowledge, this is the first report that exposure to a stress (i.e., alcohol), although not immediately altering the response of the HPA axis to this particular signal, induces a selective tolerance that is both slow to develop and long-lasting. The primary mechanism mediating the ability of an initial drug treatment to decrease subsequent responses of the HPA axis to a second drug challenge seems to be the inability of hypothalamic neurons to respond adequately to this second challenge.
Crossed Rhythmic Synaptic Input to Motoneurons during Selective Activation of the Contralateral Spinal Locomotor Network
Authors: Kjaerulff Ole , Kiehn Ole 
Published: April 2018

To investigate the cellular mechanisms underlying locomotor-related left–right coordination, we monitored the crossed synaptic input to lumbar motoneurons during contralateral ventral root rhythmicity in the neonatal rat spinal cordin vitro. Using a longitudinal split-bath setup, one hemicord was kept in normal solution, whereas the contralateral hemicord was exposed to 5-HT and NMDA. With this approach, rhythmic bursting could be induced in the ventral roots on the agonist-exposed side, whereas the ventral roots on the agonist-free side remained silent. Intracellular recordings were made from L1–L3 motoneurons on the silent agonist-free side during rhythmic activity in the contralateral ventral roots. At the resting membrane potential, the typical crossed synaptic input was a rhythmic barrage of depolarizing IPSPs. This input modulated the frequency of spikes induced with depolarizing direct current by inhibiting firing in phase with the contralateral bursts. Intracellular chloride loading increased the amplitude of the IPSPs, suggesting that they were chloride-dependent. Strychnine but not bicuculline generally blocked the rhythmic inhibitory input when added to the agonist-free side during contralateral rhythmicity. APV and CNQX on the agonist-free side abolished the rhythmic inhibitory input in most motoneurons but not in all.We suggest that rat spinal motoneurons receive a mainly glycinergic rhythmic inhibition from the contralateral half of the locomotor network. Unlike in simpler vertebrates, the crossed inhibition often appears to be at least disynaptic, involving inhibitory premotor neurons located on the same side as the receiving motoneurons. These premotor neurons are rhythmically excited via a crossed pathway that depends on glutamatergic transmission.
Activation of Coeruleospinal Noradrenergic Inhibitory Controls during Withdrawal from Morphine in the Rat
Authors: Rohde Dana S. , Basbaum Allan I. 
Published: April 2018

We previously reported that withdrawal from morphine induces the expression of Fos, a marker of neuronal activity, in spinal cord neurons, particularly in laminae I and II of the superficial dorsal horn, and that the magnitude of Fos expression is increased in rats with a midthoracic spinal transection. We suggested that loss of withdrawal-associated increases in descending inhibitory controls that arise in the brainstem underlie the increased Fos expression after spinal transection. Here, we addressed the origin of the supraspinal inhibition. We injected rats intracerebroventricularly with saline or anti-dopamine-β-hydroxylase–saporin, a toxin that destroys noradrenergic neurons of the locus coeruleus. Eleven days later, we implanted rats with morphine or placebo pellets, and after 4 d, we precipitated withdrawal with naltrexone. One hour later, the rats were killed, their brains and spinal cords were removed, and transverse sections of the brains and spinal cords were immunoreacted with an antibody to Fos.In placebo-pelleted rats, the toxin injection did not alter behavior and did not induce expression of the Fos protein. However, compared with saline-injected withdrawing rats, the toxin-treated rats that underwent withdrawal demonstrated an intense withdrawal behavior rarely seen in the absence of toxin, namely forepaw fluttering. The rats also had significantly increased Fos-like immunoreactivity in all laminae of the cervical cord and in laminae I and II and the ventral horn of the lumbar cord. No differences were recorded in the sacral cord. We conclude that the effects of spinal transection in rats that withdraw from morphine in part reflect a loss of coeruleospinal noradrenergic inhibitory controls.
Cyclosporin A, But Not FK 506, Protects Mitochondria and Neurons against Hypoglycemic Damage and Implicates the Mitochondrial Permeability Transition in Cell Death
Authors: Friberg Hans , Ferrand-Drake Michel , Bengtsson Finn , Halestrap Andrew P. , Wieloch Tadeusz 
Published: April 2018

Induction of the mitochondrial permeability transition (MPT) has been implicated in cellular apoptosis and in ischemia–reperfusion injury. During MPT, a channel in the inner mitochondrial membrane, the mitochondrial megachannel, opens and causes isolated mitochondria to swell. MPT and mitochondrial swelling is inhibited by cyclosporin A (CsA), which may also inhibit apoptosis in some cells.Treatment with CsA (50 mg/kg, i.v.) showed a robust reduction of brain damage when administered 30 min before insulin-induced hypoglycemic isoelectricity of 30 min duration. Ultrastructural examination of the dentate gyrus revealed a marked swelling of dendrites and mitochondria during the hypoglycemic insult. In CsA-treated animals, mitochondria resumed a normal and contracted appearance during and after the hypoglycemic insult. Treatment with FK 506 (2 mg/kg, i.v.), a compound with immunosuppressive action similar to that of CsA, was not protective. Studies on the swelling kinetics of isolated mitochondria from the hippocampus showed that CsA, but not FK 506, inhibits calcium ion-induced MPT.We conclude that CsA treatment during hypoglycemic coma inhibits the MPT and reduces damage and that mitochondria and the MPT are likely to be involved in the development of hypoglycemic brain damage in the rat.
Tau Cleavage and Dephosphorylation in Cerebellar Granule Neurons Undergoing Apoptosis
Authors: Canu Nadia , Dus Laura , Barbato Christian , Ciotti Maria T. , Brancolini Claudio , Rinaldi Anna M. , Novak Michal , Cattaneo Antonino , Bradbury Andrew , Calissano Pietro 
Published: April 2018

Cerebellar granule cells undergo apoptosis in culture after deprivation of potassium and serum. During this process we found that tau, a neuronal microtubule-associated protein that plays a key role in the maintenance of neuronal architecture, and the pathology of which correlates with intellectual decline in Alzheimer’s disease, is cleaved. The final product of this cleavage is a soluble dephosphorylated tau fragment of 17 kDa that is unable to associate with microtubules and accumulates in the perikarya of dying cells. The appearance of this 17 kDa fragment is inhibited by both caspase and calpain inhibitors, suggesting that tau is anin vivosubstrate for both of these proteases during apoptosis. Tau cleavage is correlated with disruption of the microtubule network, and experiments with colchicine and taxol show that this is likely to be a cause and not a consequence of tau cleavage.These data indicate that tau cleavage and change in phosphorylation are important early factors in the failure of the microtubule network that occurs during neuronal apoptosis. Furthermore, this study introduces new insights into the mechanism(s) that generate the truncated forms of tau present in Alzheimer’s disease.
Intracellular Calcium and Cell Death during Ischemia in Neonatal Rat White Matter AstrocytesIn Situ
Authors: Fern Robert 
Published: April 2018

The major pathological correlate of cerebral palsy is ischemic injury of CNS white matter. Histological studies show early injury of glial cells and axons. To investigate glial cell injury, I monitored intracellular Ca2+and cell viability in fura-2-loaded neonatal rat white matter glial cells during ischemia. Fura-2 fixation combined with immunohistochemistry revealed that fura-2-loaded cells were GFAP+/O4−and were therefore a population of neonatal white matter astrocytes.Significant ischemic Ca2+influx was found, mediated by both L- and T-type voltage-gated Ca2+channels. Ca2+influx via T-type channels was the most important factor during the initial stage of ischemia and was associated with significant cell death within 10–20 min of the onset of ischemia. The Na+–Ca2+exchanger acted to remove cytoplasmic Ca2+throughout the ischemic and recovery periods. Neither the release of Ca2+from intracellular stores nor influx via glutamate-gated channels contributed to the rise in intracellular Ca2+during ischemia. Ischemic cell death was reduced significantly by removing extracellular Ca2+or by blocking voltage-gated Ca2+channels. The exclusively voltage-gated Ca2+channel nature of the Ca2+influx, the role played by T-type Ca2+channels, the protective effect of the Na+–Ca2+exchanger, and the lack of significant Ca2+release from intracellular stores are features of ischemia that have not been reported in other CNS cell types.
Sensory Processing in the Pallium of a Mormyrid Fish
Authors: Prechtl James C. , von der Emde Gerhard , Wolfart Jakob , Karamürsel Saçit , Akoev George N. , Andrianov Yuri N. , Bullock Theodore H. 
Published: April 2018

To investigate the functional organization of higher brain levels in fish we test the hypothesis that the dorsal gray mantle of the telencephalon of a mormyrid fish has discrete receptive areas for several sensory modalities. Multiunit and compound field potentials evoked by auditory, visual, electrosensory, and water displacement stimuli in this weakly electric fish are recorded with multiple semimicroelectrodes placed in many tracks and depths in or near telencephalic area dorsalis pars medialis (Dm).Most responsive loci are unimodal; some respond to two or more modalities. Each modality dominates a circumscribed area, chiefly separate. Auditory and electrical responses cluster in the dorsal 500 μm of rostral and caudolateral Dm, respectively. Two auditory subdivisions underline specialization of this sense. Mechanoreception occupies a caudal area overlapping electroreception but centered 500 μm deeper. Visual responses scatter widely through ventral areas.Auditory, electrosensory, and mechanosensory responses are dominated by a negative wave within the first 50 msec, followed by 15–55 Hz oscillations and a slow positive wave with multiunit spikes lasting from 200 to 500 msec. Stimuli can induce shifts in coherence of certain frequency bands between neighboring loci. Every electric organ discharge command is followed within 3 msec by a large, mainly negative but generally biphasic, widespread corollary discharge. At certain loci large, slow (“δF”) waves usually precede transient shifts in electric organ discharge rate. Sensory-evoked potentials in this fish pallium may be more segregated than in elasmobranchs and anurans and have some surprising similarities to those in mammals.
Cellular and Synaptic Modulation Underlying Substance P-Mediated Plasticity of the Lamprey Locomotor Network
Authors: Parker David , Grillner Sten 
Published: April 2018

The tachykinin substance P modulates the lamprey locomotor network by increasing the frequency of NMDA-evoked ventral root bursts and by making the burst activity more regular. These effects can last in excess of 24 hr. In this paper, the effects of substance P on the synaptic and cellular properties of motor neurons and identified network interneurons have been examined.Substance P potentiated the amplitude of monosynaptic glutamatergic inputs from excitatory interneurons and reticulospinal axons. The amplitude and frequency of miniature EPSPs was increased, suggesting that the synaptic modulation was mediated presynaptically and postsynaptically. The postsynaptic modulation was caused by a specific effect of substance P on the NMDA component of the synaptic input, whereas the presynaptic component was calcium-independent. Substance P did not affect monosynaptic glycinergic inputs from lateral interneurons, crossed inhibitory interneurons, or ipsilateral segmental interneurons or postsynaptic GABAAor GABABresponses, suggesting that it has little effect on inhibitory synaptic transmission.At the cellular level, substance P increased synaptic inputs, resulting in membrane potential oscillations in motor neurons, crossed caudal interneurons, lateral interneurons, and excitatory interneurons. The spiking in response to depolarizing current pulses was increased in motor neurons, lateral interneurons, and excitatory interneurons, but usually was reduced in crossed inhibitory interneurons. Substance P reduced the calcium-dependent afterhyperpolarization after an action potential in motor neurons and lateral interneurons, but did not affect this conductance in excitatory or crossed inhibitory interneurons.The relevance of these cellular and synaptic changes to the modulation of the locomotor network is discussed.
Reexpression of Myogenic Proteins in Mature Electric Organ after Removal of Neural Input
Authors: Unguez Graciela A. , Zakon Harold H. 
Published: April 2018

The electric organ (EO) of the weakly electric fishSternopygus macrurusderives from striated myofibers that fuse and suppress many muscle properties. Mature electrocytes are larger than muscle fibers, do not contain sarcomeres, or express myosin heavy chain (MHC) or tropomyosin. Furthermore, electrocytes express keratin, a protein not expressed in muscle. InS. macrurusthe EO is driven continuously at frequencies higher than those of the intermittently active skeletal muscle. The extent to which differences in EO and muscle phenotype are accounted for by activity patterns, or innervation per se, was determined by assessing the expression of MHC, tropomyosin, and keratin 2 and 5 weeks after the elimination of (1) activity patterns by spinal transection or (2) all synaptic input by denervation.Immunohistochemical analyses showed no changes in muscle fiber phenotypes after either experimental treatment. In contrast, the keratin-positive electrocytes revealed an upregulation of MHC and tropomyosin. Nearly one-third of all electrocytes expressed MHC (35%) and tropomyosin (25%) 2 weeks after spinal transection, whereas approximately two-thirds (61%) expressed MHC 2 weeks after denervation. After 5 weeks of denervation or spinal transection, all electrocytes contained MHC and tropomyosin. Newly formed sarcomere clusters also were observed in denervated electrocytes. The MHC expressed in electrocytes corresponded to that present in a select population of muscle fibers, i.e., type II fibers. Thus, the elimination of electrical activity or all synaptic input resulted in a partial reversal of the electrocyte phenotype to an earlier developmental stage of its myogenic lineage.
Anatomic Evidence of a Three-Dimensional Mosaic Pattern of Tonotopic Organization in the Ventral Complex of the Lateral Lemniscus in Cat
Authors: Malmierca Manuel S. , Leergaard Trygve B. , Bajo Victoria M. , Bjaalie Jan G. , Merchán Miguel A. 
Published: April 2018

The ventral complex of the lateral lemniscus (VCLL, i.e., the ventral and intermediate nuclei) is composed of cells embedded in the fibers of the lateral lemniscus. These cells are involved in the processing of monaural information and receive input from the collaterals of the fibers ascending to the inferior colliculus. Whereas tonotopic organization is a feature of all other nuclei of the auditory system, this functional principle is debated in the VCLL. We have made focal injections of the tracer biotinylated dextran amine into different frequency band representations of the inferior colliculus in cat. Retrogradely labeled cells and terminal fibers (collaterals of efferent local axons and other ascending lemniscal fibers) were found in the ipsilateral VCLL. The spatial distribution of the labeling was analyzed using three-dimensional (3-D) reconstruction and computer graphical visualization techniques. A complex topographic organization was found. In all cases, labeled fibers and cells were distributed in multiple clusters throughout the dorsoventral extent of the VCLL. The shape, size, and location of the labeled clusters suggest an interdigitation of clusters assigned to different frequency-band representations. But an overall mediolateral distribution gradient was observed, with high frequencies represented medially and lower frequencies progressively more laterally.We conclude that the clusters may represent discontinuous frequency-band compartments as a counterpart to the continuous laminar compartments in the remaining auditory nuclei. The 3-D orderly mosaic pattern indicates that the VCLL preserves the spectral decomposition originated in the cochlea in a way that facilitates across-frequency integration.