Spike Bursts Research Articles

Effect of burst spikes on linear and nonlinear signal transmission in spiking neurons.

We study the impact of bursts on spike statistics and neural signal transmission. We propose a stochastic burst algorithm that is applied to a burst-free spike train and adds a random number of temporally-jittered burst spikes to each spike. This simple algorithm ignores any possible stimulus-dependence of bursting but allows to relate spectra and signal-transmission characteristics of burst-free and burst-endowed spike trains. By averaging over the various statistical ensembles, we find a frequency-dependent factor connecting the linear and also the second-order susceptibility of the spike trains with and without bursts. The relation between spectra is more complicated: besides a frequency-dependent multiplicative factor it also involves an additional frequency-dependent offset. We confirm these relations for the (burst-free) spike trains of a stochastic integrate-and-fire neuron and identify frequency ranges in which the transmission is boosted or diminished by bursting. We then consider bursty spike trains of electroreceptor afferents of weakly electric fish and approach the role of burst spikes as follows. We compare the spectral statistics of the bursty spike train to (i) that of a spike train with burst spikes removed and to (ii) that of the spike train in (i) endowed by bursts according to our algorithm. Significant spectral features are explained by our signal-independent burst algorithm, e.g. the burst-induced boosting of the nonlinear response. A difference is seen in the information transfer for the original bursty spike train and our burst-endowed spike train. Our algorithm is thus helpful to identify different effects of bursting.

Cholinergic regulation of dendritic Ca2+ spikes controls firing mode of hippocampal CA3 pyramidal neurons

Active dendritic integrative mechanisms such as regenerative dendritic spikes enrich the information processing abilities of neurons and fundamentally contribute to behaviorally relevant computations. Dendritic Ca2+ spikes are generally thought to produce plateau-like dendritic depolarization and somatic complex spike burst (CSB) firing, which can initiate rapid changes in spatial coding properties of hippocampal pyramidal cells (PCs). However, here we reveal that a morpho-topographically distinguishable subpopulation of rat and mouse hippocampal CA3PCs exhibits compound apical dendritic Ca2+ spikes with unusually short duration that do not support the firing of sustained CSBs. These Ca2+ spikes are mediated by L-type Ca2+ channels and their time course is restricted by A- and M-type K+ channels. Cholinergic activation powerfully converts short Ca2+ spikes to long-duration forms, and facilitates and prolongs CSB firing. We propose that cholinergic neuromodulation controls the ability of a CA3PC subtype to generate sustained plateau potentials, providing a state-dependent dendritic mechanism for memory encoding and retrieval.

Neuronal sequences in population bursts encode information in human cortex.

Neural coding has traditionally been examined through changes in firing rates and latencies in response to different stimuli1-5. However, populations of neurons can also exhibit transient bursts of spiking activity, wherein neurons fire in a specific temporal order or sequence6-8. The human brain may utilize these neuronal sequences within population bursts to efficiently represent information9-12, thereby complementing the well-known neural code based on spike rate or latency. Here we examined this possibility by recording the spiking activity of populations of single units in the human anterior temporal lobe as eight participants performed a visual categorization task. We find that population spiking activity organizes into bursts during the task. The temporal order of spiking across the activated units within each burst varies across stimulus categories, creating unique stereotypical sequences for individual categories as well as for individual exemplars within a category. The information conveyed by the temporal order of spiking activity is separable from and complements the information conveyed by the units' spike rates or latencies following stimulus onset. Collectively, our data provide evidence that the human brain contains a complementary code based on the neuronal sequence within bursts of population spiking to represent information.

Stimulus-dependent spiking and bursting behavior in memsensor circuits: experiment and wave digital modeling

Biological information processing pathways in neuron assemblies rely on spike activity, encoding information in the time domain, and operating the highly parallel network at an outstanding robustness and efficiency. One particularly important aspect is the distributed, local pre-processing effectively converting stimulus-induced signals to action potentials, temporally encoding analog information. The field of brain-inspired electronics strives to adapt concepts of information processing in neural networks, e.g., stimulus detection and processing being intertwined. As such, stimulus-modulated resistive switching in memristive devices attracts an increasing attention. This work reports on a three-component memsensor circuit, featuring a UV-sensor, a memristive device with diffusive switching characteristics and a capacitor. Upon application of a DC bias, complex, stimulus-dependent spiking and brain-inspired bursting can be observed, as experimentally showcased using combination of a microstructured, tetrapodal ZnO sensor and a Au/SiOxNy/Ag cross-point memristive device. The experimental findings are corroborated by a wave digital model, which successfully replicates both types of behavior and outlines the relation of temporal variation of switching thresholds to the occurrence of bursting activity.Graphical abstract

Glial expression of Drosophila UBE3A causes spontaneous seizures that can be modulated by 5-HT signaling

Misexpression of the E3 ubiquitin ligase gene UBE3A is thought to contribute to a range of neurological disorders. In the context of Dup15q syndrome, additional genomic copies of UBE3A give rise to the autism, muscle hypotonia and spontaneous seizures characteristics of the disorder. In a Drosophila model of Dup 15q syndrome, it was recently shown that glial-driven expression of the UBE3A ortholog dube3a led to a “bang-sensitive” phenotype, where mechanical shock triggers convulsions, suggesting glial dube3a expression contributes to hyperexcitability in flies. Here we directly compare the consequences of glial- and neuronal-driven dube3a expression on motor coordination and seizure susceptibility in Drosophila.To quantify seizure-related behavioral events, we developed and trained a hidden Markov model that identified these events based on automated video tracking of fly locomotion. Both glial and neuronal driven dube3a expression led to clear motor phenotypes. However, only glial-driven dube3a expression displayed spontaneous seizure-associated immobilization events, that were clearly observed at high-temperature (38 °C). Using a tethered fly preparation amenable to electrophysiological monitoring of seizure activity, we found glial-driven dube3a flies display aberrant spontaneous spike discharges which are bilaterally synchronized. Neither neuronal-dube3a overexpressing flies, nor control flies displayed these firing patterns. We previously performed a drug screen for FDA approved compounds that can suppress bang-sensitivity in glial-driven dube3a expressing flies and identified certain 5-HT modulators as strong seizure suppressors. Here we found glial-driven dube3a flies fed the serotonin reuptake inhibitor vortioxetine and the 5-HT2A antagonist ketanserin displayed reduced immobilization and spike bursting, consistent with the previous study. Together these findings highlight the potential for glial pathophysiology to drive Dup15q syndrome-related seizure activity.

Emergent epileptiform activity in spinal sensory circuits drives ectopic bursting in afferent axons and sensory dysfunction after cord injury.

Spinal cord injury leads to hyperexcitability and dysfunction in spinal sensory processing. As hyperexcitable circuits can become epileptiform, we explored whether such activity emerges in a thoracic spinal cord injury (SCI) contusion model of neuropathic pain. Recordings from spinal sensory axons in multiple below-lesion segmental dorsal roots demonstrated that SCI facilitated the emergence of spontaneous ectopic burst spiking in afferent axons, which were correlated across multiple adjacent dorsal roots. Burst frequency correlated with behavioral mechanosensitivity. The same bursting events were recruited by afferent stimulation, and timing interactions with ongoing spontaneous bursts revealed that recruitment was limited by a prolonged post-burst refractory period. Ectopic bursting in afferent axons was driven by GABAA receptor activation, presumably by conversion of subthreshold GABAergic interneuronal presynaptic axoaxonic inhibitory actions to suprathreshold spiking. Collectively, the emergence of stereotyped bursting circuitry with hypersynchrony, sensory input activation, post-burst refractory period, and reorganization of connectivity represent defining features of an epileptiform network. Indeed, these same features were reproduced in naive animals with the convulsant 4-aminopyridine (fampridine). We conclude that spinal cord injury promotes the emergence of epileptiform activity in spinal sensory networks that promote profound corruption of sensory signaling. This includes hyperexcitability and bursting by ectopic spiking in afferent axons that propagate bidirectionally by reentrant central and peripheral projections as well as sensory circuit hypoexcitability during the burst refractory period. More broadly, the work links circuit hyperexcitability to epileptiform circuit emergence, further strengthening it as a conceptual basis to understand features of sensory dysfunction and neuropathic pain.

Neural coding of space by time.

The intertwining of space and time poses a significant scientific challenge, transcending disciplines from philosophy and physics to neuroscience. Deciphering neural coding, marked by its inherent spatial and temporal dimensions, has proven to be a complex task. In this paper, we present insights into temporal and spatial modes of neural coding and their intricate interplay, drawn from neuroscientific findings. We illustrate the conversion of a purely spatial input into the temporal form of a singular spike train, demonstrating storage, transmission to remote locations, and recall through spike bursts corresponding to Sharp Wave Ripples. Moreover, the converted temporal representation can be transformed back into a spatiotemporal pattern. The principles of the transformation process are illustrated using a simple feed-forward spiking neural network. The frequencies and phases of Subthreshold Membrane potential Oscillations play a pivotal role in this framework. The model offers insights into information multiplexing and phenomena such as stretching or compressing time of spike patterns.

Epilepsy as a Novel Phenotype of BPTF-Related Disorders

BackgroundNeurodevelopmental disorder with dysmorphic facies and distal limb anomalies (NEDDFL) is associated to BPTF gene haploinsufficiency. Epilepsy was not included in the initial descriptions of NEDDFL, but emerging evidence indicates that epileptic seizures occur in some affected individuals. This study aims to investigate the electroclinical epilepsy features in individuals with NEDDFL. MethodsWe enrolled individuals with BPTF-related seizures or interictal epileptiform discharges (IEDs) on electroencephalography (EEG). Demographic, clinical, genetic, raw EEG, and neuroimaging data as well as response to antiseizure medication were assessed. ResultsWe studied 11 individuals with a null variant in BPTF, including five previously unpublished ones. Median age at last observation was 9 years (range: 4 to 43 years). Eight individuals had epilepsy, one had a single unprovoked seizure, and two showed IEDs only. Key features included (1) early childhood epilepsy onset (median 4 years, range: 10 months to 7 years), (2) well-organized EEG background (all cases) and brief bursts of spikes and slow waves (50% of individuals), and (3) developmental delay preceding seizure onset. Spectrum of epilepsy severity varied from drug-resistant epilepsy (27%) to isolated IEDs without seizures (18%). Levetiracetam was widely used and reduced seizure frequency in 67% of the cases. ConclusionsOur study provides the first characterization of BPTF-related epilepsy. Early-childhood-onset epilepsy occurs in 19% of subjects, all presenting with a well-organized EEG background associated with generalized interictal epileptiform abnormalities in half of these cases. Drug resistance is rare.

Opposite effects of acute and chronic IGF1 on rat dorsal root ganglion neuron excitability.

Insulin-like growth factor-1 (IGF-1) is a polypeptide hormone with a ubiquitous distribution in numerous tissues and with various functions in both neuronal and non-neuronal cells. IGF-1 provides trophic support for many neurons of both the central and peripheral nervous systems. In the central nervous system (CNS), IGF-1R signaling regulates brain development, increases neuronal firing and modulates synaptic transmission. IGF-1 and IGF-IR are not only expressed in CNS neurons but also in sensory dorsal root ganglion (DRG) nociceptive neurons that convey pain signals. DRG nociceptive neurons express a variety of receptors and ion channels that are essential players of neuronal excitability, notably the ligand-gated cation channel TRPV1 and the voltage-gated M-type K+ channel, which, respectively, triggers and dampens sensory neuron excitability. Although many lines of evidence suggest that IGF-IR signaling contributes to pain sensitivity, its possible modulation of TRPV1 and M-type K+ channel remains largely unexplored. In this study, we examined the impact of IGF-1R signaling on DRG neuron excitability and its modulation of TRPV1 and M-type K+ channel activities in cultured rat DRG neurons. Acute application of IGF-1 to DRG neurons triggered hyper-excitability by inducing spontaneous firing or by increasing the frequency of spikes evoked by depolarizing current injection. These effects were prevented by the IGF-1R antagonist NVP-AEW541 and by the PI3Kinase blocker wortmannin. Surprisingly, acute exposure to IGF-1 profoundly inhibited both the TRPV1 current and the spike burst evoked by capsaicin. The Src kinase inhibitor PP2 potently depressed the capsaicin-evoked spike burst but did not alter the IGF-1 inhibition of the hyperexcitability triggered by capsaicin. Chronic IGF-1 treatment (24 h) reduced the spike firing evoked by depolarizing current injection and upregulated the M-current density. In contrast, chronic IGF-1 markedly increased the spike burst evoked by capsaicin. In all, our data suggest that IGF-1 exerts complex effects on DRG neuron excitability as revealed by its dual and opposite actions upon acute and chronic exposures.

Thalamocortical Dynamics during Rapid Eye Movement Sleep in the Mouse Somatosensory Pathway.

Rapid eye movement (REM) sleep, also referred to as paradoxical sleep for the striking resemblance of its electroencephalogram (EEG) to the one observed in wakefulness, is characterized by the occurrence of transient events such as limb twitches or facial and rapid eye movements. Here, we investigated the local activity of the primary somatosensory or barrel cortex (S1) in naturally sleeping head-fixed male mice during REM. Through local field potential recordings, we uncovered local appearances of spindle waves in the barrel cortex during REM concomitant with strong delta power, challenging the view of a wakefulness-like activity in REM. We further performed extra- and intracellular recordings of thalamic cells in head-fixed mice. Our data show high-frequency thalamic bursts of spikes and subthreshold spindle oscillations in approximately half of the neurons of the ventral posterior medial nucleus which further confirmed the thalamic origin of local cortical spindles in S1 in REM. Cortical spindle oscillations were suppressed, while thalamus spike firing increased, associated with rapid mouse whisker movements and S1 cortical activity transitioned to an activated state. During REM, the sensory thalamus and barrel cortex therefore alternate between high (wake-like) and low (non-REM sleep-like) activation states, potentially providing a neuronal substrate for mnemonic processes occurring during this paradoxical sleep stage.

Advanced iontronic spiking modes with multiscale diffusive dynamics in a fluidic circuit

Fluidic iontronics is emerging as a distinctive platform for implementing neuromorphic circuits, characterised by its reliance on the same aqueous medium and ionic signal carriers as the brain. Drawing upon recent theoretical advancements in both iontronic spiking circuits and in dynamic conductance of conical ion channels, which form fluidic memristors, we expand the repertoire of proposed neuronal spiking dynamics in iontronic circuits. Through a modelled circuit containing channels that carry a bipolar surface charge, we extract phasic bursting, mixed-mode spiking, tonic bursting, and threshold variability, all with spike voltages and frequencies within the typical range for mammalian neurons. These features are possible due to the strong dependence of the typical conductance memory retention time on the channel length, enabling timescales varying from individual spikes to bursts of multiple spikes within a single circuit. These advanced forms of neuronal-like spiking support the exploration of aqueous iontronics as an interesting platform for neuromorphic circuits.

Cell-type specific inhibitory plasticity in subicular pyramidal cells.

The balance between excitation and inhibition is essential to the proper function of cortical circuits. To maintain this balance during dynamic network activity, modulation of the strength of inhibitory synapses is a central requirement. In this study, we aimed to characterize perisomatic inhibition and its plasticity onto pyramidal cells (PCs) in the subiculum, the main output region of the hippocampus. We performed whole-cell patch-clamp recordings from the two main functional PC types, burst (BS) and regular spiking (RS) neurons in acute rat hippocampal slices and applied two different extracellular high-frequency stimulation paradigms: non-associative (presynaptic stimulation only) and associative stimulation (concurrent pre-and postsynaptic stimulation) to induce plasticity. Our results revealed cell type-specific differences in the expression of inhibitory plasticity depending on the induction paradigm: While associative stimulation caused robust inhibitory plasticity in both cell types, non-associative stimulation produced long-term potentiation in RS, but not in BS PCs. Analysis of paired-pulse ratio, variance of IPSPs, and postsynaptic Ca2+ buffering indicated a dominant postsynaptic calcium-dependent signaling and expression of inhibitory plasticity in both PC types. This divergence in inhibitory plasticity complements a stronger inhibition and a higher intrinsic excitability in RS as compared to BS neurons, suggesting differential involvement of the two PC types during network activation and information processing in the subiculum.

Magnetic Flux Sensor Based on Spiking Neurons with Josephson Junctions.

Josephson junctions (JJs) are superconductor-based devices used to build highly sensitive magnetic flux sensors called superconducting quantum interference devices (SQUIDs). These sensors may vary in design, being the radio frequency (RF) SQUID, direct current (DC) SQUID, and hybrid, such as D-SQUID. In addition, recently many of JJ's applications were found in spiking models of neurons exhibiting nearly biological behavior. In this study, we propose and investigate a new circuit model of a sensory neuron based on DC SQUID as part of the circuit. The dependence of the dynamics of the designed model on the external magnetic flux is demonstrated. The design of the circuit and derivation of the corresponding differential equations that describe the dynamics of the system are given. Numerical simulation is used for experimental evaluation. The experimental results confirm the applicability and good performance of the proposed magnetic-flux-sensitive neuron concept: the considered device can encode the magnetic flux in the form of neuronal dynamics with the linear section. Furthermore, some complex behavior was discovered in the model, namely the intermittent chaotic spiking and plateau bursting. The proposed design can be efficiently applied to developing the interfaces between circuitry and spiking neural networks. However, it should be noted that the proposed neuron design shares the main limitation of all the superconductor-based technologies, i.e., the need for a cryogenic and shielding system.

Two contrasting mediodorsal thalamic circuits target the mouse medial prefrontal cortex.

At the heart of the prefrontal network is the mediodorsal (MD) thalamus. Despite the importance of MD in a broad range of behaviors and neuropsychiatric disorders, little is known about the physiology of neurons in MD. We injected the retrograde tracer cholera toxin subunit B (CTB) into the medial prefrontal cortex (mPFC) of adult wild-type mice. We prepared acute brain slices and used current clamp electrophysiology to measure and compare the intrinsic properties of the neurons in MD that project to mPFC (MD→mPFC neurons). We show that MD→mPFC neurons are located predominantly in the medial (MD-M) and lateral (MD-L) subnuclei of MD. MD-L→mPFC neurons had shorter membrane time constants and lower membrane resistance than MD-M→mPFC neurons. Relatively increased hyperpolarization-activated cyclic nucleotide-gated (HCN) channel activity in MD-L neurons accounted for the difference in membrane resistance. MD-L neurons had a higher rheobase that resulted in less readily generated action potentials compared with MD-M→mPFC neurons. In both cell types, HCN channels supported generation of burst spiking. Increased HCN channel activity in MD-L neurons results in larger after-hyperpolarization potentials compared with MD-M neurons. These data demonstrate that the two populations of MD→mPFC neurons have divergent physiologies and support a differential role in thalamocortical information processing and potentially behavior.NEW & NOTEWORTHY To realize the potential of circuit-based therapies for psychiatric disorders that localize to the prefrontal network, we need to understand the properties of the populations of neurons that make up this network. The mediodorsal (MD) thalamus has garnered attention for its roles in executive functioning and social/emotional behaviors mediated, at least in part, by its projections to the medial prefrontal cortex (mPFC). Here, we identify and compare the physiology of the projection neurons in the two MD subnuclei that provide ascending inputs to mPFC in mice. Differences in intrinsic excitability between the two populations of neurons suggest that neuromodulation strategies targeting the prefrontal thalamocortical network will have differential effects on these two streams of thalamic input to mPFC.

SWCNTs/PEDOT:PSS nanocomposites-modified microelectrode arrays for revealing locking relations between burst and local field potential in cultured cortical networks

Burst and local field potential (LFP) are fundamental components of brain activity, representing fast and slow rhythms, respectively. Understanding the intricate relationship between burst and LFP is crucial for deciphering the underlying mechanisms of brain dynamics. In this study, we fabricated high-performance microelectrode arrays (MEAs) using the SWCNTs/PEDOT:PSS nanocomposites, which exhibited favorable electrical properties (low impedance: 12.8 ± 2.44 kΩ) and minimal phase delay (−11.96 ± 1.64°). These MEAs enabled precise exploration of the burst-LFP interaction in cultured cortical networks. After a 14-day period of culture, we used the MEAs to monitor electrophysiological activities and revealed a time-locking relationship between burst and LFP, indicating the maturation of the neural network. To further investigate this relationship, we modulated burst firing patterns by treating the neural culture with increasing concentrations of glycine. The results indicated that glycine effectively altered burst firing patterns, with both duration and spike count increasing as the concentration rose. This was accompanied by an enhanced level of time-locking between burst and LFP but a decrease in synchrony among neurons. This study not only highlighted the pivotal role of SWCNTs/PEDOT:PSS-modified MEAs in elucidating the interaction between burst and LFP, bridging the gap between slow and fast brain rhythms in vitro but also provides valuable insights into the potential therapeutic strategies targeting neurological disorders associated with abnormal rhythm generation.

Comparison of alterations in local field potentials and neuronal firing in mouse M1 and CA1 associated with central fatigue induced by high-intensity interval training and moderate-intensity continuous training.

The mechanisms underlying central fatigue (CF) induced by high-intensity interval training (HIIT) and moderate-intensity continuous training (MICT) are still not fully understood. In order to explore the effects of these exercises on the functioning of cortical and subcortical neural networks, this study investigated the effects of HIIT and MICT on local field potential (LFP) and neuronal firing in the mouse primary motor cortex (M1) and hippocampal CA1 areas. HIIT and MICT were performed on C57BL/6 mice, and simultaneous multichannel recordings were conducted in the M1 motor cortex and CA1 hippocampal region. A range of responses were elicited, including a decrease in coherence values of LFP rhythms in both areas, and an increase in slow and a decrease in fast power spectral density (PSD, n = 7-9) respectively. HIIT/MICT also decreased the gravity frequency (GF, n = 7-9) in M1 and CA1. Both exercises decreased overall firing rates, increased time lag of firing, declined burst firing rates and the number of spikes in burst, and reduced burst duration (BD) in M1 and CA1 (n = 7-9). While several neuronal firing properties showed a recovery tendency, the alterations of LFP parameters were more sustained during the 10-min post-HIIT/MICT period. MICT appeared to be more effective than HIIT in affecting LFP parameters, neuronal firing rate, and burst firing properties, particularly in CA1. Both exercises significantly affected neural network activities and local neuronal firing in M1 and CA1, with MICT associated with a more substantial and consistent suppression of functional integration between M1 and CA1. Our study provides valuable insights into the neural mechanisms involved in exercise-induced central fatigue by examining the changes in functional connectivity and coordination between the M1 and CA1 regions. These findings may assist individuals engaged in exercise in optimizing their exercise intensity and timing to enhance performance and prevent excessive fatigue. Additionally, the findings may have clinical implications for the development of interventions aimed at managing conditions related to exercise-induced fatigue.

Complex adaptive learning cortical neural network systems for solving time-fractional difference equations with bursting and mixed-mode oscillation behaviours

Complex networks have been programmed to mimic the input and output functions in multiple biophysical algorithms of cortical neurons at spiking resolution. Prior research has demonstrated that the ineffectual features of membranes can be taken into account by discrete fractional commensurate, non-commensurate and variable-order patterns, which may generate multiple kinds of memory-dependent behaviour. Firing structures involving regular resonator chattering, fast, chaotic spiking and chaotic bursts play important roles in cortical nerve cell insights and execution. Yet, it is unclear how extensively the behaviour of discrete fractional-order excited mechanisms can modify firing cell attributes. It is illustrated that the discrete fractional behaviour of the Izhikevich neuron framework can generate an assortment of resonances for cortical activity via the aforesaid scheme. We analyze the bifurcation using fragmenting periodic solutions to demonstrate the evolution of periods in the framework’s behaviour. We investigate various bursting trends both conceptually and computationally with the fractional difference equation. Additionally, the consequences of an excitable and inhibited Izhikevich neuron network (INN) utilizing a regulated factor set exhibit distinctive dynamic actions depending on fractional exponents regulating over extended exchanges. Ultimately, dynamic controllers for stabilizing and synchronizing the suggested framework are shown. This special spiking activity and other properties of the fractional-order model are caused by the memory trace that emerges from the fractional-order dynamics and integrates all the past activities of the neuron. Our results suggest that the complex dynamics of spiking and bursting can be the result of the long-term dependence and interaction of intracellular and extracellular ionic currents.

Neural cell engraftment therapy for sporadic Creutzfeldt-Jakob disease restores neuroelectrophysiological parameters in a cerebral organoid model

BackgroundSporadic Creutzfeldt-Jakob disease (sCJD), the most common human prion disease, is a fatal neurodegenerative disease with currently no treatment options. Stem cell therapy for neurodegenerative diseases is emerging as a possible treatment option. However, while there are a few clinical trials for other neurodegenerative disorders such as Parkinson’s disease, prion disease cell therapy research has so far been confined to animal models.MethodsHere, we use a novel approach to study cell therapies in sCJD using a human cerebral organoid model. Cerebral organoids can be infected with sCJD prions allowing us to assess how neural precursor cell (NPC) therapy impacts the progression of sCJD. After 90 days of sCJD or mock infection, organoids were either seeded with NPCs or left unseeded and monitored for cellular composition changes, prion infection parameters and neuroelectrophysiological function at 180 days post-infection.ResultsOur results showed NPCs integrated into organoids leading to an increase in neuronal markers and changes in cell signaling irrespective of sCJD infection. Although a small, but significant, decrease in protease-resistant PrP deposition was observed in the CJD-infected organoids that received the NPCs, other disease-associated parameters showed minimal changes. However, the NPCs had a beneficial impact on organoid function following infection. sCJD infection caused reduction in neuronal spike rate and mean burst spike rate, indicative of reduced action potentials. NPC seeding restored these electrophysiological parameters to the uninfected control level.ConclusionsTogether with the previous animal studies, our results support that cell therapy may have some functional benefit for the treatment of human prion diseases.

Rescue of sharp wave-ripples and prevention of network hyperexcitability in the ventral but not the dorsal hippocampus of a rat model of fragile X syndrome.

Fragile X syndrome (FXS) is a genetic neurodevelopmental disorder characterized by intellectual disability and is related to autism. FXS is caused by mutations of the fragile X messenger ribonucleoprotein 1 gene (Fmr1) and is associated with alterations in neuronal network excitability in several brain areas including hippocampus. The loss of fragile X protein affects brain oscillations, however, the effects of FXS on hippocampal sharp wave-ripples (SWRs), an endogenous hippocampal pattern contributing to memory consolidation have not been sufficiently clarified. In addition, it is still not known whether dorsal and ventral hippocampus are similarly affected by FXS. We used a Fmr1 knock-out (KO) rat model of FXS and electrophysiological recordings from the CA1 area of adult rat hippocampal slices to assess spontaneous and evoked neural activity. We find that SWRs and associated multiunit activity are affected in the dorsal but not the ventral KO hippocampus, while complex spike bursts remain normal in both segments of the KO hippocampus. Local network excitability increases in the dorsal KO hippocampus. Furthermore, specifically in the ventral hippocampus of KO rats we found an increased effectiveness of inhibition in suppressing excitation and an upregulation of α1GABAA receptor subtype. These changes in the ventral KO hippocampus are accompanied by a striking reduction in its susceptibility to induced epileptiform activity. We propose that the neuronal network specifically in the ventral segment of the hippocampus is reorganized in adult Fmr1-KO rats by means of balanced changes between excitability and inhibition to ensure normal generation of SWRs and preventing at the same time derailment of the neural activity toward hyperexcitability.

Bursting dynamics in a spiking neuron with a memristive voltage-gated channel

We introduce a voltage-gated conductance model for an artificial neuron that exhibits tonic, fast, and two types of intrinsic burst spiking. The spike generation is achieved with a single voltage-gated channel that exploits the conductance commutation properties of a two-terminal memristive device. Our circuit implementation is of unprecedented simplicity, using just four electronic components, all conventional, cheap and out-of-the-shelf. Our bursting neuron is a two-compartment model, similar to the Pinsky–Rinzel model. We obtain the full phase diagram and discuss the origin of the different regions. We find that the spike traces of the model bare striking similarity to experimental biological neuronal recordings. Our work may open a new way to investigate neural pathologies, such as epilepsy and Parkinson’s disease, from the study of the phase diagram and the transitions between spiking states of physical neuron models.