Impact of Dendritic Size and Dendritic Topology on Burst Firing in Pyramidal Cells

Neurons display a wide range of intrinsic firing patterns. A particularly relevant pattern for neuronal signaling and synaptic plasticity is burst firing, the generation of clusters of action potentials with short interspike intervals. Besides ion-channel composition, dendritic morphology appears to be an important factor modulating firing pattern. However, the underlying mechanisms are poorly understood, and the impact of morphology on burst firing remains insufficiently known. Dendritic morphology is not fixed but can undergo significant changes in many pathological conditions. Using computational models of neocortical pyramidal cells, we here show that not only the total length of the apical dendrite but also the topological structure of its branching pattern markedly influences inter- and intraburst spike intervals and even determines whether or not a cell exhibits burst firing. We found that there is only a range of dendritic sizes that supports burst firing, and that this range is modulated by dendritic topology. Either reducing or enlarging the dendritic tree, or merely modifying its topological structure without changing total dendritic length, can transform a cell's firing pattern from bursting to tonic firing. Interestingly, the results are largely independent of whether the cells are stimulated by current injection at the soma or by synapses distributed over the dendritic tree. By means of a novel measure called mean electrotonic path length, we show that the influence of dendritic morphology on burst firing is attributable to the effect both dendritic size and dendritic topology have, not on somatic input conductance, but on the average spatial extent of the dendritic tree and the spatiotemporal dynamics of the dendritic membrane potential. Our results suggest that alterations in size or topology of pyramidal cell morphology, such as observed in Alzheimer's disease, mental retardation, epilepsy, and chronic stress, could change neuronal burst firing and thus ultimately affect information processing and cognition

Simulation and experimental study of proton bunch self-modulation in plasma with linear density gradients

We present numerical simulations and experimental results of the self-modulation of a long proton bunch in a plasma with linear density gradients along the beam path. Simulation results agree with the experimental results reported [F. Braunmller, T. Nechaeva et al. (AWAKE Collaboration), Phys. Rev. Lett. 125, 264801 (2020)PRLTAO0031-900710.1103/PhysRevLett.125.264801]: with negative gradients, the charge of the modulated bunch is lower than with positive gradients. In addition, the bunch modulation frequency varies with gradient. Simulation results show that dephasing of the wakefields with respect to the relativistic protons along the plasma is the main cause for the loss of charge. The study of the modulation frequency reveals details about the evolution of the self-modulation process along the plasma. In particular for negative gradients, the modulation frequency across time-resolved images of the bunch indicates the position along the plasma where protons leave the wakefields. Simulations and experimental results are in excellent agreement

Experimental study of extended timescale dynamics of a plasma wakefield driven by a self-modulated proton bunch

Plasma wakefield dynamics over timescales up to 800 ps, approximately 100 plasma periods, are studied experimentally at the Advanced Wakefield Experiment (AWAKE). The development of the longitudinal wakefield amplitude driven by a self-modulated proton bunch is measured using the external injection of witness electrons that sample the fields. In simulation, resonant excitation of the wakefield causes plasma electron trajectory crossing, resulting in the development of a potential outside the plasma boundary as electrons are transversely ejected. Trends consistent with the presence of this potential are experimentally measured and their dependence on wakefield amplitude are studied via seed laser timing scans and electron injection delay scan

Experimental Observation of Proton Bunch Modulation in a Plasma at Varying Plasma Densities

We give direct experimental evidence for the observation of the full transverse self-modulation of a long, relativistic proton bunch propagating through a dense plasma. The bunch exits the plasma with a periodic density modulation resulting from radial wakefield effects. We show that the modulation is seeded by a relativistic ionization front created using an intense laser pulse copropagating with the proton bunch. The modulation extends over the length of the proton bunch following the seed point. By varying the plasma density over one order of magnitude, we show that the modulation frequency scales with the expected dependence on the plasma density, i.e., it is equal to the plasma frequency, as expected from theory

Transition between Instability and Seeded Self-Modulation of a Relativistic Particle Bunch in Plasma

We use a relativistic ionization front to provide various initial transverse wakefield amplitudes for the self-modulation of a long proton bunch in plasma. We show experimentally that, with sufticient initial amplitude [>= (4.1 +/- 0.4) MV/m], the phase of the modulation along the bunch is reproducible from event to event, with 3%-7% (of 2 pi) rms variations all along the bunch. The phase is not reproducible for lower initial amplitudes. We observe the transition between these two regimes. Phase reproducibility is essential for deterministic external injection of particles to be accelerated

Experimental study of wakefields driven by a self-modulating proton bunch in plasma

We study experimentally the longitudinal and transverse wakefields driven by a highly relativistic proton bunch during self-modulation in plasma. We show that the wakefields' growth and amplitude increase with increasing seed amplitude as well as with the proton bunch charge in the plasma. We study transverse wakefields using the maximum radius of the proton bunch distribution measured on a screen downstream from the plasma. We study longitudinal wakefields by externally injecting electrons and measuring their final energy. Measurements agree with trends predicted by theory and numerical simulations and validate our understanding of the development of self-modulation. Experiments were performed in the context of the Advanced Wakefield Experiment (AWAKE)

Proton Bunch Self-Modulation in Plasma with Density Gradient

We study experimentally the effect of linear plasma density gradients on the self-modulation of a 400 GeV proton bunch. Results show that a positive or negative gradient increases or decreases the number of microbunches and the relative charge per microbunch observed after 10 m of plasma. The measured modulation frequency also increases or decreases. With the largest positive gradient we observe two frequencies in the modulation power spectrum. Results are consistent with changes in wakefields' phase velocity due to plasma density gradients adding to the slow wakefields' phase velocity during self-modulation growth predicted by linear theory

Consensus statement on abusive head trauma in infants and young children

Abusive head trauma (AHT) is the leading cause of fatal head injuries in children younger than 2 years. A multidisciplinary team bases this diagnosis on history, physical examination, imaging and laboratory findings. Because the etiology of the injury is multifactorial (shaking, shaking and impact, impact, etc.) the current best and inclusive term is AHT. There is no controversy concerning the medical validity of the existence of AHT, with multiple components including subdural hematoma, intracranial and spinal changes, complex retinal hemorrhages, and rib and other fractures that are inconsistent with the provided mechanism of trauma. The workup must exclude medical diseases that can mimic AHT. However, the courtroom has become a forum for speculative theories that cannot be reconciled with generally accepted medical literature. There is no reliable medical evidence that the following processes are causative in the constellation of injuries of AHT: cerebral sinovenous thrombosis, hypoxic-ischemic injury, lumbar puncture or dysphagic choking/vomiting. There is no substantiation, at a time remote from birth, that an asymptomatic birth-related subdural hemorrhage can result in rebleeding and sudden collapse. Further, a diagnosis of AHT is a medical conclusion, not a legal determination of the intent of the perpetrator or a diagnosis of murder. We hope that this consensus document reduces confusion by recommending to judges and jurors the tools necessary to distinguish genuine evidence-based opinions of the relevant medical community from legal arguments or etiological speculations that are unwarranted by the clinical findings, medical evidence and evidence-based literature