Self-repair ability of evolved self-assembling systems in cellular automata

Self-repairing systems are those that are able to reconfigure themselves following disruptions to bring them back into a defined normal state. In this paper we explore the self-repair ability of some cellular automata-like systems, which differ from classical cellular automata by the introduction of a local diffusion process inspired by chemical signalling processes in biological development. The update rules in these systems are evolved using genetic programming to self-assemble towards a target pattern. In particular, we demonstrate that once the update rules have been evolved for self-assembly, many of those update rules also provide a self-repair ability without any additional evolutionary process aimed specifically at self-repair

Development of GABAergic and glycinergic transmission in the neonatal rat dorsal horn

Cutaneous spinal sensory transmission appears to lack inhibitory control in the newborn spinal cord, but the properties of GABAergic and glycinergic synapses in the neonatal dorsal horn have not been characterized. Whole-cell patch-clamp recordings from rat superficial dorsal horn neurons in spinal cord slices at postnatal day 0 (P0) to P2, P6 - P7, and P13 - P14 revealed an age-dependent increase in the frequency of spontaneous IPSCs, which were abolished by the GABA(A) receptor (GABA(A)R) antagonist bicuculline between P0 and P7 but not at P14. GABA(A)R-mediated miniature IPSCs (mIPSCs), but not glycinergic mIPSCs, were present at birth, and GABA mIPSCs remained more frequent than glycine mIPSCs at all ages. Sciatic nerve stimulation resulted in IPSCs with both GABAergic and glycinergic components, although a larger contribution arose from GABAA receptors at all ages. In gramicidin perforated patch-clamp recordings, exogenous GABA applications produced depolarization in 40% of neurons at P0 - P2, but the reversal potential of GABA-evoked currents (E-GABA) was consistently more negative than action potential threshold at this age. By P6 - P7, GABA evoked only membrane hyperpolarization. The GABA(B)R agonist baclofen elicited an outward current in all neurons with peak amplitudes observed by P6 - P7 and abolished sciatic nerve-evoked monosynaptic glutamatergic EPSCs in all groups. The results show considerable postnatal development of inhibitory processing in the dorsal horn with GABAergic mechanisms initially dominant over glycinergic events. GABA(A)R-mediated depolarizations during the first postnatal week are likely to be important for the maturation of spinal networks but do not provide a major excitatory drive to the newborn dorsal horn

"Going back to our roots": second generation biocomputing

Researchers in the field of biocomputing have, for many years, successfully "harvested and exploited" the natural world for inspiration in developing systems that are robust, adaptable and capable of generating novel and even "creative" solutions to human-defined problems. However, in this position paper we argue that the time has now come for a reassessment of how we exploit biology to generate new computational systems. Previous solutions (the "first generation" of biocomputing techniques), whilst reasonably effective, are crude analogues of actual biological systems. We believe that a new, inherently inter-disciplinary approach is needed for the development of the emerging "second generation" of bio-inspired methods. This new modus operandi will require much closer interaction between the engineering and life sciences communities, as well as a bidirectional flow of concepts, applications and expertise. We support our argument by examining, in this new light, three existing areas of biocomputing (genetic programming, artificial immune systems and evolvable hardware), as well as an emerging area (natural genetic engineering) which may provide useful pointers as to the way forward.Comment: Submitted to the International Journal of Unconventional Computin

GABA_{B} Receptors Regulate Chick Retinal Calcium Waves

Correlated spiking activity and associated Ca²⁺ waves in the developing retina are important in determining the connectivity of the visual system. Here, we show that GABA, via GABA_{B} receptors, regulates the temporal characteristics of Ca²⁺ waves occurring before synapse formation in the embryonic chick retina. Blocking ionotropic GABA receptors did no affect these Ca²⁺ transients. However, when these receptors were blocked, GABA abolished the transients, as did the GABA_{B} agonist baclofen. The action of baclofen was prevented by the GABA_{B} antagonistp-3-aminopropyl-p-diethoxymethyl phosphoric acid (CGP35348). CGP35348 alone increased the duration of the transients, showing that GABA_{B} receptors are tonically activated by endogenous GABA. Blocking the GABA transporter GAT-1 with 1-(4,4-diphenyl-3-butenyl)-3-piperidine carboxylic acid (SKF89976A) reduced the frequency of the transients. This reduction was prevented by CGP35348 and thus resulted from activation of GABA_{B} receptors by an increase in external [GABA]. The effect of GABA_{B} receptor activation persisted in the presence of activators and blockers of the cAMP–PKA pathway. Immunocytochemistry showed GABA_{B} receptors and GAT-1 transporters on ganglion and amacrine cells from the earliest times when Ca²⁺ waves occur (embryonic day 8). Patch-clamp recordings showed that K⁺ channels on ganglion cell layer neurons are not modulated by GABA_{B} receptors, whereas Ca²⁺ channels are; however, Ca²⁺ channel blockade with ω-conotoxin-GVIA or nimodipine did not prevent Ca²⁺ waves. Thus, the regulation of Ca²⁺ waves by GABA_{B} receptors occurs independently of N- and L-type Ca²⁺ channels and does not involve K⁺ channels of the ganglion cell layer. GABA_{B} receptors are likely to be of key importance in regulating retinal development

Non-hyperpolarizing GABA B receptor activation regulates neuronal migration and neurite growth and specification by cAMP/LKB1

γ-Aminobutyric acid is the principal inhibitory neurotransmitter in adults, acting through ionotropic chloride-permeable GABAA receptors (GABAARs), and metabotropic GABABRs coupled to calcium or potassium channels, and cyclic AMP signalling. During early development, γ-aminobutyric acid is the main neurotransmitter and is not hyperpolarizing, as GABAAR activation is depolarizing while GABABRs lack coupling to potassium channels. Despite extensive knowledge on GABAARs as key factors in neuronal development, the role of GABABRs remains unclear. Here we address GABABR function during rat cortical development by in utero knockdown (short interfering RNA) of GABABR in pyramidal-neuron progenitors. GABABR short interfering RNA impairs neuronal migration and axon/dendrite morphological maturation by disrupting cyclic AMP signalling. Furthermore, GABABR activation reduces cyclic AMP-dependent phosphorylation of LKB1, a kinase involved in neuronal polarization, and rescues LKB1 overexpression-induced defects in cortical development. Thus, non-hyperpolarizing activation of GABABRs during development promotes neuronal migration and morphological maturation by cyclic AMP/LKB1 signalling