Anat Kahan

Photoreactivity of a Push-Pull Merocyanine in Static Electric Fields: A Three-State Model of Isomerization Reactions Involving Conical Intersections

The photochemistry of a prototype push-pull merocyanine is discussed using a simple three-state model. As a derivative of butadiene, the model focuses on two isomerization reactions around the two double bonds of the butadiene backbone. As a molecule substituted by an electron donor and electron acceptor at opposite ends, its structure as well as its photochemistry are expected to be strongly affected by the environment. In polar solvents, a zwitterion transition state for each of the isomerization reactions is stabilized, and its energy is on the same order as that of the biradical one; this leads to the symmetry allowed crossing (S(0)/S(1) conical intersection). It is shown that applying an external electric field or varying the solvent polarity changes the relative energies of the different transition states as well as that of the conical intersection, and thus different photochemical products can be obtained. In particular, the very existence of conical intersections is found to depend on these external parameters. This work provides a theoretical foundation for ideas expressed by Squillacote et al. (J. Am. Chem. Soc. 2004, 126, 1940) concerning the electrostatic control of photochemical reactions.

Extracellular pH Regulates Excitability of Vomeronasal Sensory Neurons

The mouse vomeronasal organ (VNO) plays a critical role in semiochemical detection and social communication. Vomeronasal stimuli are typically secreted in various body fluids. Following direct contact with urine deposits or other secretions, a peristaltic vascular pump mediates fluid entry into the recipients VNO. Therefore, while vomeronasal sensory neurons (VSNs) sample various stimulatory semiochemicals dissolved in the intraluminal mucus, they might also be affected by the general physicochemical properties of the “solvent.” Here, we report cycle stage-correlated variations in urinary pH among female mice. Estrus-specific pH decline is observed exclusively in urine samples from sexually experienced females. Moreover, patch-clamp recordings in acute VNO slices reveal that mouse VSNs reliably detect extracellular acidosis. Acid-evoked responses share the biophysical and pharmacological hallmarks of the hyperpolarization-activated current Ih. Mechanistically, VSN acid sensitivity depends on a pH-induced shift in the voltage-dependence of Ih activation that causes the opening of HCN channels at rest, thereby increasing VSN excitability. Together, our results identify extracellular acidification as a potent activator of vomeronasal Ih and suggest HCN channel-dependent vomeronasal gain control of social chemosignaling. Our data thus reveal a potential mechanistic basis for stimulus pH detection in rodent chemosensory communication.

Solvent Tuning of a Conical Intersection: Direct Experimental Verification of a Theoretical Prediction

We report an ultrafast study of a merocyanine molecule, whose fluorescence lifetime was tuned by changing the solvents polarity. A recent theoretical prediction that the fluorescence lifetime is considerably shortened upon lowering the polarity of the solvent, due to tuning of the conical intersection properties, is fully confirmed (Xu et al. J. Phys. Chem. A 2009, 113, 9779-9791). This constitutes a direct measurement of a previously predicted tunable property of a conical intersection.

Prolonged Intracellular Na + Dynamics Govern Electrical Activity in Accessory Olfactory Bulb Mitral Cells

Persistent activity has been reported in many brain areas and is hypothesized to mediate working memory and emotional brain states and to rely upon network or biophysical feedback. Here, we demonstrate a novel mechanism by which persistent neuronal activity can be generated without feedback, relying instead on the slow removal of Na+ from neurons following bursts of activity. We show that mitral cells in the accessory olfactory bulb (AOB), which plays a major role in mammalian social behavior, may respond to a brief sensory stimulation with persistent firing. By combining electrical recordings, Ca2+ and Na+ imaging, and realistic computational modeling, we explored the mechanisms underlying the persistent activity in AOB mitral cells. We found that the exceptionally slow inward current that underlies this activity is governed by prolonged dynamics of intracellular Na+ ([Na+]i), which affects neuronal electrical activity via several pathways. Specifically, elevated dendritic [Na+]i reverses the Na+-Ca2+ exchanger activity, thus modifying the [Ca2+]i set-point. This process, which relies on ubiquitous membrane mechanisms, is likely to play a role in other neuronal types in various brain regions.

Interdependent Conductances Drive Infraslow Intrinsic Rhythmogenesis in a Subset of Accessory Olfactory Bulb Projection Neurons

The accessory olfactory system controls social and sexual behavior. However, key aspects of sensory signaling along the accessory olfactory pathway remain largely unknown. Here, we investigate patterns of spontaneous neuronal activity in mouse accessory olfactory bulb mitral cells, the direct neural link between vomeronasal sensory input and limbic output. Both in vitro and in vivo, we identify a subpopulation of mitral cells that exhibit slow stereotypical rhythmic discharge. In intrinsically rhythmogenic neurons, these periodic activity patterns are maintained in absence of fast synaptic drive. The physiological mechanism underlying mitral cell autorhythmicity involves cyclic activation of three interdependent ionic conductances: subthreshold persistent Na+ current, R-type Ca2+ current, and Ca2+-activated big conductance K+ current. Together, the interplay of these distinct conductances triggers infraslow intrinsic oscillations with remarkable periodicity, a default output state likely to affect sensory processing in limbic circuits. SIGNIFICANCE STATEMENT We show for the first time that some rodent accessory olfactory bulb mitral cells—the direct link between vomeronasal sensory input and limbic output—are intrinsically rhythmogenic. Driven by ≥3 distinct interdependent ionic conductances, infraslow intrinsic oscillations show remarkable periodicity both in vitro and in vivo. As a novel default state, infraslow autorhythmicity is likely to affect limbic processing of pheromonal information.

Extracting Behaviorally Relevant Traits from Natural Stimuli: Benefits of Combinatorial Representations at the Accessory Olfactory Bulb

For many animals, chemosensation is essential for guiding social behavior. However, because multiple factors can modulate levels of individual chemical cues, deriving information about other individuals via natural chemical stimuli involves considerable challenges. How social information is extracted despite these sources of variability is poorly understood. The vomeronasal system provides an excellent opportunity to study this topic due to its role in detecting socially relevant traits. Here, we focus on two such traits: a female mouse’s strain and reproductive state. In particular, we measure stimulus-induced neuronal activity in the accessory olfactory bulb (AOB) in response to various dilutions of urine, vaginal secretions, and saliva, from estrus and non-estrus female mice from two different strains. We first show that all tested secretions provide information about a female’s receptivity and genotype. Next, we investigate how these traits can be decoded from neuronal activity despite multiple sources of variability. We show that individual neurons are limited in their capacity to allow trait classification across multiple sources of variability. However, simple linear classifiers sampling neuronal activity from small neuronal ensembles can provide a substantial improvement over that attained with individual units. Furthermore, we show that some traits are more efficiently detected than others, and that particular secretions may be optimized for conveying information about specific traits. Across all tested stimulus sources, discrimination between strains is more accurate than discrimination of receptivity, and detection of receptivity is more accurate with vaginal secretions than with urine. Our findings highlight the challenges of chemosensory processing of natural stimuli, and suggest that downstream readout stages decode multiple behaviorally relevant traits by sampling information from distinct but overlapping populations of AOB neurons.

Photophysics of (1-butyl-4-(1H-inden-1-ylidene)-1,4-dihydropyridine (BIDP): an experimental test for conical intersections.

Fluorescence experiments on (1-butyl-4-(1H-inden-1-ylidene)-1,4-dihydropyridine (BIDP) are reported in liquid and glassy solutions. The data indicate a fast decay in the fluid nonpolar, nonprotic solutions (decay times approximately 10(-12) s) and rapid but considerably slower decay in polar ones. In frozen solutions (polar and nonpolar), the fluorescence quantum yield is much higher (near 0.5 and around 0.1 in polar and nonpolar glasses, respectively). The rapid nonradiative transitions in fluid solutions are assigned to internal conversion in both solvent classes, as intersystem crossing is much slower and no net reaction is observed. These results are in agreement with predictions made for the closely related (in terms of electronic structure) but simpler molecule cyclopentadienyl-1,4-dihydropyridine (CPDHP) for which an S1/S0 conical intersection was recently proposed [Int. J. Quant. Chem. 2005, 102, 961]. The crossing of the two lowest singlet states is calculated to vanish in polar solvents such as methyl cyanide, leading to longer lifetime of S1 of CPDHP. As BIDP has a very similar electronic structure, the model predicts a corresponding change in this larger molecule. The strong fluorescence observed in the glassy environments is rationalized by the hindering of the internal torsion required to reach the geometry of the conical intersection.

The photophysics of a polar molecule in a nonpolar cryogenic glass--the effects of dimerization on (1-butyl-4-(1H-inden-1-ylidene)-1,4-dihydropyridine (BIDP).

The first excited state of BIDP was shown in a previous communication to exhibit an ultrafast decay in fluid nonpolar, nonprotic solutions due to the presence of a S(1)/S(0) conical intersection (CI). In frozen polar and nonpolar glasses a strong fluorescence was observed, rationalized by the hindering of the internal torsion required to reach the geometry of the CI. Complete analysis of the data was hampered by some unusual observations in nonpolar glasses. In this paper we show that they can be explained by assuming dimer formation, with a formation constant of K(eq) = (4 ± 3) × 10(5) M(-1) at 83 K and ΔH(dim) = 7 ± 2 kcal/mol. A complete analysis of the spectra is presented, and fluorescence quantum yields of the monomer and dimer are reported. Efficient self-quenching is found, with a Stern Volmer constant, K(SV) = (1.5 ± 0.1) × 10(6) M(-1), assigned to static quenching. The dimer absorption spectrum was extracted from the data and is compared to Kashas exciton model and to quantum chemical (QC) calculations. The basic features of exciton splitting are reproduced by quantum mechanical calculations, but complete quantitative agreement of the QC computations with the experimental results is not attained. The previous analysis of the monomer spectra using the displaced harmonic oscillator model is extended to the more demanding conditions prevailing at cryogenic temperatures. The derived ΔH(dim) is in good agreement with other dimers formation enthalpies and with the quantum mechanical calculation presented. The new analysis corrects τ(f) in MCHIP to 2.9 × 10(-13) s, somewhat smaller than the value reported in polar solvent in a previous communication, thereby strengthening the assumption that polarity can reduce the efficiency of CI.

Following Photoinduced Dynamics in Bacteriorhodopsin with 7 fsec Impulsive Vibrational Spectroscopy

Spectral modulations induced by 6fsec photoexcitation of bacteriorhodopsin are Fourier analyzed. Long lived undulations are assigned to ground state vibrational coherences, while possible excited state contributions are very short lived consisting mainly of HOOP motions.