Cholinergic efferent synaptic transmission regulates the maturation of auditory hair cell ribbon synapses.

Spontaneous electrical activity generated by developing sensory cells and neurons is crucial for the maturation of neural circuits. The full maturation of mammalian auditory inner hair cells (IHCs) depends on patterns of spontaneous action potentials during a 'critical period' of development. The intrinsic spiking activity of IHCs can be modulated by inhibitory input from cholinergic efferent fibres descending from the brainstem, which transiently innervate immature IHCs. However, it remains unknown whether this transient efferent input to developing IHCs is required for their functional maturation. We used a mouse model that lacks the α9-nicotinic acetylcholine receptor subunit (α9nAChR) in IHCs and another lacking synaptotagmin-2 in the efferent terminals to remove or reduce efferent input to IHCs, respectively. We found that the efferent system is required for the developmental linearization of the Ca(2+)-sensitivity of vesicle fusion at IHC ribbon synapses, without affecting their general cell development. This provides the first direct evidence that the efferent system, by modulating IHC electrical activity, is required for the maturation of the IHC synaptic machinery. The central control of sensory cell development is unique among sensory systems

Parity nonconservation in heavy atoms: The radiative correction enhanced by the strong electric field of the nucleus

Parity nonconservation due to the nuclear weak charge is considered. We demonstrate that the radiative corrections to this effect due to the vacuum fluctuations of the characteristic size larger than the nuclear radius $r_0$ and smaller than the electron Compton wave-length $\lambda_C$ are enhanced because of the strong electric field of the nucleus. The parameter that allows one to classify the corrections is the large logarithm $\ln(\lambda_C/r_0)$. The vacuum polarization contribution is enhanced by the second power of the logarithm. Although the self-energy and the vertex corrections do not vanish, they contain only the first power of the logarithm. The value of the radiative correction is 0.4% for Cs and 0.9% for Tl, Pb, and Bi. We discuss also how the correction affects the interpretation of the experimental data on parity nonconservation in atoms.Comment: 4 pages, 3 figures, RevTe

Reevaluation of the role of nuclear uncertainties in experiments on atomic parity violation with isotopic chains

In light of new data on neutron distributions from experiments with antiprotonic atoms [ Trzcinska {\it et al.}, Phys. Rev. Lett. 87, 082501 (2001)], we reexamine the role of nuclear-structure uncertainties in the interpretation of measurements of parity violation in atoms using chains of isotopes of the same element. With these new nuclear data, we find an improvement in the sensitivity of isotopic chain measurements to ``new physics'' beyond the standard model. We compare possible constraints on ``new physics'' with the most accurate to date single-isotope probe of parity violation in the Cs atom. We conclude that presently isotopic chain experiments employing atoms with nuclear charges Z < 50 may result in more accurate tests of the weak interaction.Comment: 6 pages, 1 fig., submitted to Phys. Rev.

High-spin study of rotational structures in 72Br

High-spin states in 3572Br37 were studied using the 40Ca(36Ar, 3pn) reaction. The existing level scheme has been significantly modified and extended. Evidence has been found for a spin reassignment of -1ℏh to the previously observed negative-parity band, which carries implications for the interpretation of a signature inversion in this structure. One signature of the previously assigned positive-parity band is interpreted as negative parity and has been extended to I π=(22-) and its signature partner has been observed up to Iπ = (19-) for the first time. The remaining positive-parity band has been extended to Iπ=(29+). A sequence of states observed to Iπ=(22+) may be the signature partner of this structure. Configurations have been assigned to each of these three structures through comparisons to cranked Nilsson-Strutinsky calculations

Developmental regulation of nicotinic synapses on cochlear inner hair cells

In the mature cochlea, inner hair cells (IHCs) transduce acoustic signals into receptor potentials, communicating to the brain by synaptic contacts with afferent fibers. Before the onset of hearing, a transient efferent innervation is found on IHCs, mediated by a nicotinic cholinergic receptor that may contain both α9 and α10 subunits. Calcium influx through that receptor activates calcium-dependent (SK2-containing) potassium channels. This inhibitory synapse is thought to disappear after the onset of hearing &#91;after postnatal day 12 (P12)&#93;. We documented this developmental transition using whole-cell recordings from IHCs in apical turns of the rat organ of Corti. Acetylcholine elicited ionic currents in 88-100% of IHCs between P3 and P14, but in only 1 of 11 IHCs at P16-P22. Potassium depolarization of efferent terminals caused IPSCs in 67% of IHCs at P3, in 100% at P7-P9, in 93% at P10-P12, but in only 40% at P13-P14 and in none of the IHCs tested between P16 and P22. Earlier work had shown by in situ hybridization that α9 mRNA is expressed in adult IHCs but that α10 mRNA disappears after the onset of hearing. In the present study, antibodies to α10 and to the associated calcium-dependent (SK2) potassium channel showed a similar developmental loss. The correlated expression of these gene products with functional innervation suggests that Alpha10 and SK2, but not Alpha9, are regulated by synaptic activity. Furthermore, this developmental knock-out of α10, but not α9, supports the hypothesis that functional nicotinic acetylcholine receptors in hair cells are heteromers containing both these subunits.Fil:Katz, E. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina.Fil:Gómez-Casati, M.E. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina

Constitutive expression of the α10 nicotinic acetylcholine receptor subunit fails to maintain cholinergic responses in inner hair cells after the onset of hearing

Efferent inhibition of cochlear hair cells is mediated by α9α10 nicotinic cholinergic receptors (nAChRs) functionally coupled to calcium-activated, small conductance (SK2) potassium channels. Before the onset of hearing, efferent fibers transiently make functional cholinergic synapses with inner hair cells (IHCs). The retraction of these fibers after the onset of hearing correlates with the cessation of transcription of the Chrna10 (but not the Chrna9) gene in IHCs. To further analyze this developmental change, we generated a transgenic mice whose IHCs constitutively express α10 into adulthood by expressing the α10 cDNA under the control of the Pou4f3 gene promoter. In situ hybridization showed that the α10 mRNA is expressed in IHCs of 8-week-old transgenic mice, but not in wild-type mice. Moreover, this mRNA is translated into a functional protein, since IHCs from P8-P10 α10 transgenic mice backcrossed to a Chrna10 -/- background (whose IHCs have no cholinergic function) displayed normal synaptic and acetylcholine (ACh)-evoked currents in patch-clamp recordings. Thus, the α10 transgene restored nAChR function. However, in the α10 transgenic mice, no synaptic or ACh-evoked currents were observed in P16-18 IHCs, indicating developmental down-regulation of functional nAChRs after the onset of hearing, as normally observed in wild-type mice. The lack of functional ACh currents correlated with the lack of SK2 currents. These results indicate that multiple features of the efferent postsynaptic complex to IHCs, in addition to the nAChR subunits, are down-regulated in synchrony after the onset of hearing, leading to lack of responses to ACh. © 2009 Association for Research in Otolaryngology.Fil:Taranda, J. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina.Fil:Ballestero, J.A. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina.Fil:Wedemeyer, C. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina.Fil:Gómez-Casati, M.E. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina.Fil:Lipovsek, M. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina.Fil:Katz, E. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina