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We report on strong field ionization of S- and R-propylene oxide in circularly polarized two-color laser fields. We find that the relative helicity of the two single-color laser fields affects the photoelectron circular dichroism (PECD). Further, we observe that PECD is modulated as a function of the subcycle release time of the electron. Our experimental observations are successfully described by a heuristic model based on electrons in chiral initial states, which are selectively liberated by the laser field and, after tunneling, interact with an achiral Coulomb potential. more...

Dynamical response of water exposed to x-rays is of utmost importance in a wealth of science areas. We exposed isolated water isotopologues to short x-ray pulses from a free-electron laser and detected momenta of all produced ions in coincidence. By combining experimental results and theoretical modeling, we identify significant structural dynamics with characteristic isotope effects in H2O2+, D2O2+, and HDO2+, such as asymmetric bond elongation and bond-angle opening, leading to two-body or three-body fragmentation on a timescale of a few femtoseconds. A method to disentangle the sequences of events taking place upon the consecutive absorption of two x-ray photons is described. The obtained deep look into structural properties and dynamics of dissociating water isotopologues provides essential insights into the underlying mechanisms. more...

We study strong-field ionization of molecular hydrogen in highly intense corotating two-color laser fields. The measured electron momentum distributions show alternating half rings (AHRs) that are characteristic of subcycle interference. We report on the role of the two-color field ratio for the visibility of this subcycle interference. The ratio of the peak electric field at 780 nm compared to the peak electric field at 390 nm E_{780}/E_{390} is varied from 0.037 to 0.18. We find very good agreement with the results from our semiclassical simulation. We conclude that the AHR pattern is visible if two conditions are fulfilled. First, the amplitudes of the two pathways that lead to the subcycle interference have to be similar, which is the case for low two-color field ratios E_{780}/E_{390}. Second, the phase difference of the two pathways must be strong enough to allow for destructive interference, which is the case for high two-color field ratios E_{780}/E_{390}. For typical experimental conditions, we find that two-color field ratios E_{780}/E_{390} in the range from 0.037 to 0.12 lead to good visibility of the AHR pattern. This guides future experiments to measure the Wigner time delay using holographic angular streaking of electrons. more...

Unbound electrons can experience resonant scattering and transient trapping in a molecular potential. In molecular photoemission, these shape resonances manifest as peaks in the cross section with a width of several electron volts. They depend on the details of the molecular potential and the wavelength of the photoelectron. We report experimental results on photo double-ionization which show the phenomenon of a collective two-electron resonance which occurs when the de Broglie wavelength of the dielectron quasiparticle is similar to that of a single electron exhibiting a single-electron shape resonance. more...

We present experimental data on the strong field tunnel ionization of argon in a counter-rotating two-color (CRTC) laser field. We find that the initial momentum component along the tunneling direction changes sign comparing the rising and the falling edge of the CRTC field. If the initial momentum at the tunnel exit points in the direction of the ion at the instant of tunneling, this manifests as an enhanced Coulomb interaction of the outgoing electron with its parent ion. Our conclusions are in accordance with predictions based on strong field approximation. more...

Light-matter interaction leading to photoelectron emission via the photoelectric effect illustrates the quantum nature of light. Here, the authors report the dependence of the photoelectron’s Wigner time delay on the photoelectron’s emission direction relative to the molecular axis of hydrogen in strong field tunnel-ionization. more...

We present experimental data on the strong-field ionization of the argon dimer in a co-rotating two-color laser field. We observe a subcycle interference pattern in the photoelectron momentum distribution and infer the Wigner time delay using holographic angular streaking of electrons. We find that the Wigner time delay varies by more than 400 attoseconds as a function of the electron emission direction with respect to the molecular axis. The measured time delay is found to be independent of the parity of the dimercation and is in good agreement with our theoretical model based on the ionization of an aligned atomic p orbital. more...

We report on the strong field ionization of H_{2} by a corotating two-color laser field. We measure the electron momentum distribution in coincidence with the kinetic energy release (KER) of dissociating hydrogen molecules. In addition to a characteristic half-moon structure, we observe a low-energy structure in the electron momentum distribution at a KER of about 3.5 eV. We speculate that the outgoing electron interacts with the molecular ion, despite the absence of classical recollisions under these conditions. Time-dependent density functional theory simulations support our conclusions. more...

Ultrashort x-ray pulses from free-electron lasers can efficiently charge up and trigger the full fragmentation of molecules. By coincident detection of up to five ions resulting from rapid Coulomb explosion of highly charged iodomethane, we show that the full three-dimensional equilibrium geometry of this prototypical polyatomic system can be determined from the measured ion momenta with the help of a charge buildup model. Supported by simulations of how the ion momenta would reflect specific changes in molecular bond lengths and angles, we demonstrate that Coulomb-explosion imaging with ultrashort x-ray pulses is a promising technique for recording movies of multidimensional nuclear wave packets, including hydrogen motions. more...

The ultrafast structural dynamics of water following inner-shell ionization is a crucial issue in high-energy radiation chemistry. We have exposed isolated water molecules to a short x-ray pulse from a free-electron laser and detected momenta of all produced ions in coincidence. By combining experimental results and theoretical modeling, we can image dissociation dynamics of individual molecules in unprecedented detail. We reveal significant molecular structural dynamics in H_{2}O^{2+}, such as asymmetric deformation and bond-angle opening, leading to two-body or three-body fragmentation on a timescale of a few femtoseconds. We thus reconstruct several snapshots of structural dynamics at different time intervals, which highlight dynamical patterns that are relevant as initiating steps of subsequent radiation-damage processes. more...

For a circularly polarized single-color field at a central frequency of 2ω, the final electron momentum distribution upon strong field ionization does not carry any information about the phase of the initial momentum distribution. Adding a weak, corotating, circularly polarized field at a central frequency of ω gives rise to a subcycle interference pattern [holographic angular streaking of electrons (HASE)]. This interference pattern allows for the retrieval of the derivative of the phase of the initial momentum distribution after tunneling ϕ_{off}^{′}(p_{i}). A trajectory-based semiclassical model (HASE model) is introduced which links the experimentally accessible quantities to ϕ_{off}^{′}(p_{i}). It is shown that a change in ϕ_{off}^{′} is equivalent to a displacement in position space Δx of the initial wave packet after tunneling. This offset in position space allows for an intuitive interpretation of the Wigner time delay Δτ_{W} in strong-field ionization for circularly polarized single-color fields. The influence of Coulomb interaction after tunneling is investigated quantitatively. more...

We report on a chiral observable upon ionization of a chiral molecule (methyloxirane) by a strong elliptically polarized laser field: a rotation of the photoelectron momentum distribution, which is enantiosensitive and forward/backward asymmetric. We explain this forward/backward asymmetric rotation of the count maxima to be equivalent to a dependence of the photoelectron circular dichroism on the electron emission angle in the plane of polarization. more...

Similar to the optical diffraction of light passing through a material grating, the Kapitza-Dirac effect occurs when an electron is diffracted by a standing light wave. In its original description, the effect is time independent. Here, we extended the Kapitza-Dirac effect to the time domain. By tracking the spatiotemporal evolution of a pulsed electron wave packet diffracted by a 60-femtosecond (where one femtosecond = 10 -15 seconds) standing wave pulse in a pump-probe scheme, we observed time-dependent diffraction patterns. The fringe spacing in the observed pattern differs from that generated by the conventional Kapitza-Dirac effect. By exploiting this time-resolved diffraction scheme, we can access the time evolution of the phase properties of a free electron and potentially image ionic potentials and electronic decoherences. more...

We studied strong-field multiphoton ionization of 1-iodo-2-methylbutane enantiomers with 395 nm circularly polarized laser pulses experimentally and theoretically. For randomly oriented molecules, we observe spin polarization up to about 15%, which is independent of the molecular enantiomer. Our experimental findings are explained theoretically as an intricate interplay between three contributions from HOMO, HOMO-1, and HOMO-2, which are formed of 5p-electrons of the iodine atom. For uniaxially oriented molecules, our theory demonstrates even larger spin polarization. Moreover, we predict a sizable enantiosensitive photoelectron circular dichroism of about 10%, which is different for different spin states of photoelectrons. more...

Atoms can form a molecule by sharing their electrons in binding orbitals. These electrons are entangled. Is there a way to break a molecular bond and obtain atoms in their ground state that are spatially separated and still entangled? Here, we show that it is possible to prepare these spatially separated, entangled atoms on femtosecond time scales from single oxygen molecules. The two neutral atoms are entangled in the magnetic quantum number of their valence electrons. In a time-delayed probe step, we use nonadiabatic tunneling, which is a magnetic quantum number-sensitive ionization mechanism. We find a fingerprint of entanglement in the measured ionization probability as a function of the angle between the light's quantization axis and the molecular axis. This establishes a platform for further experiments that harness the time resolution of strong-field experiments to investigate spatially separated, entangled atoms on femtosecond time scales. more...

X-Ray as well as electron diffraction are powerful tools for structure determination of molecules. Studies on randomly oriented molecules in the gas phase address cases in which molecular crystals cannot be generated or the interaction-free molecular structure is to be addressed. Such studies usually yield partial geometrical information, such as interatomic distances. Here, we present a complementary approach, which allows obtaining insight into the structure, handedness, and even detailed geometrical features of molecules in the gas phase. Our approach combines Coulomb explosion imaging, the information that is encoded in the molecular-frame diffraction pattern of core-shell photoelectrons and ab initio computations. Using a loop-like analysis scheme, we are able to deduce specific molecular coordinates with sensitivity even to the handedness of chiral molecules and the positions of individual atoms, e.g. , protons. more...

We report a joint experimental and theoretical study of the differential photoelectron circular dichroism (PECD) in inner-shell photoionization of uniaxially oriented trifluoromethyloxirane. By adjusting the photon energy of the circularly polarized synchrotron radiation, we address 1s-photoionization of the oxygen, different carbon, and all fluorine atoms. The photon energies were chosen such that in all cases electrons with a similar kinetic energy of about 11 eV are emitted. Employing coincident detection of electrons and fragment ions, we concentrate on identical molecular fragmentation channels for all of the electron-emitter scenarios. Thereby, we systematically examine the influence of the emission site of the photoelectron wave on the differential PECD. We observe large differences in the PECD signals. The present experimental results are supported by corresponding relaxed-core Hartree-Fock calculations. more...

The photoelectric effect describes the ejection of an electron upon absorption of one or several photons. The kinetic energy of this electron is determined by the photon energy reduced by the binding energy of the electron and, if strong laser fields are involved, by the ponderomotive potential in addition. It has therefore been widely taken for granted that for atoms and molecules, the photoelectron energy does not depend on the electron's emission direction, but theoretical studies have questioned this since 1990. Here, we provide experimental evidence that the energies of photoelectrons emitted against the light propagation direction are shifted toward higher values, while those electrons that are emitted along the light propagation direction are shifted to lower values. We attribute the energy shift to a nondipole contribution to the ponderomotive potential that is due to the interaction of the moving electrons with the incident photons. more...

The influence of the magnetic component of the driving electromagnetic field is often neglected when investigating light-matter interaction. We show that the magnetic component of the light field plays an important role in nonsequential double ionization, which serves as a powerful tool to investigate electron correlation. We investigate the magnetic-field effects in double ionization of xenon atoms driven by near-infrared ultrashort femtosecond laser pulses and find that the mean forward shift of the electron momentum distribution in light-propagation direction agrees well with the classical prediction, where no under-barrier or recollisional nondipole enhancement is observed. By extending classical trajectory Monte Carlo simulations beyond the dipole approximation, we reveal that double ionization proceeds via recollision-induced doubly excited states, followed by subsequent sequential over-barrier field ionization of the two electrons. In agreement with this model, the binding energies do not lead to an additional nondipole forward shift of the electrons. Our findings provide a new method to study electron correlation by exploiting the effect of the magnetic component of the electromagnetic field. more...

We experimentally and theoretically investigate the influence of the magnetic component of an electromagnetic field on high-order above-threshold ionization of xenon atoms driven by ultrashort femtosecond laser pulses. The nondipole shift of the electron momentum distribution along the light-propagation direction for high energy electrons beyond the 2U_{p} classical cutoff is found to be vastly different from that below this cutoff, where U_{p} is the ponderomotive potential of the driving laser field. A local minimum structure in the momentum dependence of the nondipole shift above the cutoff is identified for the first time. With the help of classical and quantum-orbit analysis, we show that large-angle rescattering of the electrons strongly alters the partitioning of the photon momentum between electron and ion. The sensitivity of the observed nondipole shift to the electronic structure of the target atom is confirmed by three-dimensional time-dependent Schrödinger equation simulations for different model potentials. Our work paves the way toward understanding the physics of extreme light-matter interactions at long wavelengths and high electron kinetic energies. more...

We present experimental data on the nonadiabatic strong field ionization of atomic hydrogen using elliptically polarized femtosecond laser pulses at a central wavelength of 390 nm. Our measured results are in very good agreement with a numerical solution of the time-dependent Schrödinger equation (TDSE). Experiment and TDSE show four above-threshold ionization peaks in the electron's energy spectrum. The most probable emission angle (also known as "attoclock offset angle" or "streaking angle") is found to increase with energy, a trend that is opposite to standard predictions based on Coulomb interaction with the ion. We show that this increase of deflection angle can be explained by a model that includes nonadiabatic corrections of the initial momentum distribution at the tunnel exit and nonadiabatic corrections of the tunnel exit position itself. more...

How long does it take to emit an electron from an atom? This question has intrigued scientists for decades. As such emission times are in the attosecond regime, the advent of attosecond metrology using ultrashort and intense lasers has re-triggered strong interest on the topic from an experimental standpoint. Here, we present an approach to measure such emission delays, which does not require attosecond light pulses, and works without the presence of superimposed infrared laser fields. We instead extract the emission delay from the interference pattern generated as the emitted photoelectron is diffracted by the parent ion's potential. Targeting core electrons in CO, we measured a 2d map of photoelectron emission delays in the molecular frame over a wide range of electron energies. The emission times depend drastically on the photoelectrons' emission directions in the molecular frame and exhibit characteristic changes along the shape resonance of the molecule., (© 2021. The Author(s).) more...

We report on a joint experimental and theoretical study of photoelectron circular dichroism (PECD) in methyloxirane. By detecting O 1s photoelectrons in coincidence with fragment ions, we deduce the molecule's orientation and photoelectron emission direction in the laboratory frame. Thereby, we retrieve a fourfold differential PECD clearly beyond 50%. This strong chiral asymmetry is reproduced by ab initio electronic structure calculations. Providing such a pronounced contrast makes PECD of fixed-in-space chiral molecules an even more sensitive tool for chiral recognition in the gas phase. more...

We investigate the differential ionization probability of chiral molecules in the strong-field regime as a function of the helicity of the incident light. To this end, we analyze the fourfold ionization of bromochlorofluoromethane (CHBrClF) with subsequent fragmentation into four charged fragments and different dissociation channels of the singly ionized methyloxirane. By resolving for the molecular orientation, we show that the photoion circular dichroism signal strength is increased by 2 orders of magnitude. more...

Strong-field ionization of atoms by circularly polarized femtosecond laser pulses produces a donut-shaped electron momentum distribution. Within the dipole approximation this distribution is symmetric with respect to the polarization plane. The magnetic component of the light field is known to shift this distribution forward. Here, we show that this magnetic nondipole effect is not the only nondipole effect in strong-field ionization. We find that an electric nondipole effect arises that is due to the position dependence of the electric field and which can be understood in analogy to the Doppler effect. This electric nondipole effect manifests as an increase of the radius of the donut-shaped photoelectron momentum distribution for forward-directed momenta and as a decrease of this radius for backwards-directed electrons. We present experimental data showing this fingerprint of the electric nondipole effect and compare our findings with a classical model and quantum calculations. more...

Photoionization is one of the fundamental light-matter interaction processes in which the absorption of a photon launches the escape of an electron. The time scale of this process poses many open questions. Experiments have found time delays in the attosecond (10 -18 seconds) domain between electron ejection from different orbitals, from different electronic bands, or in different directions. Here, we demonstrate that, across a molecular orbital, the electron is not launched at the same time. Rather, the birth time depends on the travel time of the photon across the molecule, which is 247 zeptoseconds (1 zeptosecond = 10 -21 seconds) for the average bond length of molecular hydrogen. Using an electron interferometric technique, we resolve this birth time delay between electron emission from the two centers of the hydrogen molecule., (Copyright © 2020 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.) more...

We report on a multiparticle coincidence experiment performed at the European X-ray Free-Electron Laser at the Small Quantum Systems instrument using a COLTRIMS reaction microscope. By measuring two ions and two electrons in coincidence, we investigate double core-hole generation in O_{2} molecules in the gas phase. Single-site and two-site double core holes have been identified and their molecular-frame electron angular distributions have been obtained for a breakup of the oxygen molecule into two doubly charged ions. The measured distributions are compared to results of calculations performed within the frozen- and relaxed-core Hartree-Fock approximations. more...

The investigation of the photoelectron circular dichroism (PECD) in the strong field regime (800 nm, 6.9 × 10 13 W/cm 2 ) on methyloxirane (MOX) reveals a flip of the sign of PECD between different fragmentation channels. This finding is of great importance for future experiments and applications in chemistry or pharmacy using PECD in the strong field regime as analysis method. We suggest that the observed sign change of PECD is not caused by ionization from different orbitals but by effectively selecting differently oriented nonisotropic subsamples of molecules via the fragmentation channel. more...

Chirality is omnipresent in living nature. On the single molecule level, the response of a chiral species to a chiral probe depends on their respective handedness. A prominent example is the difference in the interaction of a chiral molecule with left or right circularly polarized light. In the present study, we show by Coulomb explosion imaging that circularly polarized light can also induce a chiral fragmentation of a planar and thus achiral molecule. The observed enantiomer strongly depends on the orientation of the molecule with respect to the light propagation direction and the helicity of the ionizing light. This finding might trigger new approaches to improve laser-driven enantioselective chemical synthesis. more...

We suggest that low-energy electrons, released by resonant decay processes, experience substantial scattering on the electron density of excited electrons, which remain a spectator during the decay. As a result, the angular emission distribution is altered significantly. This effect is expected to be a common feature of low-energy secondary electron emission. In this Letter, we exemplify our idea by examining the spectator resonant interatomic Coulombic decay of Ne dimers. Our theoretical predictions are confirmed by a corresponding coincidence experiment. more...

We report on a kinematically complete measurement of double ionization of helium by a single 1100 eV circularly polarized photon. By exploiting dipole selection rules in the two-electron continuum state, we observed the angular emission pattern of electrons originating from a pure quadrupole transition. Our fully differential experimental data and companion ab initio nonperturbative theory show the separation of dipole and quadrupole contributions to photo-double-ionization and provide new insight into the nature of the quasifree mechanism. more...

We report on the nonadiabatic offset of the initial electron momentum distribution in the plane of polarization upon single ionization of argon by strong field tunneling and show how to experimentally control the degree of nonadiabaticity. Two-color counter- and corotating fields (390 and 780 nm) are compared to show that the nonadiabatic offset strongly depends on the temporal evolution of the laser electric field. We introduce a simple method for the direct access to the nonadiabatic offset using two-color counter- and corotating fields. Further, for a single-color circularly polarized field at 780 nm, we show that the radius of the experimentally observed donutlike distribution increases for increasing momentum in the light propagation direction. Our observed initial momentum offsets are well reproduced by the strong-field approximation. A mechanistic picture is introduced that links the measured nonadiabatic offset to the magnetic quantum number of virtually populated intermediate states. more...

We demonstrate a clear similarity between attoclock offset angles and Rutherford scattering angles taking the Keldysh tunneling width as the impact parameter and the vector potential of the driving pulse as the asymptotic velocity. This simple model is tested against the solution of the time-dependent Schrödinger equation using hydrogenic and screened (Yukawa) potentials of equal binding energy. We observe a smooth transition from a hydrogenic to "hard-zero" intensity dependence of the offset angle with variation of the Yukawa screening parameter. Additionally, we make a comparison with the attoclock offset angles for various noble gases obtained with the classical-trajectory Monte Carlo method. In all cases we find a close correspondence between the model predictions and numerical calculations. This suggests a largely Coulombic origin of the attoclock offset angle and casts further doubt on its interpretation in terms of a finite tunneling time. more...

We report on a direct method to measure the interatomic potential energy curve of diatomic systems. A cold target recoil ion momentum spectroscopy reaction microscope was used to measure the squares of the vibrational wave functions of H_{2}, He_{2}, Ne_{2}, and Ar_{2}. The Schrödinger equation relates the curvature of the wave function to the potential V(R) and therefore offers a simple but elegant way to extract the shape of the potential. more...

We examine correlated electron and doubly charged ion momentum spectra from strong field double ionization of neon employing intense elliptically polarized laser pulses. An ellipticity-dependent asymmetry of correlated electron and ion momentum distributions has been observed. Using a 3D semiclassical model, we demonstrate that our observations reflect the subcycle dynamics of the recollision process. Our Letter reveals a general physical picture for recollision impact double ionization with elliptical polarization and demonstrates the possibility of ultrafast control of the recollision dynamics. more...

The spin polarization of electrons from multiphoton ionization of Xe by 395 nm circularly polarized laser pulses at 6×10^{13}  W/cm^{2} has been measured. At this photon energy of 3.14 eV the above-threshold ionization peaks connected to Xe^{+} ions in the ground state (J=3/2, ionization potential I_{p}=12.1  eV) and the first excited state (J=1/2, I_{p}=13.4  eV) are clearly separated in the electron energy distribution. These two combs of above-threshold ionization peaks show opposite spin polarizations. The magnitude of the spin polarization is a factor of 2 higher for the J=1/2 than for the J=3/2 final ionic state. In turn, the data show that the ionization probability is strongly dependent on the sign of the magnetic quantum number. more...

Classical monoaminergic antidepressants show several disadvantages, such as protracted onset of therapeutic action. Conversely, the fast and sustained antidepressant effect of the N -methyl-d-aspartate receptor (NMDAR) antagonist ketamine raises vast interest in understanding the role of the glutamate system in mood disorders. Indeed, numerous data support the existence of glutamatergic dysfunction in major depressive disorder (MDD). Drawback to this short-latency therapy is its side effect profile, especially the psychotomimetic action, which seriously hampers the common and widespread clinical use of ketamine. Therefore, there is a substantial need for alternative glutamatergic antidepressants with milder side effects. In this article, we review evidence that implicates NMDARs in the prospective treatment of MDD with focus on rapastinel (formerly known as GLYX-13), a novel synthetic NMDAR modulator with fast antidepressant effect, which acts by enhancing NMDAR function as opposed to blocking it. We summarize and discuss current clinical and animal studies regarding the therapeutic potential of rapastinel not only in MDD but also in other psychiatric disorders, such as obsessive-compulsive disorder and posttraumatic stress disorder. Additionally, we discuss current data concerning the molecular mechanisms underlying the antidepressant effect of rapastinel, highlighting common aspects as well as differences to ketamine. In 2016, rapastinel received the Breakthrough Therapy designation for the treatment of MDD from the US Food and Drug Administration, representing one of the most promising alternative antidepressants under current investigation., Competing Interests: Disclosure The authors report no conflicts of interest in this work. more...

We report on nonsequential double ionization of Ar by a laser pulse consisting of two counterrotating circularly polarized fields (390 and 780 nm). The double-ionization probability depends strongly on the relative intensity of the two fields and shows a kneelike structure as a function of intensity. We conclude that double ionization is driven by a beam of nearly monoenergetic recolliding electrons, which can be controlled in intensity and energy by the field parameters. The electron momentum distributions show the recolliding electron as well as a second electron which escapes from an intermediate excited state of Ar^{+}. more...

The ground state of quantum systems is characterized by zero-point motion. This motion, in the form of vacuum fluctuations, is generally considered to be an elusive phenomenon that manifests itself only indirectly. Here, we report direct detection of the vacuum fluctuations of electromagnetic radiation in free space. The ground-state electric-field variance is inversely proportional to the four-dimensional space-time volume, which we sampled electro-optically with tightly focused laser pulses lasting a few femtoseconds. Subcycle temporal readout and nonlinear coupling far from resonance provide signals from purely virtual photons without amplification. Our findings enable an extreme time-domain approach to quantum physics, with nondestructive access to the quantum state of light. Operating at multiterahertz frequencies, such techniques might also allow time-resolved studies of intrinsic fluctuations of elementary excitations in condensed matter., (Copyright © 2015, American Association for the Advancement of Science.) more...

Folate deficiency has been linked to neurodegenerative and stress-related diseases such as stroke, dementia and depression. The role of the neurotrophins nerve growth factor (NGF) and neurotrophin-3 (NT-3) in stress-related disorders and neurodegeneration has garnered increasing attention in recent years. Uracil misincorporation is involved in the neuropsychiatric dysfunction induced by experimental folate deprivation. However, the effects of folate deficiency on the expression of NGF and NT-3 in brain tissue have not yet been investigated. In a 2×2 design, aged mice lacking uracil-DNA N-glycosylase (Ung(-/-)) versus wild-type (Ung(+/+)) controls were subjected to a folate-deficient diet versus a regular diet for three months. Independent of genotype, folate deficiency led to decreased NGF protein levels in the frontal cortex and amygdala. In the hippocampus, NGF levels were increased in UNG(-/-) mice on the normal diet, but not under folate deficiency, while in UNG(+/+) mice, folate deprivation did not affect hippocampal NGF content. NT-3 protein concentrations were neither affected by genotype nor by folate deficiency. Altogether, the results of our study show that folate deficiency affects NGF levels in the frontal cortex, amygdala and hippocampus. The decrease in NGF content in the hippocampus in response to folate deficiency in Ung(-/-) mice may contribute to their phenotype of enhanced anxiety and despair-like behavior as well as to selective hippocampal neurodegeneration., (Copyright © 2013 IBRO. Published by Elsevier Ltd. All rights reserved.) more...