Modelling Artificial Stimulation and Response in Peripheral Nerves Including Ephaptic Interactions

This research aims to (1) extend our knowledge on the response of peripheral nerves to artificial stimulation for sensory feedback provision from neural interfaces, and (2) create a computational tool to facilitate this study. We were interested in studying how ephaptic coupling between myelinated fibers influences activity in nerve trunks under artificial stimulation and during action potential propagation. Ephaptic interaction simulations in nerve trunks were performed to quantify this influence. For this, we created peripheral nerve models containing electrodes for electrical stimulation and recording within a tool that can be further used in electrode design optimisation and neural activity research. The created model can use a self-contained or a hybrid field-neuron method. The self-contained method uses a resistor network that electrically couples all axons, tissues, electrodes, and surrounding medium, and is solved by the NEURON simulation environment. The resistor network uses weighted Voronoi tessellations in the Laguerre geometry to define the electrical connections between all nerve elements given any cross-sectional anatomy. The hybrid field-neuron approach also uses the resistor network to compute the fields, but uses them stimulate fiber in a separate simulation. The self-contained model was designed so that it could simulate artificial stimulation, neural activity with ephaptic coupling and electrode recordings simultaneously. Researchers often assume ephaptic coupling is weak among myelinated axons, and therefore, tend to ignore it. Simulations carried out in this work, however, show that ephaptic coupling increases axon recruitment during artificial stimulation. This effect should be taken into account in further research. On the other hand, ephaptic coupling during propagation in realistic bundles with large numbers of heterogeneous myelinated fibers is weaker, unstable, and more complex than what is known from previous studies on bundles of few homogeneous fibers. This research provides detailed results and insights on these aspects of peripheral neural activity

Stochastic Simulations on the Reliability of Action Potential Propagation in Thin Axons

It is generally assumed that axons use action potentials (APs) to transmit information fast and reliably to synapses. Yet, the reliability of transmission along fibers below 0.5 μm diameter, such as cortical and cerebellar axons, is unknown. Using detailed models of rodent cortical and squid axons and stochastic simulations, we show how conduction along such thin axons is affected by the probabilistic nature of voltage-gated ion channels (channel noise). We identify four distinct effects that corrupt propagating spike trains in thin axons: spikes were added, deleted, jittered, or split into groups depending upon the temporal pattern of spikes. Additional APs may appear spontaneously; however, APs in general seldom fail (<1%). Spike timing is jittered on the order of milliseconds over distances of millimeters, as conduction velocity fluctuates in two ways. First, variability in the number of Na channels opening in the early rising phase of the AP cause propagation speed to fluctuate gradually. Second, a novel mode of AP propagation (stochastic microsaltatory conduction), where the AP leaps ahead toward spontaneously formed clusters of open Na channels, produces random discrete jumps in spike time reliability. The combined effect of these two mechanisms depends on the pattern of spikes. Our results show that axonal variability is a general problem and should be taken into account when considering both neural coding and the reliability of synaptic transmission in densely connected cortical networks, where small synapses are typically innervated by thin axons. In contrast we find that thicker axons above 0.5 μm diameter are reliable

Complex chemical dynamics through engineering-like methods

Most of the problems in modern structural design can be described with a set of equation; solutions of these mathematical models can lead the engineer and designer to get info during the design stage. The same holds true for physical-chemistry; this branch of chemistry uses mathematics and physics in order to explain real chemical phenomena. In this work two extremely different chemical processes will be studied; the dynamic of an artificial molecular motor and the generation and propagation of the nervous signals between excitable cells and tissues like neurons and axons. These two processes, in spite of their chemical and physical differences, can be both described successfully by partial differential equations, that are, respectively the Fokker-Planck equation and the Hodgkin and Huxley model. With the aid of an advanced engineering software these two processes have been modeled and simulated in order to extract a lot of physical informations about them and to predict a lot of properties that can be, in future, extremely useful during the design stage of both molecular motors and devices which rely their actions on the nervous communications between active fibres

Anatomy and physiology of the thick-tufted layer 5 pyramidal neuron

The thick-tufted layer 5 (TTL5) pyramidal neuron is one of the most extensively studied neuron types in the mammalian neocortex and has become a benchmark for understanding information processing in excitatory neurons. By virtue of having the widest local axonal and dendritic arborization, the TTL5 neuron encompasses various local neocortical neurons and thereby defines the dimensions of neocortical microcircuitry. The TTL5 neuron integrates input across all neocortical layers and is the principal output pathway funneling information flow to subcortical structures. Several studies over the past decades have investigated the anatomy, physiology, synaptology, and pathophysiology of the TTL5 neuron. This review summarizes key discoveries and identifies potential avenues of research to facilitate an integrated and unifying understanding on the role of a central neuron in the neocortex

Synaptic depression and its relation to behavioral habituation within anterior piriform cortex.

The onset, time course, and extent of LOT synaptic depression during both in vitro electrical and in vivo odorant stimulation methods were similar. Similar to the odor specificity of cortical odor adaptation in vivo, there was no evidence of heterosynaptic depression between independent inputs in vitro. In vitro evidence suggests at least two mechanisms contribute to this activity-dependent synaptic depression: a rapidly recovering presynaptic depression during the initial 10--20 sec of the post-train recovery period and a longer lasting (120 sec) depression that can be blocked by the metabotropic glutamate receptor (mGluR) II/III antagonist (RS)-alpha-cyclopropyl-4-phosphonophenylglycine (CPPG) and by the beta-adrenergic receptor agonist isoproterenol. Importantly, in line with the in vitro findings, both adaptation of odor responses in the 15--35 Hz spectral range and the associated synaptic depression can also be blocked by intracortical infusion of CPPG in vivo. Additionally, blockade of group II/III mGluR activation in aPCX prevents habituation of the odor-evoked heart rate orienting response behavior in awake behaving rats.Short-term behavioral habituation is the response decrement observed in many behaviors that occurs during repeated presentation of non-reinforced stimuli. Within a number of invertebrate models of short-term behavioral habituation, depression of a defined synapse has been implicated as the mechanism. However, the synaptic mechanisms of short-term behavioral habituation have not been identified within mammals.Anterior piriform cortex (aPCX) neurons rapidly filter repetitive odor stimuli despite relatively maintained input from mitral/tufted cells. This cortical adaptation is correlated with short-term depression of afferent synapses, in vivo. The purpose of this study was to elucidate mechanisms underlying this non-associative neural plasticity using in vivo and in vitro preparations, determine its role in cortical odor adaptation and ultimately look at its relation to behavioral odor habituation. Lateral olfactory tract (LOT)-evoked responses were recorded in rat aPCX coronal slices. Extracellular and intracellular potentials were recorded before and after simulated odor stimulation of the LOT. Results were compared with in vivo intracellular recordings from aPCX layer II/III neurons and field recordings in urethane-anesthetized rats stimulated with odorants