Action potential energy efficiency varies among neuron types in vertebrates and invertebrates.

The initiation and propagation of action potentials (APs) places high demands on the energetic resources of neural tissue. Each AP forces ATP-driven ion pumps to work harder to restore the ionic concentration gradients, thus consuming more energy. Here, we ask whether the ionic currents underlying the AP can be predicted theoretically from the principle of minimum energy consumption. A long-held supposition that APs are energetically wasteful, based on theoretical analysis of the squid giant axon AP, has recently been overturned by studies that measured the currents contributing to the AP in several mammalian neurons. In the single compartment models studied here, AP energy consumption varies greatly among vertebrate and invertebrate neurons, with several mammalian neuron models using close to the capacitive minimum of energy needed. Strikingly, energy consumption can increase by more than ten-fold simply by changing the overlap of the Na+ and K+ currents during the AP without changing the APs shape. As a consequence, the height and width of the AP are poor predictors of energy consumption. In the Hodgkin–Huxley model of the squid axon, optimizing the kinetics or number of Na+ and K+ channels can whittle down the number of ATP molecules needed for each AP by a factor of four. In contrast to the squid AP, the temporal profile of the currents underlying APs of some mammalian neurons are nearly perfectly matched to the optimized properties of ionic conductances so as to minimize the ATP cost

Models wagging the dog: are circuits constructed with disparate parameters?

In a recent article, Prinz, Bucher, and Marder (2004) addressed the fundamental question of whether neural systems are built with a fixed blueprint of tightly controlled parameters or in a way in which properties can vary largely from one individual to another, using a database modeling approach. Here, we examine the main conclusion that neural circuits indeed are built with largely varying parameters in the light of our own experimental and modeling observations. We critically discuss the experimental and theoretical evidence, including the general adequacy of database approaches for questions of this kind, and come to the conclusion that the last word for this fundamental question has not yet been spoken

How feedback inhibition shapes spike-timing-dependent plasticity and its implications for recent Schizophrenia models

It has been shown that plasticity is not a fixed property but, in fact, changes depending on the location of the synapse on the neuron and/or changes of biophysical parameters. Here we investigate how plasticity is shaped by feedback inhibition in a cortical microcircuit. We use a differential Hebbian learning rule to model spike-timing dependent plasticity and show analytically that the feedback inhibition shortens the time window for LTD during spike-timing dependent plasticity but not for LTP. We then use a realistic GENESIS model to test two hypothesis about interneuron hypofunction and conclude that a reduction in GAD67 is the most likely candidate as the cause for hypofrontality as observed in Schizophrenia

Probing the dynamics of identified neurons with a data-driven modeling approach

In controlling animal behavior the nervous system has to perform within the operational limits set by the requirements of each specific behavior. The implications for the corresponding range of suitable network, single neuron, and ion channel properties have remained elusive. In this article we approach the question of how well-constrained properties of neuronal systems may be on the neuronal level. We used large data sets of the activity of isolated invertebrate identified cells and built an accurate conductance-based model for this cell type using customized automated parameter estimation techniques. By direct inspection of the data we found that the variability of the neurons is larger when they are isolated from the circuit than when in the intact system. Furthermore, the responses of the neurons to perturbations appear to be more consistent than their autonomous behavior under stationary conditions. In the developed model, the constraints on different parameters that enforce appropriate model dynamics vary widely from some very tightly controlled parameters to others that are almost arbitrary. The model also allows predictions for the effect of blocking selected ionic currents and to prove that the origin of irregular dynamics in the neuron model is proper chaoticity and that this chaoticity is typical in an appropriate sense. Our results indicate that data driven models are useful tools for the in-depth analysis of neuronal dynamics. The better consistency of responses to perturbations, in the real neurons as well as in the model, suggests a paradigm shift away from measuring autonomous dynamics alone towards protocols of controlled perturbations. Our predictions for the impact of channel blockers on the neuronal dynamics and the proof of chaoticity underscore the wide scope of our approach

Excitable Media Seminar

The simulation data presented here, and the conceptual framework developed for their interpretation are, both, in need of substantial refinement and extension. However, granting that they are initial pointers of some merit, and elementary indicators of general principles, several implications follow: the activity patterns of neurons and their assemblies are\ud interdependent with the extracellular milieu in which they are embedded, and to whose time varying composition they contribute. The complexity of this interdependence in the temporal dimension forecloses any time and context invariant relation between what the experimenter may consider stimulus input and its representation in neural activity. Hence, ideas of coding by (quasi)-digital neurons are called in question by the mutual interdependence of neurons and their\ud humoral milieu. Instead, concepts of 'mass action' in the Nervous system gain a new perspective: this time augmented by including the chemical medium surrounding neurons as part of the dynamics of the system as a whole. Accordingly, a meaningful way to describe activity in a neuron assembly would be in terms of a state space in which it can move along an infinite number of trajectories.\u

An On-chip Trainable and Clock-less Spiking Neural Network with 1R Memristive Synapses

Spiking neural networks (SNNs) are being explored in an attempt to mimic brain's capability to learn and recognize at low power. Crossbar architecture with highly scalable Resistive RAM or RRAM array serving as synaptic weights and neuronal drivers in the periphery is an attractive option for SNN. Recognition (akin to reading the synaptic weight) requires small amplitude bias applied across the RRAM to minimize conductance change. Learning (akin to writing or updating the synaptic weight) requires large amplitude bias pulses to produce a conductance change. The contradictory bias amplitude requirement to perform reading and writing simultaneously and asynchronously, akin to biology, is a major challenge. Solutions suggested in the literature rely on time-division-multiplexing of read and write operations based on clocks, or approximations ignoring the reading when coincidental with writing. In this work, we overcome this challenge and present a clock-less approach wherein reading and writing are performed in different frequency domains. This enables learning and recognition simultaneously on an SNN. We validate our scheme in SPICE circuit simulator by translating a two-layered feed-forward Iris classifying SNN to demonstrate software-equivalent performance. The system performance is not adversely affected by a voltage dependence of conductance in realistic RRAMs, despite departing from linearity. Overall, our approach enables direct implementation of biological SNN algorithms in hardware