Autonomous Flying With Neuromorphic Sensing.

Autonomous flight for large aircraft appears to be within our reach. However, launching autonomous systems for everyday missions still requires an immense interdisciplinary research effort supported by pointed policies and funding. We believe that concerted endeavors in the fields of neuroscience, mathematics, sensor physics, robotics, and computer science are needed to address remaining crucial scientific challenges. In this paper, we argue for a bio-inspired approach to solve autonomous flying challenges, outline the frontier of sensing, data processing, and flight control within a neuromorphic paradigm, and chart directions of research needed to achieve operational capabilities comparable to those we observe in nature. One central problem of neuromorphic computing is learning. In biological systems, learning is achieved by adaptive and relativistic information acquisition characterized by near-continuous information retrieval with variable rates and sparsity. This results in both energy and computational resource savings being an inspiration for autonomous systems. We consider pertinent features of insect, bat and bird flight behavior as examples to address various vital aspects of autonomous flight. Insects exhibit sophisticated flight dynamics with comparatively reduced complexity of the brain. They represent excellent objects for the study of navigation and flight control. Bats and birds enable more complex models of attention and point to the importance of active sensing for conducting more complex missions. The implementation of neuromorphic paradigms for autonomous flight will require fundamental changes in both traditional hardware and software. We provide recommendations for sensor hardware and processing algorithm development to enable energy efficient and computationally effective flight control.

Harmonin enhances voltage-dependent facilitation of Cav1.3 channels and synchronous exocytosis in mouse inner hair cells.

Cav1.3 channels mediate Ca(2+) influx that triggers exocytosis of glutamate at cochlear inner hair cell (IHC) synapses. Harmonin is a PDZ-domain-containing protein that interacts with the C-terminus of the Cav1.3 α1 subunit (α11.3) and controls cell surface Cav1.3 levels by promoting ubiquitin-dependent proteosomal degradation. However, PDZ-domain-containing proteins have diverse functions and regulate other Cav1.3 properties, which could collectively influence presynaptic transmitter release. Here, we report that harmonin binding to the α11.3 distal C-terminus (dCT) enhances voltage-dependent facilitation (VDF) of Cav1.3 currents both in transfected HEK293T cells and in mouse inner hair cells. In HEK293T cells, this effect of harmonin was greater for Cav1.3 channels containing the auxiliary Cav ß1 than with the ß2 auxiliary subunit. Cav1.3 channels lacking the α11.3 dCT were insensitive to harmonin modulation. Moreover, the 'deaf-circler' dfcr mutant form of harmonin, which does not interact with the α11.3 dCT, did not promote VDF. In mature IHCs from mice expressing the dfcr harmonin mutant, Cav1.3 VDF was less than in control IHCs. This difference was not observed between control and dfcr IHCs prior to hearing onset. Membrane capacitance recordings from dfcr IHCs revealed a role for harmonin in synchronous exocytosis and in increasing the efficiency of Ca(2+) influx for triggering exocytosis. Collectively, our results indicate a multifaceted presynaptic role of harmonin in IHCs in regulating Cav1.3 Ca(2+) channels and exocytosis.

Protein phosphatase 2A dephosphorylates CaBP4 and regulates CaBP4 function.

PURPOSE: CaBP4 is a neuronal Ca(2+)-binding protein that is expressed in the retina and in the cochlea, and is essential for normal photoreceptor synaptic function. CaBP4 is phosphorylated by protein kinase C zeta (PKCζ) in the retina at serine 37, which affects its interaction with and modulation of voltage-gated Ca(v)1 Ca(2+) channels. In this study, we investigated the potential role and functional significance of protein phosphatase 2A (PP2A) in CaBP4 dephosphorylation. METHODS: The effect of protein phosphatase inhibitors, light, and overexpression of PP2A subunits on CaBP4 dephosphorylation was measured in in vitro assays. Pull-down experiments using retinal or transfected HEK293 cell lysates were used to investigate the association between CaBP4 and PP2A subunits. Electrophysiologic recordings of cotransfected HEK293 cells were performed to analyze the effect of CaBP4 dephosphorylation in modulating Ca(v)1.3 currents. RESULTS: PP2A inhibitors, okadaic acid (OA), and fostriecin, but not PP1 selective inhibitors, NIPP-1, and inhibitor 2, block CaBP4 dephosphorylation in retinal lysates. Increased phosphatase activity in light-dependent conditions reverses phosphorylation of CaBP4 by PKCζ. In HEK293 cells, overexpression of PP2A enhances the rate of dephosphorylation of CaBP4. In addition, inhibition of protein phosphatase activity by OA increases CaBP4 phosphorylation and potentiates the modulatory effect of CaBP4 on Ca(v)1.3 Ca(2+) channels in HEK293T cells. CONCLUSIONS: This study provides evidence that CaBP4 is dephosphorylated by PP2A in the retina. Our findings reveal a novel role for protein phosphatases in regulating CaBP4 function in the retina, which may fine tune presynaptic Ca(2+) signals at the photoreceptor synapse.

Harmonin inhibits presynaptic Cav1.3 Ca²âº channels in mouse inner hair cells.

Harmonin is a scaffolding protein that is required for normal mechanosensory function in hair cells. We found a presynaptic association of harmonin and Ca(v)1.3 Ca(2+) channels at the mouse inner hair cell synapse, which limits channel availability through a ubiquitin-dependent pathway.

Evidence that fast exocytosis can be predominantly mediated by vesicles not docked at active zones in frog saccular hair cells.

The prevailing model of neurotransmitter release stipulates that Ca2+ influx triggers the rapid fusion of vesicles that are docked at presynaptic active zones. Under this model, slower tonic release is supported by vesicles clustered nearby that have to translocate to the release sites before fusion. We have examined this hypothesis at the afferent synapse of saccular hair cells of the leopard frog, Rana pipiens. Detailed morphological measurements at this ribbon synapse show that on average 32 vesicles are docked at each active zone. We show that at this 'graded' synapse, depolarization produces an exocytotic 'burst' that is largely complete within 20 ms after fusion of 280 vesicles per active zone, almost an order of magnitude more than expected. Recovery from paired pulse depression occurs with a time constant of 29 ms, indicating that replenishment of this fast-fusing pool of vesicles is also fast. Our results suggest that non-docked vesicles are capable of fast fusion and that these vesicles constitute the vast majority of the fast-fusing pool. The view that the population of fast-fusing presynaptic vesicles is limited to docked vesicles therefore requires re-evaluation. We propose that compound fusion, i.e. the fusion of vesicles with each other before and/or after they fuse with the membrane can explain multivesicular release at this synapse.