Synthesis of 2-(pyridin-3-yl)-1-azabicyclo[3.2.2]nonane, 2-(pyridin-3-yl)-1-azabicyclo[2.2.2]octane, and 2-(pyridin-3-yl)-1-azabicyclo[3.2.1]octane, a class of potent nicotinic acetylcholine receptor-ligands.

In an attempt to generate nicotinic acetylcholine receptor (nAChR) ligands selective for the alpha4beta2 and alpha7 subtype receptors we designed and synthesized constrained versions of anabasine, a naturally occurring nAChR ligand. 2-(Pyridin-3-yl)-1-azabicyclo[2.2.

A mechano-electro-acoustical model for the cochlea: response to acoustic stimuli.

A linear, physiologically based, three-dimensional finite element model of the cochlea is developed. The model integrates the electrical, acoustic, and mechanical elements of the cochlea. In particular, the model includes interactions between structures in the organ of Corti (OoC), piezoelectric relations for outer hair cell (OHC) motility, hair bundle (HB) conductance that changes with HB deflection, current flow in the cross section and along the different scalae, and the feed-forward effect.

Chlorpromazine alters cochlear mechanics and amplification: in vivo evidence for a role of stiffness modulation in the organ of corti.

Although prestin-mediated outer hair cell (OHC) electromotility provides mechanical force for sound amplification in the mammalian cochlea, proper OHC stiffness is required to maintain normal electromotility and to transmit mechanical force to the basilar membrane (BM). To investigate the in vivo role of OHC stiffness in cochlear amplification, chlorpromazine (CPZ), an antipsychotic drug that alters OHC lateral wall biophysics, was infused into the cochleae in living guinea pigs. The effects of CPZ on cochlear amplification and OHC electromotility were observed by measuring the acoustically and electrically evoked BM motions.

Plified nonlinear outer hair cell models.

We present a consistent second-order expansion of nonlinear constitutive theories for outer hair cells. For a particular theory, we will test the validity of such a model for small variations in voltage and strain about the resting state of outer hair cells. An analysis of the various terms in the simplified nonlinear model and their relevance to outer hair cell mechanics are presented.

Two-state model for outer hair cell stiffness and motility.

With discovery of the protein prestin and the gathering evidence linking it to outer hair cell electromotility, the working mechanism of outer hair cells is becoming clearer. Recent experiments have established the voltage-dependent stiffness of outer hair cells and given an insight into the nature of variation of stiffness with respect to voltage. These and earlier experiments are used to analyze and develop models of outer hair cell response.