scholarly journals Network synchronization and synchrony propagation: emergent elements of inspiration

2019 ◽  
Author(s):  
Sufyan Ashhad ◽  
Jack L Feldman
Keyword(s):  
Spike Activity ◽  
Pattern Generator ◽  
Network Activity ◽  
Network Synchronization ◽  
Brainstem Slice ◽  
Neuronal Interactions ◽  
Motor Nerves ◽  
Output Neurons ◽  
Conductance State

SUMMARYThe preBötzinger Complex (preBötC) – the kernel of breathing rhythmogenesis in mammals – is a non-canonical central pattern generator with undetermined mechanisms. We assessed preBötC network dynamics under respiratory rhythmic and nonrhythmic conditions in vitro. In each cycle under rhythmic conditions, an inspiratory burst emerges as (presumptive) preBötC rhythmogenic neurons transition from aperiodic uncorrelated population spike activity to become increasingly synchronized during preinspiration, triggering bursts; burst activity subsides and the cycle repeats. In a brainstem slice in nonrhythmic conditions, antagonizing GABAA receptors can initiate this periodic synchronization and consequent rhythm coincident with inducing a higher conductance state in nonrhythmogenic preBötC output neurons. Furthermore, when input synchrony onto these neurons was weak, preBötC activity failed to propagate to motor nerves. Our analyses uncover a dynamic reorganization of preBötC network activity – underpinning intricate cyclic neuronal interactions leading to network synchronization and its efficient propagation – correlated with and, we postulate, essential to, rhythmicity.

scholarly journals Interneuron and Pyramidal Cell Interplay During In Vitro Seizure-Like Events

2006 ◽  
Vol 95 (6) ◽  
pp. 3948-3954 ◽  
Author(s):  
Jokubas Ziburkus ◽  
John R. Cressman ◽  
Ernest Barreto ◽  
Steven J. Schiff
Keyword(s):  
Pyramidal Cells ◽  
Network Activity ◽  
Spike Generation ◽  
Cell Pair ◽  
Pathological Conditions ◽  
Neuronal Interactions ◽  
Hippocampal Ca1 ◽  
Cell Type Specific ◽  
Interneuron Activity

Excitatory and inhibitory (EI) interactions shape network activity. However, little is known about the EI interactions in pathological conditions such as epilepsy. To investigate EI interactions during seizure-like events (SLEs), we performed simultaneous dual and triple whole cell and extracellular recordings in pyramidal cells and oriens interneurons in rat hippocampal CA1. We describe a novel pattern of interleaving EI activity during spontaneous in vitro SLEs generated by the potassium channel blocker 4-aminopyridine in the presence of decreased magnesium. Interneuron activity was increased during interictal periods. During ictal discharges interneurons entered into long-lasting depolarization block (DB) with suppression of spike generation; simultaneously, pyramidal cells produced spike trains with increased frequency (6–14 Hz) and correlation. After this period of runaway excitation, interneuron postictal spiking resumed and pyramidal cells became progressively quiescent. We performed correlation measures of cell-pair interactions using either the spikes alone or the subthreshold postsynaptic interspike signals. EE spike correlation was notably increased during interneuron DB, whereas subthreshold EE correlation decreased. EI spike correlations increased at the end of SLEs, whereas II subthreshold correlations increased during DB. Our findings underscore the importance of complex cell-type–specific neuronal interactions in the formation of seizure patterns.

Dementia with Lewy bodies—associated ß-synuclein mutations V70M and P123H cause mutation-specific neuropathological lesions

2021 ◽  
Author(s):  
Maryna Psol ◽  
Sofia Guerin Darvas ◽  
Kristian Leite ◽  
Sameehan U Mahajani ◽  
Mathias Bähr ◽  
...  
Keyword(s):  
Neuronal Network ◽  
Dementia With Lewy Bodies ◽  
Lewy Bodies ◽  
Sporadic Case ◽  
Network Activity ◽  
Proteinase K ◽  
Neuronal Network Activity ◽  
Distinct Disease

Abstract ß-Synuclein (ß-Syn) has long been considered to be an attenuator for the neuropathological effects caused by the Parkinson’s disease-related α-Synuclein (α-Syn) protein. However, recent studies demonstrated that overabundant ß-Syn can form aggregates and induce neurodegeneration in CNS neurons in vitro and in vivo, albeit at a slower pace as compared to α-Syn. Here we demonstrate that ß-Syn mutants V70M, detected in a sporadic case of Dementia with Lewy Bodies (DLB), and P123H, detected in a familial case of DLB, robustly aggravate the neurotoxic potential of ß-Syn. Intriguingly, the two mutations trigger mutually exclusive pathways. ß-Syn V70M enhances morphological mitochondrial deterioration and degeneration of dopaminergic and non-dopaminergic neurons, but has no influence on neuronal network activity. Conversely, ß-Syn P123H silences neuronal network activity, but does not aggravate neurodegeneration. ß-Syn WT, V70M and P123H formed proteinase K (PK) resistant intracellular fibrils within neurons, albeit with less stable C-termini as compared to α-Syn. Under cell free conditions, ß-Syn V70M demonstrated a much slower pace of fibril formation as compared to WT ß-Syn, and P123H fibrils present with a unique phenotype characterized by large numbers of short, truncated fibrils. Thus, it is possible that V70M and P123H cause structural alterations in ß-Syn, that are linked to their distinct neuropathological profiles. The extent of the lesions caused by these neuropathological profiles is almost identical to that of overabundant α-Syn, and thus likely to be directly involved into etiology of DLB. Over all, this study provides insights into distinct disease mechanisms caused by mutations of ß-Syn.

Effect of Common Anesthetics on Dendritic Properties in Layer 5 Neocortical Pyramidal Neurons

2008 ◽  
Vol 99 (3) ◽  
pp. 1394-1407 ◽  
Author(s):  
Sarah Potez ◽  
Matthew E. Larkum
Keyword(s):  
High Frequency ◽  
Pyramidal Neurons ◽  
Animal Experiments ◽  
Apical Dendrite ◽  
Network Activity ◽  
Calcium Spikes ◽  
Firing Properties ◽  
The Impact

Understanding the impact of active dendritic properties on network activity in vivo has so far been restricted to studies in anesthetized animals. However, to date no study has been made to determine the direct effect of the anesthetics themselves on dendritic properties. Here, we investigated the effects of three types of anesthetics commonly used for animal experiments (urethane, pentobarbital and ketamine/xylazine). We investigated the generation of calcium spikes, the propagation of action potentials (APs) along the apical dendrite and the somatic firing properties in the presence of anesthetics in vitro using dual somatodendritic whole cell recordings. Calcium spikes were evoked with dendritic current injection and high-frequency trains of APs at the soma. Surprisingly, we found that the direct actions of anesthetics on calcium spikes were very different. Two anesthetics (urethane and pentobarbital) suppressed dendritic calcium spikes in vitro, whereas a mixture of ketamine and xylazine enhanced them. Propagation of spikes along the dendrite was not significantly affected by any of the anesthetics but there were various changes in somatic firing properties that were highly dependent on the anesthetic. Last, we examined the effects of anesthetics on calcium spike initiation and duration in vivo using high-frequency trains of APs generated at the cell body. We found the same anesthetic-dependent direct effects in addition to an overall reduction in dendritic excitability in anesthetized rats with all three anesthetics compared with the slice preparation.

scholarly journals Btbd11 is an inhibitory interneuron specific synaptic scaffolding protein that supports excitatory synapse structure and function

2021 ◽  
Author(s):  
Alexei M. Bygrave ◽  
Ayesha Sengupta ◽  
Ella P. Jackert ◽  
Mehroz Ahmed ◽  
Beloved Adenuga ◽  
...  
Keyword(s):  
Inhibitory Interneuron ◽  
Nmda Receptor Antagonist ◽  
Specific Protein ◽  
Network Activity ◽  
Scaffolding Protein ◽  
Inhibitory Interneurons ◽  
Cell Type ◽  
Cell Type Specific

Synapses in the brain exhibit cell–type–specific differences in basal synaptic transmission and plasticity. Here, we evaluated cell–type–specific differences in the composition of glutamatergic synapses, identifying Btbd11, as an inhibitory interneuron–specific synapse–enriched protein. Btbd11 is highly conserved across species and binds to core postsynaptic proteins including Psd–95. Intriguingly, we show that Btbd11 can undergo liquid–liquid phase separation when expressed with Psd–95, supporting the idea that the glutamatergic post synaptic density in synapses in inhibitory and excitatory neurons exist in a phase separated state. Knockout of Btbd11 from inhibitory interneurons decreased glutamatergic signaling onto parvalbumin–positive interneurons. Further, both in vitro and in vivo, we find that Btbd11 knockout disrupts network activity. At the behavioral level, Btbd11 knockout from interneurons sensitizes mice to pharmacologically induced hyperactivity following NMDA receptor antagonist challenge. Our findings identify a cell–type–specific protein that supports glutamatergic synapse function in inhibitory interneurons–with implication for circuit function and animal behavior.

scholarly journals Oxytocin shapes spontaneous activity patterns in the developing visual cortex by activating somatostatin interneurons

2019 ◽  
Author(s):  
Paloma P Maldonado ◽  
Alvaro Nuno-Perez ◽  
Jan Kirchner ◽  
Elizabeth Hammock ◽  
Julijana Gjorgjieva ◽  
...  
Keyword(s):  
Visual Cortex ◽  
Spontaneous Activity ◽  
Sensory Processing ◽  
Activity Patterns ◽  
Network Activity ◽  
Synaptic Connections ◽  
Pairwise Correlations ◽  
Early Brain Development

SummarySpontaneous network activity shapes emerging neuronal circuits during early brain development, however how neuromodulation influences this activity is not fully understood. Here, we report that the neuromodulator oxytocin powerfully shapes spontaneous activity patterns. In vivo, oxytocin strongly decreased the frequency and pairwise correlations of spontaneous activity events in visual cortex (V1), but not in somatosensory cortex (S1). This differential effect was a consequence of oxytocin only increasing inhibition in V1 and increasing both inhibition and excitation in S1. The increase in inhibition was mediated by the depolarization and increase in excitability of somatostatin+ (SST) interneurons specifically. Accordingly, silencing SST+ neurons pharmacogenetically fully blocked oxytocin’s effect on inhibition in vitro as well its effect on spontaneous activity patterns in vivo. Thus, oxytocin decreases the excitatory/inhibitory ratio and modulates specific features of V1 spontaneous activity patterns that are crucial for refining developing synaptic connections and sensory processing later in life.

Influence of albumin dialysis (MARS) on neuronal network activity in vitro

2001 ◽  
Vol 39 ◽  
pp. 40-40
Author(s):  
J Loock ◽  
J Stange ◽  
S Mitzner ◽  
R Schmidt ◽  
E W Keefer ◽  
...  
Keyword(s):  
Neuronal Network ◽  
Network Activity ◽  
Albumin Dialysis ◽  
Neuronal Network Activity

scholarly journals Pharmacological intervention to restore connectivity deficits of neuronal networks derived from ASD patient iPSC with a TSC2 mutation

2020 ◽  
Vol 11 (1) ◽  
Author(s):  
Mouhamed Alsaqati ◽  
Vivi M. Heine ◽  
Adrian J. Harwood
Keyword(s):  
Neuronal Network ◽  
Electrode Array ◽  
Network Connectivity ◽  
Autism Spectrum ◽  
Network Activity ◽  
Inhibitory Synapses ◽  
Pharmacological Intervention ◽  
Spatial Connectivity ◽  
Neuronal Network Activity

Abstract Background Tuberous sclerosis complex (TSC) is a rare genetic multisystemic disorder resulting from autosomal dominant mutations in the TSC1 or TSC2 genes. It is characterised by hyperactivation of the mechanistic target of rapamycin complex 1 (mTORC1) pathway and has severe neurodevelopmental and neurological components including autism, intellectual disability and epilepsy. In human and rodent models, loss of the TSC proteins causes neuronal hyperexcitability and synaptic dysfunction, although the consequences of these changes for the developing central nervous system are currently unclear. Methods Here we apply multi-electrode array-based assays to study the effects of TSC2 loss on neuronal network activity using autism spectrum disorder (ASD) patient-derived iPSCs. We examine both temporal synchronisation of neuronal bursting and spatial connectivity between electrodes across the network. Results We find that ASD patient-derived neurons with a functional loss of TSC2, in addition to possessing neuronal hyperactivity, develop a dysfunctional neuronal network with reduced synchronisation of neuronal bursting and lower spatial connectivity. These deficits of network function are associated with elevated expression of genes for inhibitory GABA signalling and glutamate signalling, indicating a potential abnormality of synaptic inhibitory–excitatory signalling. mTORC1 activity functions within a homeostatic triad of protein kinases, mTOR, AMP-dependent protein Kinase 1 (AMPK) and Unc-51 like Autophagy Activating Kinase 1 (ULK1) that orchestrate the interplay of anabolic cell growth and catabolic autophagy while balancing energy and nutrient homeostasis. The mTOR inhibitor rapamycin suppresses neuronal hyperactivity, but does not increase synchronised network activity, whereas activation of AMPK restores some aspects of network activity. In contrast, the ULK1 activator, LYN-1604, increases the network behaviour, shortens the network burst lengths and reduces the number of uncorrelated spikes. Limitations Although a robust and consistent phenotype is observed across multiple independent iPSC cultures, the results are based on one patient. There may be more subtle differences between patients with different TSC2 mutations or differences of polygenic background within their genomes. This may affect the severity of the network deficit or the pharmacological response between TSC2 patients. Conclusions Our observations suggest that there is a reduction in the network connectivity of the in vitro neuronal network associated with ASD patients with TSC2 mutation, which may arise via an excitatory/inhibitory imbalance due to increased GABA-signalling at inhibitory synapses. This abnormality can be effectively suppressed via activation of ULK1.

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