Control of Ca2+ Influx and Calmodulin Activation by SK-Channels in Dendritic Spines.

The key trigger for Hebbian synaptic plasticity is influx of Ca2+ into postsynaptic dendritic spines. The magnitude of [Ca2+] increase caused by NMDA-receptor (NMDAR) and voltage-gated Ca2+ -channel (VGCC) activation is thought to determine both the amplitude and direction of synaptic plasticity by differential activation of Ca2+ -sensitive enzymes such as calmodulin. Ca2+ influx is negatively regulated by Ca2+ -activated K+ channels (SK-channels) which are in turn inhibited by neuromodulators such as acetylcholine. However, the precise mechanisms by which SK-channels control the induction of synaptic plasticity remain unclear. Using a 3-dimensional model of Ca2+ and calmodulin dynamics within an idealised, but biophysically-plausible, dendritic spine, we show that SK-channels regulate calmodulin activation specifically during neuron-firing patterns associated with induction of spike timing-dependent plasticity. SK-channel activation and the subsequent reduction in Ca2+ influx through NMDARs and L-type VGCCs results in an order of magnitude decrease in calmodulin (CaM) activation, providing a mechanism for the effective gating of synaptic plasticity induction. This provides a common mechanism for the regulation of synaptic plasticity by neuromodulators.

Degenerate boundaries for multiple-alternative decisions.

Integration-to-threshold models of two-choice perceptual decision making have guided our understanding of human and animal behavior and neural processing. Although such models seem to extend naturally to multiple-choice decision making, consensus on a normative framework has yet to emerge, and hence the implications of threshold characteristics for multiple choices have only been partially explored. Here we consider sequential Bayesian inference and a conceptualisation of decision making as a particle diffusing in n-dimensions. We show by simulation that, within a parameterised subset of time-independent boundaries, the optimal decision boundaries comprise a degenerate family of nonlinear structures that jointly depend on the state of multiple accumulators and speed-accuracy trade-offs. This degeneracy is contrary to current 2-choice results where there is a single optimal threshold. Such boundaries support both stationary and collapsing thresholds as optimal strategies for decision-making, both of which result from stationary representations of nonlinear boundaries. Our findings point towards a normative theory of multiple-choice decision making, provide a characterisation of optimal decision thresholds under this framework, and inform the debate between stationary and dynamic decision boundaries for optimal decision making.

Artificial SA-I and RA-I afferents for tactile sensing of ridges and gratings.

For robot touch to reach the capabilities of human touch, artificial tactile sensors may require transduction principles like those of natural tactile afferents. Here we propose that a biomimetic tactile sensor (the TacTip) could provide suitable artificial analogues of the tactile skin dynamics, afferent responses and population encoding. Our three-dimensionally printed sensor skin is based on the physiology of the dermal-epidermal interface with an underlying mesh of biomimetic intermediate ridges and dermal papillae, comprising inner pins tipped with markers. Slowly adapting SA-I activity is modelled by marker displacements and rapidly adapting RA-I activity by marker speeds. We test the biological plausibility of these artificial population codes with three classic experiments used for natural touch: (1a) responses to normal pressure to test adaptation of single afferents and spatial modulation across the population; (1b) responses to bars, edges and gratings to compare with measurements from monkey primary afferents; and (2) discrimination of grating orientation to compare with human perceptual performance. Our results show a match between artificial and natural touch at single afferent, population and perceptual levels. As expected, natural skin is more sensitive, which raises a challenge to fabricate a biomimetic fingertip that demonstrates human sensitivity using the transduction principles of human touch.