Glutamate Neurotransmission in the Cerebellar Interposed Nuclei: Involvement in Classically Conditioned Eyeblinks and Neuronal Activity

2005 ◽  
Vol 93 (1) ◽  
pp. 44-52 ◽  
Author(s):  
D. P. Aksenov ◽  
N. A. Serdyukova ◽  
J. R. Bloedel ◽  
V. Bracha

The cerebellar interposed nuclei (IN) are critical components of a neural network that controls the expression of classically conditioned eyeblinks. The IN receive 2 major inputs: the massive, γ-aminobutyric acid (GABA)–mediated input from the Purkinje cells of the cerebellar cortex and the relatively weaker, glutamate-mediated input from collaterals of mossy and climbing fiber cerebellar afferent systems. To elucidate the role of IN glutamate neurotransmission in conditioned response (CR) expression, effects of blocking fast glutamatergic neurotransmission in the IN with γ-d-glutamylglycine (DGG) on the expression of conditioned eyeblinks and on cerebellar nuclear neuronal activity were examined. Surprisingly, blocking fast glutamate receptors in the IN did not abolish CRs. DGG decreased CR incidence and slightly increased CR latency. In contrast, identical amounts of DGG applied to the cerebellar cortex abolished CRs. Similar to the behavioral effects, DGG had unexpectedly mild effects on IN neurons. At the population level, the baseline firing frequency of IN cells was not affected. After DGG injections, the incidence of excitatory modulation of cell activity in the interstimulus interval decreased but was not abolished. A combined block of fast glutamate and GABAA neurotransmission using a mixture of DGG and picrotoxin dramatically reduced CR incidence, increased the firing frequency of all cell types, and virtually abolished all modulation of neuronal activity. These results indicate that fast glutamate neurotransmission in the IN plays only an accessory role both in the expression of behavioral CRs and in the generation of associated neuronal activity in the IN.

2017 ◽  
Vol 372 (1715) ◽  
pp. 20160161 ◽  
Author(s):  
Claudia Clopath ◽  
Tobias Bonhoeffer ◽  
Mark Hübener ◽  
Tobias Rose

The brain extracts behaviourally relevant sensory input to produce appropriate motor output. On the one hand, our constantly changing environment requires this transformation to be plastic. On the other hand, plasticity is thought to be balanced by mechanisms ensuring constancy of neuronal representations in order to achieve stable behavioural performance. Yet, prominent changes in synaptic strength and connectivity also occur during normal sensory experience, indicating a certain degree of constitutive plasticity. This raises the question of how stable neuronal representations are on the population level and also on the single neuron level. Here, we review recent data from longitudinal electrophysiological and optical recordings of single-cell activity that assess the long-term stability of neuronal stimulus selectivities under conditions of constant sensory experience, during learning, and after reversible modification of sensory input. The emerging picture is that neuronal representations are stabilized by behavioural relevance and that the degree of long-term tuning stability and perturbation resistance directly relates to the functional role of the respective neurons, cell types and circuits. Using a ‘toy’ model, we show that stable baseline representations and precise recovery from perturbations in visual cortex could arise from a ‘backbone’ of strong recurrent connectivity between similarly tuned cells together with a small number of ‘anchor’ neurons exempt from plastic changes. This article is part of the themed issue ‘Integrating Hebbian and homeostatic plasticity’.


1992 ◽  
Vol 67 (3) ◽  
pp. 599-609 ◽  
Author(s):  
A. J. Tierney ◽  
R. M. Harris-Warrick

1. Our experiments were performed to assess the quantitative role of the transient potassium current, IA, in determining the cycle frequency and phasing of neurons in the network generating the pyloric motor rhythm in the stomatogastric ganglion of the spiny lobster, Panulirus interruptus. We used 4-aminopyridine (4-AP) to reduce IA and recorded the effects of this treatment on cell activity. 2. In the intact circuit with an actively cycling pyloric rhythm, 4-AP had three major effects on the rhythm. First, the cycle period was decreased approximately 20%. Second, 4-AP enhanced the activity of all cells, causing increases in spikes/burst and spike frequency within bursts. Third, 4-AP altered the phasing of follower cells relative to the onset of the pacemaker (AB/PD) bursts. The lateral pyloric (LP) and pylorics (PYs) were phase advanced by 4-AP, whereas the ventral dilator (VD) was phase delayed. 3. Voltage-clamp studies indicated that pyloric cells differed in the amount of IA they expressed on or near the soma. IA was largest in pyloric dilator (PD) and PY cells, smaller in the anterior burster (AB), LP, and inferior cardiac (IC) cells, and undetectable in the VD cell. When cells were isolated from synaptic input, however, all were excited by 4-AP, suggesting that all possess functionally significant IA. In VD cells, IA-like currents probably occur primarily in nonsomatic cell regions. 4. We measured postinhibitory rebound by determining the delay to the first spike after a series of 200-ms hyperpolarizing prepulses in the PD, PY, LP, VD, and IC cells. In all five cell types, the delay was progressively increased as the potential of the hyperpolarizing prepulse became more negative. This increased delay reflected the removal of IA inactivation. The delay was greatest in the PY cell and least in the IC. In four cells (the PD, PY, LP, and VD) 4-AP decreased the delay to the first spike at all prepulse potentials. In the IC the delay to the first spike was unaffected by 4-AP, suggesting that IA was not responsible for the relatively short delay after hyperpolarizing prepulses. 5. In all five cell types, 4-AP increased the spike frequency for the duration of a 1-s depolarization. The 4-AP-sensitive current responsible for this behavior appears to have very rapid kinetics and may represent a distinct channel subtype. Functionally, this current may act to dampen cell excitability and to reduce spike frequency during bursts.


2021 ◽  
Vol 2021 ◽  
pp. 1-11
Author(s):  
Yunyun Qu ◽  
Xin Liu ◽  
Shuai Zong ◽  
Huanxin Sun ◽  
Shuang Liu ◽  
...  

Protocatechualdehyde (PCA), an important component of Salvia miltiorrhiza, has many activities, such as anti-inflammatory and antisepsis activities. However, the role of PCA in osteoclasts is not clear. We used RAW264.7 cells (a mouse leukemic monocyte/macrophage cell line) and bone marrow macrophages (BMMs) to probe the role of PCA in osteoclasts and the underlying mechanism. The effects of PCA on cell activity were evaluated with CCK-8 assays. TRAP staining detected mature osteoclasts. Corning Osteo Assay Surface plates were used to examine absorption. The levels of RNA and protein were analyzed, respectively, using RT-PCR and Western blotting. PCA (5 μg/ml) was not toxic to the two cell types but reduced the formation of osteoclasts and bone absorption. Furthermore, PCA restrained the expression of mRNAs encoding proteins associated with osteoclasts and reduced the phosphorylation of proteins in important signaling pathways. The results indicate that PCA inhibits osteoclast differentiation by suppressing NF-κB and MAPK activity.


2004 ◽  
Vol 16 (4) ◽  
pp. 673-715 ◽  
Author(s):  
Eric Brown ◽  
Jeff Moehlis ◽  
Philip Holmes

We undertake a probabilistic analysis of the response of repetitively firing neural populations to simple pulselike stimuli. Recalling and extending results from the literature, we compute phase response curves (PRCs) valid near bifurcations to periodic firing for Hindmarsh-Rose, Hodgkin-Huxley, Fitz Hugh-Nagumo, and Morris-Lecar models, encompassing the four generic (codimension one) bifurcations. Phase density equations are then used to analyze the role of the bifurcation, and the resulting PRC, in responses to stimuli. In particular, we explore the interplay among stimulus duration, baseline firing frequency, and population-level response patterns. We interpret the results in terms of the signal processing measure of gain and discuss further applications and experimentally testable predictions.


2018 ◽  
Vol 2018 ◽  
pp. 1-9 ◽  
Author(s):  
Esmaeil Mortaz ◽  
Saeede Amani ◽  
Sharon Mumby ◽  
Ian M. Adcock ◽  
Mehrnaz Movassaghi ◽  
...  

The multifunctional role of mast cells (MCs) in the immune system is complex and has not fully been explored. MCs reside in tissues and mucous membranes such as the lung, digestive tract, and skin which are strategically located at interfaces with the external environment. These cells, therefore, will encounter external stimuli and pathogens. MCs modulate both the innate and the adaptive immune response in inflammatory disorders including transplantation. MCs can have pro- and anti-inflammatory functions, thereby regulating the outcome of lung transplantation through secretion of mediators that allow interaction with other cell types, particularly innate lymphoid cells (ILC2). ILC2 cells are a unique population of hematopoietic cells that coordinate the innate immune response against a variety of threats including infection, tissue damage, and homeostatic disruption. In addition, MCs can modulate alloreactive T cell responses or assist in T regulatory (Treg) cell activity. This paper outlines the current understanding of the role of MCs in lung transplantation, with a specific focus on their interaction with ILC2 cells within the engrafted organ.


2017 ◽  
Author(s):  
Georgia M. Alexander ◽  
Logan Y. Brown ◽  
Shannon Farris ◽  
Daniel Lustberg ◽  
Caroline Pantazis ◽  
...  

AbstractHippocampal oscillations arise from coordinated activity among distinct populations of neurons and are associated with cognitive functions and behaviors. Although much progress has been made toward identifying the relative contribution of specific neuronal populations in hippocampal oscillations, far less is known about the role of hippocampal area CA2, which is thought to support social aspects of episodic memory. Furthermore, the little existing evidence on the role of CA2 in oscillations has led to conflicting conclusions. Therefore, we sought to identify the specific contribution of CA2 pyramidal neurons to brain oscillations using a controlled experimental system. We used excitatory and inhibitory DREADDs in transgenic mice to acutely and reversibly manipulate CA2 pyramidal cell activity. Here, we report on the role of CA2 in hippocampal-prefrontal cortical network oscillations and social behavior. We found that excitation or inhibition of CA2 pyramidal cells bidirectionally regulated hippocampal and prefrontal cortical low gamma oscillations and inversely modulated hippocampal ripple oscillations. Further, CA2 inhibition impaired social approach behavior. These findings support a role for CA2 in low gamma generation and ripple modulation within the hippocampus and underscore the importance of CA2 neuronal activity in extrahippocampal oscillations and social behavior.


1999 ◽  
Vol 81 (2) ◽  
pp. 835-844 ◽  
Author(s):  
Iran Salimi ◽  
Thomas Brochier ◽  
Allan M. Smith

Neuronal activity in somatosensory cortex of monkeys using a precision grip. II. Responses to object texture and weights. Three monkeys were trained to lift and hold a test object within a 12- to 25-mm position window for 1 s. The activity of single neurons was recorded during performance of the task in which both the weight and surface texture of the object were systematically varied. Whenever possible, each cell was tested with three weights (15, 65, and 115 g) and three textures (smooth metal, fine 200 grit sandpaper, and rough 60 grit sandpaper). Of 386 cells recorded in 3 monkeys, 45 cells had cutaneous receptive fields on the index or thumb or part of the thenar eminence and were held long enough to be tested in all 9 combinations of texture and weight. Recordings were made for the entire anterior-posterior extent of the thumb and index finger areas in somatosensory cortex including area 7b. However, the statistical analysis required a selection of only those cells for which nine complete recording conditions were available limiting the sample to cells in areas 2, 5, and 7b. Significant differences in the grip force accompanied 98% of the changes in texture and 78% of the changes in weight. Increasing the object weight also increased the force tangential to the skin surface as measured by the load or lifting force. The peak discharge during lifting was judged to be the most sensitive index of cell activity and was analyzed with a two-way analysis of variance (ANOVA). In addition, peak cell discharge was normalized to allow comparisons among different combinations of texture and weight as well as comparisons among different neurons. Overall, the peak firing frequency of 87% of the cells was significantly modulated by changes in object texture, but changes in object weight affected the peak activity of only 58% of the cells. Almost all (17/18, 94%) of the static cells were influenced by the object texture, and 81% of the dynamic cells that were active only briefly at grip and lift onset were modulated by texture. For some cells, surface texture had a significant effect on neuronal discharge that was independent of the object weight. In contrast, weight-related responses were never simple main effects of the weight alone and appeared instead as significant interactions between texture and weight. Four neurons either increased or decreased activity in a graded fashion with surface structure (roughness) regardless of the object weight ( P < 0.05). Ten other neurons showed increases or decreases in response to one or two textures, which might represent either a graded response or a tuning preference for a specific texture. The firing frequency of the majority (31/45) of neurons reflected an interaction of both texture and weight. The cells with texture-related but weight-independent activities were thought to encode surface characteristics that are largely independent of the grip and lifting forces used to manipulate the object. Such constancies could be used to construct internal representations or mental models for planning and controlling object manipulation.


Author(s):  
W.T. Gunning ◽  
M.R. Marino ◽  
M.S. Babcock ◽  
G.D. Stoner

The role of calcium in modulating cellular replication and differentiation has been described for various cell types. In the present study, the effects of Ca++ on the growth and differentiation of cultured rat esophageal epithelial cells was investigated.Epithelial cells were isolated from esophagi taken from 8 week-old male CDF rats by the enzymatic dissociation method of Kaighn. The cells were cultured in PFMR-4 medium supplemented with 0.25 mg/ml dialyzed fetal bovine serum, 5 ng/ml epidermal growth factor, 10-6 M hydrocortisone 10-6 M phosphoethanolamine, 10-6 M ethanolamine, 5 pg/ml insulin, 5 ng/ml transferrin, 10 ng/ml cholera toxin and 50 ng/ml garamycin at 36.5°C in a humidified atmosphere of 3% CO2 in air. At weekly intervals, the cells were subcultured with a solution containing 1% polyvinylpyrrolidone, 0.01% EGTA, and 0.05% trypsin. After various passages, the replication rate of the cells in PFMR-4 medium containing from 10-6 M to 10-3 M Ca++ was determined using a clonal growth assay.


Author(s):  
A.J. Mia ◽  
L.X. Oakford ◽  
T. Yorio

Protein kinase C (PKC) isozymes, when activated, are translocated to particulate membrane fractions for transport to the apical membrane surface in a variety of cell types. Evidence of PKC translocation was demonstrated in human megakaryoblastic leukemic cells, and in cardiac myocytes and fibroblasts, using FTTC immunofluorescent antibody labeling techniques. Recently, we reported immunogold localizations of PKC subtypes I and II in toad urinary bladder epithelia, following 60 min stimulation with Mezerein (MZ), a PKC activator, or antidiuretic hormone (ADH). Localization of isozyme subtypes I and n was carried out in separate grids using specific monoclonal antibodies with subsequent labeling with 20nm protein A-gold probes. Each PKC subtype was found to be distributed singularly and in discrete isolated patches in the cytosol as well as in the apical membrane domains. To determine if the PKC isozymes co-localized within the cell, a double immunogold labeling technique using single grids was utilized.


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