Can ecosystem-based deep-sea fishing be sustained?

Can there ever be a truly sustainable deep-sea fishery and if so, where and under what conditions? Ecosystembased fisheries management requires that this question be addressed such that habitat, bycatch species, and targeted fish populations are considered together within an ecosystem context. To this end, we convened the first workshop to develop an ecosystem approach to deep-sea fisheries and to ask whether deep-sea species could be fished sustainably. The workshop participants were able to integrate bycatch information into their framework but found it more difficult to integrate other ecosystem indicators such as habitat characteristics. (First two paragraphs from the Executive Summary

synaptojanin1 Is Required for Temporal Fidelity of Synaptic Transmission in Hair Cells

To faithfully encode mechanosensory information, auditory/vestibular hair cells utilize graded synaptic vesicle (SV) release at specialized ribbon synapses. The molecular basis of SV release and consequent recycling of membrane in hair cells has not been fully explored. Here, we report that comet, a gene identified in an ENU mutagenesis screen for zebrafish larvae with vestibular defects, encodes the lipid phosphatase Synaptojanin 1 (Synj1). Examination of mutant synj1 hair cells revealed basal blebbing near ribbons that was dependent on Cav1.3 calcium channel activity but not mechanotransduction. Synaptojanin has been previously implicated in SV recycling; therefore, we tested synaptic transmission at hair-cell synapses. Recordings of post-synaptic activity in synj1 mutants showed relatively normal spike rates when hair cells were mechanically stimulated for a short period of time at 20 Hz. In contrast, a sharp decline in the rate of firing occurred during prolonged stimulation at 20 Hz or stimulation at a higher frequency of 60 Hz. The decline in spike rate suggested that fewer vesicles were available for release. Consistent with this result, we observed that stimulated mutant hair cells had decreased numbers of tethered and reserve-pool vesicles in comparison to wild-type hair cells. Furthermore, stimulation at 60 Hz impaired phase locking of the postsynaptic activity to the mechanical stimulus. Following prolonged stimulation at 60 Hz, we also found that mutant synj1 hair cells displayed a striking delay in the recovery of spontaneous activity. Collectively, the data suggest that Synj1 is critical for retrieval of membrane in order to maintain the quantity, timing of fusion, and spontaneous release properties of SVs at hair-cell ribbon synapses

Active zone proteins are dynamically associated with synaptic ribbons in rat pinealocytes

Synaptic ribbons (SRs) are prominent organelles that are abundant in the ribbon synapses of sensory neurons where they represent a specialization of the cytomatrix at the active zone (CAZ). SRs occur not only in neurons, but also in neuroendocrine pinealocytes where their function is still obscure. In this study, we report that pinealocyte SRs are associated with CAZ proteins such as Bassoon, Piccolo, CtBP1, Munc13–1, and the motorprotein KIF3A and, therefore, consist of a protein complex that resembles the ribbon complex of retinal and other sensory ribbon synapses. The pinealocyte ribbon complex is biochemically dynamic. Its protein composition changes in favor of Bassoon, Piccolo, and Munc13–1 at night and in favor of KIF3A during the day, whereas CtBP1 is equally present during the night and day. The diurnal dynamics of the ribbon complex persist under constant darkness and decrease after stimulus deprivation of the pineal gland by constant light. Our findings indicate that neuroendocrine pinealocytes possess a protein complex that resembles the CAZ of ribbon synapses in sensory organs and whose dynamics are under circadian regulation

Structure and Function of the Hair Cell Ribbon Synapse

Faithful information transfer at the hair cell afferent synapse requires synaptic transmission to be both reliable and temporally precise. The release of neurotransmitter must exhibit both rapid on and off kinetics to accurately follow acoustic stimuli with a periodicity of 1 ms or less. To ensure such remarkable temporal fidelity, the cochlear hair cell afferent synapse undoubtedly relies on unique cellular and molecular specializations. While the electron microscopy hallmark of the hair cell afferent synapse — the electron-dense synaptic ribbon or synaptic body — has been recognized for decades, dissection of the synapse’s molecular make-up has only just begun. Recent cell physiology studies have added important insights into the synaptic mechanisms underlying fidelity and reliability of sound coding. The presence of the synaptic ribbon links afferent synapses of cochlear and vestibular hair cells to photoreceptors and bipolar neurons of the retina. This review focuses on major advances in understanding the hair cell afferent synapse molecular anatomy and function that have been achieved during the past years

Mice with altered KCNQ4 K+ channels implicate sensory outer hair cells in human progressive deafness

KCNQ4 is an M-type K+ channel expressed in sensory hair cells of the inner ear and in the central auditory pathway. KCNQ4 mutations underlie human DFNA2 dominant progressive hearing loss. We now generated mice in which the KCNQ4 gene was disrupted or carried a dominant negative DFNA2 mutation. Although KCNQ4 is strongly expressed in vestibular hair cells, vestibular function appeared normal. Auditory function was only slightly impaired initially. It then declined over several weeks in Kcnq4-/- mice and over several months in mice carrying the dominant negative allele. This progressive hearing loss was paralleled by a selective degeneration of outer hair cells (OHCs). KCNQ4 disruption abolished the I(K,n) current of OHCs. The ensuing depolarization of OHCs impaired sound amplification. Inner hair cells and their afferent synapses remained mostly intact. These cells were only slightly depolarized and showed near-normal presynaptic function. We conclude that the hearing loss in DFNA2 is predominantly caused by a slow degeneration of OHCs resulting from chronic depolarization

Mausmutanten mit veränderten afferenten Synapsen der inneren Haarzellen als Tiermodelle der auditorischen Neuropathie

Die perisynaptische Audiopathie (auditorische Neuropathie) ist durch das Vorhandensein von otoakustischen Emissionen bei pathologischen auditorisch evozierten Potentialen gekennzeichnet. Die ursächlichen Pathomechanismen sind noch weitgehend unklar. Es könnte sich sowohl um Störungen des Hörvorganges im Bereich der inneren Haarzellen (IHZ), ihrer afferenten Synapsen oder des Hörnervs handeln . Die Charakterisierung der Pathomechanismen ist durch den Mangel an spezifischen audiologischen Tests, die zwischen Dysfunktionen an den genannten Strukturen unterscheiden könnten, limitiert. Wir untersuchen die Funktion der afferenten Synapse normaler und schwerhöriger Mäuse mit morphologischen sowie zell- und systemphysiologischen Methoden. Die zwei hier vorgestellten Tiermodelle, die Bassoon (synaptisches Protein) Mausmutante und die CaV1.3 (Ca2+ Kanal) Knockout-Maus, zeigen eine hochgradige Schwerhörigkeit bzw. Taubheit. In beiden Fällen liegt eine Dysfunktion der inneren Haarzelle und ihrer Synapsen vor, denen die synaptischen Bänder fehlen. Während in der CaV1.3 KO-Maus Depolarisationen wegen des fehlenden Ca2+-Einstroms auch bei langen Stimuli kaum Exozytose induzierten, beobachteten wir in den Bassoon-Mutanten nur einen selektiven Verlust der schnell freisetzbaren Vesikelpopulation (Readily Releasable Pool, RRP). Dieser Verlust des RRP führte zu einer pantonalen Anhebung der CAP-Schwelle um 50 dB

Tmprss3 loss of function impairs cochlear inner hair cell Kcnma1 channel membrane expression

Before acquiring their mature state, cochlear hair cells undergo a series of changes in expression of ion channels. How this complex mechanism is achieved is not fully understood. Tmprss3, a type II serine protease expressed in hair cells, is required for their proper functioning at the onset of hearing. To unravel the role of Tmprss3 in the acquisition of mature K+ currents, we compared their function by patch-clamp technique in wild-type Tmprss3WT and Tmprss3Y260X-mutant mice. Interestingly, only outward K+ currents were altered in Tmprss3Y260X-mutant mice. To determine by which mechanism this occurred, we compared the protein network of Tmprss3WT and Tmprss3Y260X-mutant mice using proteomic analysis. This led to the identification of a pathway related to potassium Kcnma1 channels. This pathway was validated by immunohistochemistry, focusing on the most downregulated protein that was identified as a cochlear Kcnma1-associated protein, APOA1. Finally, we show that, in contrast to Tmprss3WT, Kcnma1 channels were absent at the neck of inner hair cells (IHCs) in Tmprss3Y260X-mutant mice. In conclusion, our data suggest that lack of Tmprss3 leads to a decrease in Kcnma1 potassium channels expression in (IHCs).Laurence Molina, Lydie Fasquelle, Régis Nouvian, Nicolas Salvetat, Hamish S. Scott, Michel Guipponi, Franck Molina, Jean-Luc Puel and Benjamin Delpra