Ion-Channel Noise Places Limits on the Miniaturization of the Brain’s Wiring

Abstract

The action potential (AP) is transmitted by the concerted action of voltage-gated ion channels. Thermodynamic fluctuations in channel proteins produce probabilistic gating behavior, causing channel noise. Miniaturizing signaling systems increases susceptibility to noise, and with many cortical, cerebellar, and peripheral axons <0.5 mum diameter [1, 2 and 3], channel noise could be significant [4 and 5]. Using biophysical theory and stochastic simulations, we investigated channel-noise limits in unmyelinated axons. Axons of diameter below 0.1 microm become inoperable because single, spontaneously opening Na channels generate spontaneous AP at rates that disrupt communication. This limiting diameter is relatively insensitive to variations in biophysical parameters (e.g., channel properties and density, membrane conductance and leak) and will apply to most spiking axons. We demonstrate that the essential molecular machinery can, in theory, fit into 0.06 microm diameter axons. However, a comprehensive survey of anatomical data shows a lower limit for AP-conducting axons of 0.08-0.1 microm diameter. Thus, molecular fluctuations constrain the wiring density of brains. Fluctuations have implications for epilepsy and neuropathic pain because changes in channel kinetics or axonal properties can change the rate at which channel noise generates spontaneous activity.

Neuronal energy consumption: biophysics, efficiency and evolution

“…This extends from the size and structure of single neurons [12,42,43,61] and neural tracts [62,63], to the placement of neurons within neural networks or regions within the cortex [e.g. [64][65][66][67][68].…”

“…Size is a key factor in determining neuronal energy consumption and the energy efficiency of information processing. Small neurons have lower total membrane capacitance but also less membrane area in which to house ion channels and receptors, and less volume in which to accommodate mitochondria [12,42,[61][62][63]. So, small neurons will be limited in terms of bandwidth and will be noisy but they will have low energy consumption [12,42].…”

“…Within axonal tracts, the distribution of diameters tends to be skewed towards thin axons [62,63]. Thinner axons also tend to have lower firing frequencies than thicker axons.…”

Comparison of Langevin and Markov channel noise models for neuronal signal generation

“…The information coded was quantified in single compartment models that support action potentials (spiking models) as well as those supporting only analogue signals (non-spiking models) because both types of neurons are found in vertebrate and invertebrate nervous systems [22]. We varied the size of the single compartment being simulated to determine whether differences between the exact and approximate methods are greater in smaller compartments with fewer voltage-gated ion channels where the effects of channel noise are more pronounced [12,23]. We also compared the performance of the exact and approximate methods in the presence or absence of extrinsic noise.…”

Are smaller animals behaviourally limited? Lack of clear constraints in miniature spiders

“…The surface area of a neuron is positively related to its energy consumption (Niven et al 2007), and smaller neurons have proportionally larger surface areas, so comparable informationprocessing capabilities in a smaller brain will result in increased costs due to higher density of metabolic activity (Niven et al 2007;Chittka & Niven 2009). Furthermore, there may also be lower limits on the sizes of functional axons, due to spontaneous opening of voltage-gated ion channels (Faisal et al 2005). Additionally, there may be a lower limit to neuron size imposed by the nucleus, as the percentage of the cell occupied by the nucleus is larger in smaller cells (Polilov & Beutel 2009).…”