scholarly journals The transformation of synaptic to system plasticity in motor output from the sacral cord of the adult mouse

2015 ◽  
Vol 114 (3) ◽  
pp. 1987-2004 ◽  
Author(s):  
Mingchen C. Jiang ◽  
Sherif M. Elbasiouny ◽  
William F. Collins ◽  
C. J. Heckman
Keyword(s):  
Synaptic Plasticity ◽  
Adult Mouse ◽  
Motor Output ◽  
Network Activity ◽  
System Level ◽  
Local Network ◽  
System Transformation ◽  
Short Term ◽  
Local Networks

Synaptic plasticity is fundamental in shaping the output of neural networks. The transformation of synaptic plasticity at the cellular level into plasticity at the system level involves multiple factors, including behavior of local networks of interneurons. Here we investigate the synaptic to system transformation for plasticity in motor output in an in vitro preparation of the adult mouse spinal cord. System plasticity was assessed from compound action potentials (APs) in spinal ventral roots, which were generated simultaneously by the axons of many motoneurons (MNs). Synaptic plasticity was assessed from intracellular recordings of MNs. A computer model of the MN pool was used to identify the middle steps in the transformation from synaptic to system behavior. Two input systems that converge on the same MN pool were studied: one sensory and one descending. The two synaptic input systems generated very different motor outputs, with sensory stimulation consistently evoking short-term depression (STD) whereas descending stimulation had bimodal plasticity: STD at low frequencies but short-term facilitation (STF) at high frequencies. Intracellular and pharmacological studies revealed contributions from monosynaptic excitation and stimulus time-locked inhibition but also considerable asynchronous excitation sustained from local network activity. The computer simulations showed that STD in the monosynaptic excitatory input was the primary driver of the system STD in the sensory input whereas network excitation underlies the bimodal plasticity in the descending system. These results provide insight on the roles of plasticity in the monosynaptic and polysynaptic inputs converging on the same MN pool to overall motor plasticity.

scholarly journals Channelrhodopsin variants engage distinct patterns of network activity

2018 ◽  
Author(s):  
Na Young Jun ◽  
Jessica A. Cardin
Keyword(s):  
Network Activity ◽  
Local Network ◽  
Gamma Range ◽  
Cell Type Specific ◽  
Evoked Activity ◽  
Gamma Band Activity ◽  
Circuit Function ◽  
Temporal Profiles

AbstractChannelrhodopsins (ChRs) are light-gated ion channels that enable cell type-specific activation of neurons or neural circuits. Channelrhodopsin-2 has been widely used as a tool to probe circuit function in vitro and in vivo. Several recently developed ChR variants are characterized by faster kinetics and reduced desensitization. However, little is known about how their varying properties may regulate their interaction with local network dynamics. We compared ChR-evoked patterns of multi-unit activity and local field potentials in primary visual cortex of mice expressing three ChR variants with distinct temporal profiles: Chronos, Chrimson, and ChR2. We assessed overall activation of by measuring the amplitude and temporal progression of evoked spiking. Using gamma-range (30-80Hz) LFP power as an assay for local network engagement, we examined the recruitment of cortical network activity by each tool. All ChR variants caused light-evoked increases in firing in vivo, but each demonstrated different temporal patterning of evoked activity. In addition, the three ChRs had distinct effects on cortical gamma-band activity. Our findings suggest that variations in the kinetics of optogenetic tools can substantially affect their efficacy in neural networks in vivo, as well as the manner in which their activation engages circuit resonance.

scholarly journals Differentiation of CD3-4-8- thymocytes in short-term thymic stromal cell culture.

1992 ◽  
Vol 176 (2) ◽  
pp. 543-551 ◽  
Author(s):  
A Sen-Majumdar ◽  
M Lieberman ◽  
S Alpert ◽  
I L Wiessman ◽  
M Small
Keyword(s):  
Culture System ◽  
Stromal Cell ◽  
Adult Mouse ◽  
Culture Period ◽  
Short Term ◽  
Differentiation Potential ◽  
Stromal Cell Culture ◽  
Thymic Stromal Cell

We have investigated the ability of a heterogeneous thymic stromal cell (HTSC) culture system to promote in vitro differentiation of CD3-4-8- thymocytes. Culture of purified murine CD3-4-8- thymocytes on HTSC for 1 d resulted in the appearance of CD4+8+ cells, which did not occur when the sorted cells were maintained in medium alone. It is remarkable that when the culture period was extended to 2 d, CD3-4-8- progenitors differentiated further to CD4+8- and CD4-8+ cells, which also expressed high levels of TCR-CD3. This rapid differentiation on stroma in vitro appears to outpace parallel development in vivo. The differentiation potential of a subset of CD3-4-8- thymocytes that express high levels of a marker of normal and neoplastic thymic progenitors, the 1C11 antigen, was examined next. 1C11hiCD3-4-8- cells also gave rise to CD4-8+ and CD4+8+ populations after 1 d of culture on HTSC. Extending the culture period to 2 d resulted in a significant percentage of CD3-expressing cells that were CD4+8+, CD4+8- and CD4-8+ cells. These results suggest that in the in vitro HTSC culture system, various subsets of immature thymocytes can differentiate into all the mature phenotypes of cells normally found in the adult mouse thymus. This may provide a novel and rapid assay for thymic progenitors.

scholarly journals Effect of adenosine on short-term synaptic plasticity in mouse piriform cortex in vitro: adenosine acts as a high-pass filter

2019 ◽  
Vol 7 (3) ◽  
pp. e13992 ◽  
Author(s):  
Simon P. Perrier ◽  
Marie Gleizes ◽  
Caroline Fonta ◽  
Lionel G. Nowak
Keyword(s):  
Synaptic Plasticity ◽  
Piriform Cortex ◽  
Short Term ◽  
Pass Filter ◽  
High Pass Filter ◽  
High Pass

Microtechnologies for Neurobiology

2010 ◽  
Author(s):  
Henry C. Zeringue
Keyword(s):  
Genetic Programming ◽  
Spatial Information ◽  
Structural Connectivity ◽  
Propagation Delay ◽  
Network Activity ◽  
Local Network ◽  
Oscillatory Activity ◽  
Memory And Attention ◽  
High Level

Oscillatory activity in cortical networks is thought to provide the foundation for many high-level processes including working memory and attention. It has been shown that spatial information propagation delay and connectivity density can determine the innate properties of local network activity. The initial formation of neuronal networks in the central nervous system occurs due to the interaction of the genetic programming of the cells and the presentation of external molecular cues. The activity-driven refinement that occurs later, giving rise to the highly complex networks within the brain, are dependent on the initial anatomical formation and structural connectivity which occurs without external activity cues. We describe technologies used to (1) modulate the genetic programming of neurons and (2) precisely control temporal and spatial presentation of environmental cues in vitro. We are exploring the ability to define simple oscillatory networks using these experimental techniques.

scholarly journals Assessing the Impact of Single-Cell Stimulation on Local Networks in Rat Barrel Cortex—A Feasibility Study

2019 ◽  
Vol 20 (10) ◽  
pp. 2604
Author(s):  
Beate Knauer ◽  
Maik C. Stüttgen
Keyword(s):  
Single Cell ◽  
Statistical Power ◽  
Single Cells ◽  
Network Activity ◽  
Local Network ◽  
Brain State ◽  
Population Activity ◽  
Local Networks ◽  
Cell Stimulation ◽  
The Impact

In contrast to the long-standing notion that the role of individual neurons in population activity is vanishingly small, recent studies have shown that electrical activation of only a single cortical neuron can have measurable effects on global brain state, movement, and perception. Although highly important for understanding how neuronal activity in cortex is orchestrated, the cellular and network mechanisms underlying this phenomenon are unresolved. Here, we first briefly review the current state of knowledge regarding the phenomenon of single-cell induced network modulation and discuss possible underpinnings. Secondly, we show proof of principle for an experimental approach to elucidate the mechanisms of single-cell induced changes in cortical activity. The setup allows simultaneous recordings of the spiking activity of multiple neurons across all layers of the cortex using a multi-electrode array, while manipulating the activity of one individual neuron in close proximity to the array. We demonstrate that single cells can be recorded and stimulated reliably for hundreds of trials, conferring high statistical power even for expectedly small effects of single-neuron spiking on network activity. Preliminary results suggest that single-cell stimulation on average decreases the firing rate of local network units. We expect that characterization of the spatiotemporal spread of single-cell evoked activity across layers and columns will yield novel insights into intracortical processing.

scholarly journals Poly I:C Activated Microglia Disrupt Perineuronal Nets and Modulate Synaptic Balance in Primary Hippocampal Neurons in vitro

2021 ◽  
Vol 13 ◽  
Author(s):  
David Wegrzyn ◽  
Nadja Freund ◽  
Andreas Faissner ◽  
Georg Juckel
Keyword(s):  
Synaptic Plasticity ◽  
Conditioned Medium ◽  
Hippocampal Neurons ◽  
Neuropsychiatric Disorders ◽  
Network Activity ◽  
Poly I:C ◽  
Immunocytochemical Staining ◽  
Perineuronal Nets ◽  
Activated Microglia

Perineuronal nets (PNNs) are specialized, reticular structures of the extracellular matrix (ECM) that can be found covering the soma and proximal dendrites of a neuronal subpopulation. Recent studies have shown that PNNs can highly influence synaptic plasticity and are disrupted in different neuropsychiatric disorders like schizophrenia. Interestingly, there is a growing evidence that microglia can promote the loss of PNNs and contribute to neuropsychiatric disorders. Based on this knowledge, we analyzed the impact of activated microglia on hippocampal neuronal networks in vitro. Therefore, primary cortical microglia were cultured and stimulated via polyinosinic-polycytidylic acid (Poly I:C; 50 μg/ml) administration. The Poly I:C treatment induced the expression and secretion of different cytokines belonging to the CCL- and CXCL-motif chemokine family as well as interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α). In addition, the expression of matrix metalloproteinases (MMPs) could be verified via RT-PCR analysis. Embryonic hippocampal neurons were then cultured for 12 days in vitro (DIV) and treated for 24 h with microglial conditioned medium. Interestingly, immunocytochemical staining of the PNN component Aggrecan revealed a clear disruption of PNNs accompanied by a significant increase of glutamatergic and a decrease of γ-aminobutyric acid-(GABA)ergic synapse numbers on PNN wearing neurons. In contrast, PNN negative neurons showed a significant reduction in both, glutamatergic and GABAergic synapses. Electrophysiological recordings were performed via multielectrode array (MEA) technology and unraveled a significantly increased spontaneous network activity that sustained also 24 and 48 h after the administration of microglia conditioned medium. Taken together, we could observe a strong impact of microglial secreted factors on PNN integrity, synaptic plasticity and electrophysiological properties of cultured neurons. Our observations might enhance the understanding of neuron-microglia interactions considering the ECM.

Ultrastructural investigations of MDL 19,660-induced effects on the canine platelet and megakaryocyte

1990 ◽  
Vol 48 (3) ◽  
pp. 374-375
Author(s):  
D.E. Loudy ◽  
J. Sprinkle-Cavallo ◽  
J.T. Yarrington ◽  
F.Y. Thompson ◽  
J.P. Gibson
Keyword(s):  
Antidepressant Drug ◽  
Beagle Dogs ◽  
Long Term Effects ◽  
Short Term ◽  
Platelet Counts ◽  
Toxicological Studies ◽  
Induced Aggregation ◽  
Internal Architecture

Previous short term toxicological studies of one to two weeks duration have demonstrated that MDL 19,660 (5-(4-chlorophenyl)-2,4-dihydro-2,4-dimethyl-3Hl, 2,4-triazole-3-thione), an antidepressant drug, causes a dose-related thrombocytopenia in dogs. Platelet counts started to decline after two days of dosing with 30 mg/kg/day and continued to decrease to their lowest levels by 5-7 days. The loss in platelets was primarily of the small discoid subpopulation. In vitro studies have also indicated that MDL 19,660: does not spontaneously aggregate canine platelets and has moderate antiaggregating properties by inhibiting ADP-induced aggregation. The objectives of the present investigation of MDL 19,660 were to evaluate ultrastructurally long term effects on platelet internal architecture and changes in subpopulations of platelets and megakaryocytes.Nine male and nine female beagle dogs were divided equally into three groups and were administered orally 0, 15, or 30 mg/kg/day of MDL 19,660 for three months. Compared to a control platelet range of 353,000- 452,000/μl, a doserelated thrombocytopenia reached a maximum severity of an average of 135,000/μl for the 15 mg/kg/day dogs after two weeks and 81,000/μl for the 30 mg/kg/day dogs after one week.

The Effect of Dimethyl Sulfoxide on In Vitro Platelet Function

1976 ◽  
Vol 36 (01) ◽  
pp. 221-229 ◽  
Author(s):  
Charles A. Schiffer ◽  
Caroline L. Whitaker ◽  
Morton Schmukler ◽  
Joseph Aisner ◽  
Steven L. Hilbert
Keyword(s):  
Platelet Count ◽  
Platelet Aggregation ◽  
Dimethyl Sulfoxide ◽  
Platelet Function ◽  
Platelet Volume ◽  
Short Term ◽  
Platelet Factor ◽  
Short Term Exposure ◽  
Structural Abnormalities

SummaryAlthough dimethyl sulfoxide (DMSO) has been used extensively as a cryopreservative for platelets there are few studies dealing with the effect of DMSO on platelet function. Using techniques similar to those employed in platelet cryopreservation platelets were incubated with final concentrations of 2-10% DMSO at 25° C. After exposure to 5 and 10% DMSO platelets remained discoid and electron micrographs revealed no structural abnormalities. There was no significant change in platelet count. In terms of injury to platelet membranes, there was no increased availability of platelet factor-3 or leakage of nucleotides, 5 hydroxytryptamine (5HT) or glycosidases with final DMSO concentrations of 2.5, 5 and 10% DMSO. Thrombin stimulated nucleotide and 5HT release was reduced by 10% DMSO. Impairment of thrombin induced glycosidase release was noted at lower DMSO concentrations and was dose related. Similarly, aggregation to ADP was progressively impaired at DMSO concentrations from 1-5% and was dose related. After the platelets exposed to DMSO were washed, however, aggregation and release returned to control values. Platelet aggregation by epinephrine was also inhibited by DMSO and this could not be corrected by washing the platelets. DMSO-plasma solutions are hypertonic but only minimal increases in platelet volume (at 10% DMSO) could be detected. Shrinkage of platelets was seen with hypertonic solutions of sodium chloride or sucrose suggesting that the rapid transmembrane passage of DMSO prevented significant shifts of water. These studies demonstrate that there are minimal irreversible alterations in in vitro platelet function after short-term exposure to DMSO.

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