Use of r(+)-n-propargyl-1-aminoindan to treat or prevent hearing loss

A method of treating or inhibiting hearing loss in a mammalian subject, comprising administering to the subject an amount of R(+)-N-propargyl-1-aminoindan or pharmaceutically acceptable salt thereof effective to treat or inhibit the hearing loss in the subject

Effects of Extra Dimensions on Unitarity and Higgs Boson Mass

We study the unitarity constraint on the two body Higgs boson elastic scattering in the presence of extra dimensions. The contributions from exchange of spin-2 and spin-0 Kaluza-Klein states can have large effect on the partial wave amplitude. Unitarity condition restrict the maximal allowed value for the ratio $r$ of the center of mass energy to the gravity scale to be less than one. Although the constraint on the standard Higgs boson mass for $r$ of order one is considerably relaxed, for small $r$ the constraint is similar to that in the Standard Model. The resulting bound on the Higgs boson mass is not dramatically altered if perturbative calculations are required to be valid up to the maximal allowed value for $r$.Comment: References added, RevTex, 9 pages with two figure

Distance-Dependent Scaling of Calcium Transients Evoked by Backpropagating Spikes and Synaptic Activity in Dendrites of Hippocampal Interneurons

Although interactions between backpropagating action potentials and synaptic stimulations have been extensively studied in pyramidal neurons, dendritic propagation and the summation of these signals in interneurons are not nearly as well known. In this study, twophoton imaging was used to explore the basic properties of dendritic calcium signaling in CA1 stratum radiatum interneurons. In contrast to hippocampal pyramidal neurons, the backpropagating action potential-evoked calcium transients in dendrites of interneurons underwent a distance-dependent increment. Although, in proximal dendrites, an increment could be attributed to a smaller dendrite diameter, distal dendrites did not show such dependence. Calcium responses in interneurons had a smaller amplitude, slower rise time, and decay than in pyramidal neurons. To explore the factors underlying the difference, we compared the calcium-binding capacity in interneurons and in pyramidal neurons. Our finding that endogenous calcium buffers had a higher level in interneurons may primarily explain the different kinetics and amplitudes of calcium transients. Synaptic stimulation-evoked calcium transients were also larger at distant dendritic locations. The spread of these signals was restricted to 12–13 m long dendritic compartments. Supporting the reported lack of long-term potentiation in these interneurons, we found only sublinear or linear summations of calcium responses to coincident synaptic inputs and backpropagating spikes

5-HT6/7 receptor antagonists facilitate dopamine release in the cochlea via a GABAergic disinhibitory mechanism

In humans, serotonin (5-HT) has been implicated in numerous physiological and pathological processes in the peripheral auditory system. Dopamine (DA), another transmitter of the lateral olivocochlear (LOC) efferents making synapses on cochlear nerve dendrites, controls auditory nerve activation and protects the sensory nerve against overactivation. Using in vitro microvolume superfusion techniques we tested 5-HT6 and 5-HT7 receptor antagonists whether they can influence dopamine (DA) release from the guinea-pig cochlea in control and in ischemic conditions using currently available and new 5-HT6 and 5-HT7 antagonists and mixed antagonists, which were synthesized and characterized for the current study. While the 5-HT7 antagonist SB-258719 was ineffective, SB-271046, which blocks the 5-HT6 receptor, caused a significant increase in cochlear DA release what is contradictory with the excitatory nature of this type of receptor. Moreover, the mixed 5-HT6/7 antagonist EGIS-12233 induced an even more pronounced increase in the resting DA release. To understand why the block of an excitatory receptor results in an increase instead of a decrease in function, we investigated the possible involvement of an indirect neural mechanism through an inhibitory system. In the presence of the GABA(A) receptor blocker bicuculline, EGIS-12233 failed to increase the release of DA, suggesting that the serotonin receptor modulation of DA release from the lateral olivocochlear efferents in the cochlea was produced indirectly by decreasing the GABAergic inhibitory tone on dopaminergic nerve endings. The mixed 5-HT7/D-4 receptor antagonist EGIS-11983 significantly increased both the stimulation-evoked and the resting DA release, while the selective D4 blocker L-741,741 alone had no significant effect. Ischemia, simulated by oxygen and glucose deprivation from the perfusion solution had no action on the effect of the drugs. Drugs that can increase the release of DA from LOC terminals in the cochlea may have a role in the treatment of sensorineural hearing loss

Imaging high-resolution structure of GFP-expressing neurons in neocortex in vivo

To detect subtle changes in neuronal morphology in response to changes in experience, one must image neurons at high resolution in vivo over time scales of minutes to days. We accomplished this by infecting postmitotic neurons in rat and mouse barrel cortex with a Sindbis virus carrying the gene for enhanced green fluorescent protein. Visualized with 2-photon excitation laser scanning microscopy, infected neurons showed bright fluorescence that was distributed homogeneously throughout the cell, including axonal and dendritic arbors. Single dendritic spines could routinely be resolved and their morphological dynamics visualized. Viral infection and imaging were achieved throughout postnatal development up to early adulthood (P 8–30), although the viral efficiency of infection decreased with age. This relatively noninvasive method for fluorescent labeling and imaging of neurons allows the study of morphological dynamics of neocortical neurons and their circuits in vivo