Inhibitory Modulation of Cortical Up States

2010 ◽  
Vol 104 (3) ◽  
pp. 1314-1324 ◽  
Author(s):  
Maria V. Sanchez-Vives ◽  
Maurizio Mattia ◽  
Albert Compte ◽  
Maria Perez-Zabalza ◽  
Milena Winograd ◽  
...  
Keyword(s):  
Slow Wave Sleep ◽  
Epileptiform Activity ◽  
Local Network ◽  
Similar Frequency ◽  
Inhibitory Modulation ◽  
State Duration ◽  
Up States ◽  
Activity Dependent ◽  
Different Levels

The balance between excitation and inhibition is critical in the physiology of the cerebral cortex. To understand the influence of inhibitory control on the emergent activity of the cortical network, inhibition was progressively blocked in a slice preparation that generates spontaneous rhythmic up states at a similar frequency to those occurring in vivo during slow-wave sleep or anesthesia. Progressive removal of inhibition induced a parametric shortening of up state duration and elongation of the down states, the frequency of oscillations decaying. Concurrently, a gradual increase in the network firing rate during up states occurred. The slope of transitions between up and down states was quantified for different levels of inhibition. The slope of upward transitions reflects the recruitment of the local network and was progressively increased when inhibition was decreased, whereas the speed of activity propagation became faster. Removal of inhibition eventually resulted in epileptiform activity. Whereas gradual reduction of inhibition induced linear changes in up/down states and their propagation, epileptiform activity was the result of a nonlinear transformation. A computational network model showed that strong recurrence plus activity-dependent hyperpolarizing currents were sufficient to account for the observed up state modulations and predicted an increase in activity-dependent hyperpolarization following up states when inhibition was decreased, which was confirmed experimentally.

scholarly journals Activity-Dependent Downscaling of Subthreshold Synaptic Inputs during Slow-Wave-Sleep-like Activity In Vivo

Neuron ◽  
2018 ◽  
Vol 97 (6) ◽  
pp. 1244-1252.e5 ◽  
Author(s):  
Ana González-Rueda ◽  
Victor Pedrosa ◽  
Rachael C. Feord ◽  
Claudia Clopath ◽  
Ole Paulsen
Keyword(s):  
Slow Wave ◽  
Slow Wave Sleep ◽  
Synaptic Inputs ◽  
Activity Dependent

Extracellular pH Responses in CA1 and the Dentate Gyrus During Electrical Stimulation, Seizure Discharges, and Spreading Depression

2000 ◽  
Vol 83 (6) ◽  
pp. 3519-3524 ◽  
Author(s):  
Zhi-Qi Xiong ◽  
Janet L. Stringer
Keyword(s):  
Dentate Gyrus ◽  
Spreading Depression ◽  
Seizure Activity ◽  
Epileptiform Activity ◽  
Extracellular Ph ◽  
Extracellular Acidification ◽  
Ca1 Region ◽  
Activity Dependent

Since neuronal excitability is sensitive to changes in extracellular pH and there is regional diversity in the changes in extracellular pH during neuronal activity, we examined the activity-dependent extracellular pH changes in the CA1 region and the dentate gyrus. In vivo, in the CA1 region, recurrent epileptiform activity induced by stimulus trains, bicuculline, and kainic acid resulted in biphasic pH shifts, consisting of an initial extracellular alkalinization followed by a slower acidification. In vitro, stimulus trains also evoked biphasic pH shifts in the CA1 region. However, in CA1, seizure activity in vitro induced in the absence of synaptic transmission, by perfusing with 0 Ca2+/5 mM K+medium, was only associated with extracellular acidification. In the dentate gyrus in vivo, seizure activity induced by stimulation to the angular bundle or by injection of either bicuculline or kainic acid was only associated with extracellular acidification. In vitro, stimulus trains evoked only acidification. In the dentate gyrus in vitro, recurrent epileptiform activity induced in the absence of synaptic transmission by perfusion with 0 Ca2+/8 mM K+medium was associated with extracellular acidification. To test whether glial cell depolarization plays a role in the regulation of the extracellular pH, slices were perfused with 1 mM barium. Barium increased the amplitude of the initial alkalinization in CA1 and caused the appearance of alkalinization in the dentate gyrus. In both CA1 and the dentate gyrus in vitro, spreading depression was associated with biphasic pH shifts. These results demonstrate that activity-dependent extracellular pH shifts differ between CA1 and dentate gyrus both in vivo and in vitro. The differences in pH fluctuations with neuronal activity might be a marker for the basis of the regional differences in seizure susceptibility between CA1 and the dentate gyrus.

scholarly journals Up and Down States During Slow Oscillations in Slow-Wave Sleep and Different Levels of Anesthesia

2021 ◽  
Vol 15 ◽  
Author(s):  
Melody Torao-Angosto ◽  
Arnau Manasanch ◽  
Maurizio Mattia ◽  
Maria V. Sanchez-Vives
Keyword(s):  
Slow Wave ◽  
Small Area ◽  
Slow Wave Sleep ◽  
Dynamic Regime ◽  
Network Activity ◽  
Oscillatory Regime ◽  
Slow Oscillations ◽  
State Duration ◽  
Up And Down States ◽  
Different Levels

Slow oscillations are a pattern of synchronized network activity generated by the cerebral cortex. They consist of Up and Down states, which are periods of activity interspersed with periods of silence, respectively. However, even when this is a unique dynamic regime of transitions between Up and Down states, this pattern is not constant: there is a range of oscillatory frequencies (0.1–4 Hz), and the duration of Up vs. Down states during the cycles is variable. This opens many questions. Is there a constant relationship between the duration of Up and Down states? How much do they vary across conditions and oscillatory frequencies? Are there different sub regimes within the slow oscillations? To answer these questions, we aimed to explore a concrete aspect of slow oscillations, Up and Down state durations, across three conditions: deep anesthesia, light anesthesia, and slow-wave sleep (SWS), in the same chronically implanted rats. We found that light anesthesia and SWS have rather similar properties, occupying a small area of the Up and Down state duration space. Deeper levels of anesthesia occupy a larger region of this space, revealing that a large variety of Up and Down state durations can emerge within the slow oscillatory regime. In a network model, we investigated the network parameters that can explain the different points within our bifurcation diagram in which slow oscillations are expressed.

Antimicrobial and antibiofilm activities of meropenem loaded-mesoporous silica nanoparticles against carbapenem-resistant Pseudomonas aeruginosa

2021 ◽  
pp. 088532822110038
Author(s):  
Mohammad Yousef Memar ◽  
Mina Yekani ◽  
Hadi Ghanbari ◽  
Edris Nabizadeh ◽  
Sepideh Zununi Vahed ◽  
...  
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Mesoporous Silica ◽  
Silica Nanoparticles ◽  
Mesoporous Silica Nanoparticles ◽  
Carbapenem Resistant ◽  
Toxicity In Vitro ◽  
Different Levels

The aims of the present study were the determination of antimicrobial and antibiofilm effects of meropenem-loaded mesoporous silica nanoparticles (MSNs) on carbapenem resistant Pseudomonas aeruginosa ( P. aeruginosa) and cytotoxicity properties in vitro. The meropenem-loaded MSNs had shown antibacterial and biofilm inhibitory activities on all isolates at different levels lower than MICs and BICs of meropenem. The viability of HC-04 cells treated with serial concentrations as MICs and BICs of meropenem-loaded MSNs was 92–100%. According to the obtained results, meropenem-loaded MSNs display the significant antibacterial and antibiofilm effects against carbapenem resistant and biofilm forming P. aeruginosa and low cell toxicity in vitro. Then, the prepared system can be an appropriate option for the delivery of carbapenem for further evaluation in vivo assays.

Extracellular Release of ILEI/FAM3C and Amyloid-β Is Associated with the Activation of Distinct Synapse Subpopulations

2021 ◽  
pp. 1-16
Author(s):  
Masaki Nakano ◽  
Yachiyo Mitsuishi ◽  
Lei Liu ◽  
Naoki Watanabe ◽  
Emi Hibino ◽  
...  
Keyword(s):  
Neuronal Activity ◽  
Epithelial Mesenchymal Transition ◽  
Surrogate Marker ◽  
Amyloid Β ◽  
Dependent Manner ◽  
Mesenchymal Transition ◽  
Extracellular Release ◽  
Activity Dependent ◽  
Aβ Production

Background: Brain amyloid-β (Aβ) peptide is released into the interstitial fluid (ISF) in a neuronal activity-dependent manner, and Aβ deposition in Alzheimer’s disease (AD) is linked to baseline neuronal activity. Although the intrinsic mechanism for Aβ generation remains to be elucidated, interleukin-like epithelial-mesenchymal transition inducer (ILEI) is a candidate for an endogenous Aβ suppressor. Objective: This study aimed to access the mechanism underlying ILEI secretion and its effect on Aβ production in the brain. Methods: ILEI and Aβ levels in the cerebral cortex were monitored using a newly developed ILEI-specific ELISA and in vivo microdialysis in mutant human Aβ precursor protein-knockin mice. ILEI levels in autopsied brains and cerebrospinal fluid (CSF) were measured using ELISA. Results: Extracellular release of ILEI and Aβ was dependent on neuronal activation and specifically on tetanus toxin-sensitive exocytosis of synaptic vesicles. However, simultaneous monitoring of extracellular ILEI and Aβ revealed that a spontaneous fluctuation of ILEI levels appeared to inversely mirror that of Aβ levels. Selective activation and inhibition of synaptic receptors differentially altered these levels. The evoked activation of AMPA-type receptors resulted in opposing changes to ILEI and Aβ levels. Brain ILEI levels were selectively decreased in AD. CSF ILEI concentration correlated with that of Aβ and were reduced in AD and mild cognitive impairment. Conclusion: ILEI and Aβ are released from distinct subpopulations of synaptic terminals in an activity-dependent manner, and ILEI negatively regulates Aβ production in specific synapse types. CSF ILEI might represent a surrogate marker for the accumulation of brain Aβ.

scholarly journals Dynamic modulation of spike timing-dependent calcium influx during corticostriatal upstates

2013 ◽  
Vol 110 (7) ◽  
pp. 1631-1645 ◽  
Author(s):  
R. C. Evans ◽  
Y. M. Maniar ◽  
K. T. Blackwell
Keyword(s):  
Synaptic Plasticity ◽  
Slow Wave Sleep ◽  
Calcium Influx ◽  
Spike Timing ◽  
Medium Spiny Neuron ◽  
Calcium Transients ◽  
Biophysical Model ◽  
Published Data ◽  
High Calcium

The striatum of the basal ganglia demonstrates distinctive upstate and downstate membrane potential oscillations during slow-wave sleep and under anesthetic. The upstates generate calcium transients in the dendrites, and the amplitude of these calcium transients depends strongly on the timing of the action potential (AP) within the upstate. Calcium is essential for synaptic plasticity in the striatum, and these large calcium transients during the upstates may control which synapses undergo plastic changes. To investigate the mechanisms that underlie the relationship between calcium and AP timing, we have developed a realistic biophysical model of a medium spiny neuron (MSN). We have implemented sophisticated calcium dynamics including calcium diffusion, buffering, and pump extrusion, which accurately replicate published data. Using this model, we found that either the slow inactivation of dendritic sodium channels (NaSI) or the calcium inactivation of voltage-gated calcium channels (CDI) can cause high calcium corresponding to early APs and lower calcium corresponding to later APs. We found that only CDI can account for the experimental observation that sensitivity to AP timing is dependent on NMDA receptors. Additional simulations demonstrated a mechanism by which MSNs can dynamically modulate their sensitivity to AP timing and show that sensitivity to specifically timed pre- and postsynaptic pairings (as in spike timing-dependent plasticity protocols) is altered by the timing of the pairing within the upstate. These findings have implications for synaptic plasticity in vivo during sleep when the upstate-downstate pattern is prominent in the striatum.

scholarly journals The thalamic low-threshold Ca 2+ potential: a key determinant of the local and global dynamics of the slow (<1 Hz) sleep oscillation in thalamocortical networks

2011 ◽  
Vol 369 (1952) ◽  
pp. 3820-3839 ◽  
Author(s):  
Vincenzo Crunelli ◽  
Adam C. Errington ◽  
Stuart W. Hughes ◽  
Tibor I. Tóth
Keyword(s):  
Action Potential ◽  
Slow Oscillation ◽  
Global Dynamics ◽  
Action Potential Firing ◽  
Local And Global Dynamics ◽  
Up States ◽  
Potential Firing ◽  
Low Threshold

During non-rapid eye movement sleep and certain types of anaesthesia, neurons in the neocortex and thalamus exhibit a distinctive slow (<1 Hz) oscillation that consists of alternating UP and DOWN membrane potential states and which correlates with a pronounced slow (<1 Hz) rhythm in the electroencephalogram. While several studies have claimed that the slow oscillation is generated exclusively in neocortical networks and then transmitted to other brain areas, substantial evidence exists to suggest that the full expression of the slow oscillation in an intact thalamocortical (TC) network requires the balanced interaction of oscillator systems in both the neocortex and thalamus. Within such a scenario, we have previously argued that the powerful low-threshold Ca 2+ potential (LTCP)-mediated burst of action potentials that initiates the UP states in individual TC neurons may be a vital signal for instigating UP states in related cortical areas. To investigate these issues we constructed a computational model of the TC network which encompasses the important known aspects of the slow oscillation that have been garnered from earlier in vivo and in vitro experiments. Using this model we confirm that the overall expression of the slow oscillation is intricately reliant on intact connections between the thalamus and the cortex. In particular, we demonstrate that UP state-related LTCP-mediated bursts in TC neurons are proficient in triggering synchronous UP states in cortical networks, thereby bringing about a synchronous slow oscillation in the whole network. The importance of LTCP-mediated action potential bursts in the slow oscillation is also underlined by the observation that their associated dendritic Ca 2+ signals are the only ones that inform corticothalamic synapses of the TC neuron output, since they, but not those elicited by tonic action potential firing, reach the distal dendritic sites where these synapses are located.

scholarly journals Epileptiform Discharges With In-Vivo-Like Features in Slices of Rat Piriform Cortex With Longitudinal Association Fibers

2001 ◽  
Vol 86 (5) ◽  
pp. 2445-2460 ◽  
Author(s):  
Rezan Demir ◽  
Lewis B. Haberly ◽  
Meyer B. Jackson
Keyword(s):  
Seizure Activity ◽  
Epileptiform Activity ◽  
Piriform Cortex ◽  
Brain Slices ◽  
Epileptiform Discharges ◽  
Local Circuitry ◽  
Association Fibers ◽  
Discharge Propagation

Brain slices serve as useful models for the investigation of epilepsy. However, the preparation of brain slices disrupts circuitry and severs axons, thus complicating efforts to relate epileptiform activity in vitro to seizure activity in vivo. This issue is relevant to studies in transverse slices of the piriform cortex (PC), the preparation of which disrupts extensive rostrocaudal fiber systems. In these slices, epileptiform discharges propagate slowly and in a wavelike manner, whereas such discharges in vivo propagate more rapidly and jump abruptly between layers. The objective of the present study was to identify fiber systems responsible for these differences. PC slices were prepared by cutting along three different nearly orthogonal planes (transverse, parasagittal, and longitudinal), and epileptiform discharges were imaged with a voltage-sensitive fluorescent dye. Interictal-like epileptiform activity was enabled by either a kindling-like induction process or disinhibition with bicuculline. The pattern of discharge onset was very similar in slices cut in different planes. As described previously in transverse PC slices, discharges were initiated in the endopiriform nucleus (En) and adjoining regions in a two-stage process, starting with low-amplitude “plateau activity” at one site and leading to an accelerating depolarization and discharge onset at another nearby site. The similar pattern of onset in slices of various orientations indicates that the local circuitry and neuronal properties in and around the En, rather than long-range fibers, assume dominant roles in the initiation of epileptiform activity. Subtle variations in the onset site indicate that interneurons can fine tune the site of discharge onset. In contrast to the mode of onset, discharge propagation showed striking variations. In longitudinal slices, where rostrocaudal association fibers are best preserved, discharge propagation resembled in vivo seizure activity in the following respects: propagation was as rapid as in vivo and about two to three times faster than in other slices; discharges jumped abruptly between the En and PC; and discharges had large amplitudes in superficial layers of the PC. Cuts in longitudinal slices that partially separated the PC from the En eliminated these unique features. These results help clarify why epileptiform activity differs between in vitro and in vivo experiments and suggest that rostrocaudal pyramidal cell association fibers play a major role in the propagation of discharges in the intact brain. The longitudinal PC slice, which best preserves these fibers, is ideally suited for the study their role.

scholarly journals In vitro life cycle of pentamidine-resistant amastigotes: stability of the chemoresistant phenotypes is dependent on the level of resistance induced.

1997 ◽  
Vol 41 (9) ◽  
pp. 1898-1903 ◽  
Author(s):  
D Sereno ◽  
J L Lemesre
Keyword(s):  
Life Cycle ◽  
Culture Conditions ◽  
Cross Resistance ◽  
Diminazene Aceturate ◽  
Drug Pressure ◽  
Mouse Macrophages ◽  
Wild Type Clone ◽  
Different Levels

Using a continuous drug pressure protocol, we induced pentamidine resistance in an active and dividing population of amastigote forms of Leishmania mexicana. We selected in vitro two clones with different levels of resistance to pentamidine, with clone LmPENT5 being resistant to 5 microM pentamidine, while clone LmPENT20 was resistant to 20 microM pentamidine. Resistance indexes (50% inhibitory concentration [IC50] after drug presure/IC50 before drug pressure) of 2 (LmPENT5) and 6 (LmPENT20) were determined after drug selection. Both resistant clones expressed significant cross-resistance to diminazene aceturate and primaquine. Pentamidine resistance was not reversed by verapamil, a calcium channel blocker known to reverse multidrug resistance (A. J. Bitonti, et al., Science 242:1301-1303, 1988; A. R. C. Safa et al., J. Biol. Chem. 262:7884-7888, 1987). No difference in the in vitro infectivity for resident mouse macrophages was observed between the wild-type clone (clone LmWT) and pentamidine-resistant clones. During in vitro infectivity experiments, when the life cycle was performed starting from the intramacrophagic amastigote stage, the drug resistance of the resulting LmPENT20 amastigotes was preserved even if the intermediate promastigote stage could not be considered resistant to 20 microM pentamidine. In the same way, when a complete developmental sequence of L. mexicana was achieved axenically by manipulation of appropriate culture conditions, the resulting axenically grown LmPENT20 amastigotes remained pentamidine resistant, whereas LmPENT5 amastigotes lost their ability to resist pentamidine, with IC50s and index of resistance values close to those for the LmWT clone. These results strongly indicate that the level of pentamidine tolerated by resistant amastigotes after the life cycle was dependent on the induced level of resistance. This fact could be significant in the in vivo transmission of drug-resistant parasites by Phlebotominae. Particular attention should be given to the finding that the emergence of parasite resistance is a potential risk of the use of inadequate doses as therapy in humans.

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