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Purpose: To improve the outcome of fetuses with gastrochisis several studies evaluated prenatal predictors. But there are different guidelines established and therefore the prenatal care is not standardized. With our study we wanted to evaluate the outcome of fetuses with gastroschisis after modification of prenatal management strategies at the Department of Obstetrics and Gynecology of the University Hospital Münster.Methods: In this explorative retrospective study of 39 fetuses with gastroschisis, we compare the clinical outcome between two management groups. In the first group (group 1, n = 14) prenatal indication for delivery was confirmed by a subjective evaluation of the small bowel diameter and the wall thickness without established cut-off values for these parameters. In the second group (group 2, n = 25) certain limits for the small bowel diameter (25 mm) and the wall thickness (2.5 mm) were used for fetal surveillance.Results: Noticeable differences between the two groups regarding birth weight, weight centile, arterial pH, small bowel diameter, wall thickness, adverse bowel condition and re-operations could not be observed. In group 2, delivery was earlier (p = 0.011), and a lower rate of prenatal complications was observed (p = 0.016).Conclusion: To avoid adverse prenatal complications we recommend the observation of fetuses with gastroschisis by sonographic monitoring of the small bowel diameter and the wall thickness. [ABSTRACT FROM AUTHOR]

In 1937, W. Jost speculated about the possible positions and dynamics of the silver ions in the high-temperature phase of silver iodide, α-AgI, that one would encounter, if it could be cooled far below its regular 147 °C α–β phase transition. Would a (continuous) ‘liquid–solid transition’ occur in the silver sublattice and would the ‘liquid-like’ dynamics of the mobile silver ions change into a ‘solid-like’ hopping motion? We are now, for the first time, able to answer Jost's questions, both of them in the affirmative. In our samples, globules of crystalline α-AgI were contained in a powdered glass of composition 0.78 AgI · 0.165 Ag 2 O · 0.055 B 2 O 3 , prepared from the melt by roller quenching and subsequent grinding in liquid nitrogen. In a Rietveld refinement of X-ray diffraction data, taken at 100 K, the silver ions were found to be localized within the tetrahedral voids provided by the α-AgI anion structure. The change from the high-temperature ‘liquid-like’ dynamics of the silver ions into a ‘solid-like’ hopping motion could be verified by considering spectra of the ionic conductivity. With decreasing temperature, the spectra do, indeed, develop the characteristic frequency dependence which is a hallmark of ionic hopping. [ABSTRACT FROM AUTHOR]

Abstract: A pronounced nearly constant loss (NCL) contribution to the frequency-dependent conductivity has been detected in the low-temperature γ-phase of the archetypal crystalline fast ion conductor, rubidium silver iodide. At 113 K, the conductivity spectrum, σ(ν), of γ-RbAg4I5 has been measured in a wide frequency range extending up to more than 100 GHz. In contrast to the phases α and β, the spectrum cannot be interpreted as a superposition of a high-frequency vibrational part plus a low-frequency dispersive component that reflects the ionic hopping dynamics responsible for macroscopic ionic transport. Rather, an additional NCL component is identified featuring a roughly linear σ(ν)∝ ν behavior within about two decades of frequency. This component is found to merge into saturation at high frequencies and into a σ(ν)∝ ν2 behavior at low frequencies. It is well reproduced in terms of a model describing highly correlated, strictly localized displacive movements of interacting ions. The model is based on the concept of mismatch and relaxation (CMR). [Copyright &y& Elsevier]

Frequency-dependent conductivities and permittivities of ion-conducting materials reflect the dynamics of the mobile ions. Experimentally, the development of the ion dynamics with time can thus be monitored from less than a picosecond up to minutes and hours. In this paper, we show that the characteristics of frequency-dependent conductivities and permittivities of solid ion conductors are well reproduced within the framework of the MIGRATION concept. The meaning of the acronym is MIsmatch Generated Relaxation for the Accommodation and Transport of IONs. In this model treatment, a simple set of rules is introduced in order to describe the essence of the ion dynamics in terms of a physical picture of the most relevant elementary processes. The rules are expressed in terms of three coupled rate equations, which form the basis for deriving frequency-dependent model conductivities and permittivities as well as mean square displacements. [Copyright &y& Elsevier]

The concept of mismatch and relaxation (CMR) provides a model description for the dynamics of the hopping motion of ions in ion-conducting materials. The following applications are discussed. (i) In the crystalline fast ion conductor RbAg4I5 the CMR is employed to analyse the gradual transition from random to nonrandom hopping that is found to occur below 298 K. (ii) When used to describe the ion dynamics in fragile supercooled melts, the CMR yields a new equation for the temperature dependence of the dc conductivity. (iii) In interacting dipole systems, the nearly-constant-loss (NCL) behaviour is reproduced by the CMR. (iv) After introduction of a structure-sensitive parameter, the CMR is able to fit experimental conductivity spectra that display significant differences in shape. [Copyright &y& Elsevier]

Abstract: We present the three coupled rate equations of the mismatch generated relaxation for the accommodation and transport of ions (MIGRATION) concept that describe the ion dynamics in, for example, ion-conducting glasses and simultaneously yield scaled conductivity and permittivity spectra. Here, model spectra are compared with the experimental spectra of xNa2O·(1-x)GeO2 glasses for x=0.0513, 0.0902, 0.213. This allows us to estimate the long-time limit of the localized rms displacement, , which may be roughly interpreted as the average size of the ion cage before the dynamics become diffusive. For the three compositions considered, we obtain an approximate x−1/3 dependence of this quantity, which implies that the ion dynamics are largely governed by the Coulomb interactions between the mobile ions. [Copyright &y& Elsevier]

Animal TMS models are especially useful for studying the cellular and molecular effects related to the lasting effects achieved with prolonged stimulation of a particular pattern (rTMS). In translational terms, it is exceptionally challenging to realize stimulation conditions resembling those supposed to occur in the human brain. Due to the very different ratio of coil-to-brain sizes, a focal stimulation of small animal brains as can be achieved in humans using figure-of-eight coils is hardly realistic today. Attempts to develop small (e.g. rodent coils) are confronted with reduced field power or limited number of high-frequency train pulses due to heating problems. Nevertheless, animal TMS models will be helpful in terms of studying relationships between stimulation-induced changes in neuronal activity and plasticity and changes in behavioral phenotypes. Differences in rTMS effects found in Parkinson patients compared to healthy controls which appear to be related to disturbed synaptic plasticity could be replicated in a rat Parkinson disease model ( Hsieh et al., 2015 ) and beneficial stimulation effects related to modulation of striatal dopamine content have been reported ( Ghiglieri et al., 2012 ). Principally, global brain stimulation using rTMS appears adequate if studying neuromodulatory effects not confined to a particular system as is found with changes in extracellular levels of dopamine or glutamate, brain-derived neurotrophic factor (BDNF), pro- or anti-inflammatory mediators and changes in the excitatory-inhibitory balance ( Suppa et al., 2016 ). Nonfocal cortical and/or subcortical stimulation should be suitable to also answer the question if distinct types of neurons (including their genesis and developmental state) or their compartments are more sensitive to a particular stimulation protocol than others if analyzing neuronal activity and plasticity markers. Even if those changes have been achieved with limited focal stimulation in vivo, matched in vitro studies on isolated neuronal systems allow estimating the relevance of focal stimulation as recently demonstrated for the entorhino-hippocampal pathway in mice ( Lenz et al., 2016 ). Focal electric stimulation applied in a way to either mimic the timing of spatially distant evoked activity – as in case of interhemispheric stimulation ( Barry et al., 2014 )-, or to mimic the electric field distribution likely achieved with an imaginary focal coil could further help to evaluate the differences between focal and global stimulation. However, it has to be kept in mind that magnetic fields induced a different electric field distribution within the tissue as can be achieved with contact electrodes, both with regard to spatial current density and also with regard to extra- and intracellular induction of electric field gradients. In this respect, animal studies demonstrating neuronal effects with patterned magnetic stimulation of rather low field strength (10–100 mT) are of further interest, indicating modulation of molecular processes like intracellular calcium release and gene expression even in the absence of detectable electric responses ( Grehl et al., 2015 ). Even if animal models cannot imitate TMS of human cortex in a one-to-one fashion, they definitely offer new ways to investigate how magnetically induced electric field can interact with neuronal processes and which factors determine a variable result of stimulation. [ABSTRACT FROM AUTHOR]

Neural functioning and plasticity can be studied on different levels of organization and complexity ranging from the molecular and synaptic level to neural circuitry of whole brain networks. Across neuroscience different methods are being applied to better understand the role of various neurotransmitter systems in the evolution of perception and cognition. GABA is the main inhibitory neurotransmitter in the adult mammalian brain and, depending on the brain region, up to 25% of the total number of cortical neurons are GABAergic interneurons. At the one end of the spectrum, GABAergic neurons have been accurately described with regard to cell morphological, molecular, and electrophysiological properties; at the other end researchers try to link GABA concentrations in specific brain regions to human behavior using magnetic resonance spectroscopy. One of the main challenges of modern neuroscience currently is to integrate knowledge from highly specialized subfields at distinct biological scales into a coherent picture that bridges the gap between molecules and behavior. In the current review, recent findings from different fields of GABA research are summarized delineating a potential strategy to develop a more holistic picture of the function and role of GABA. [ABSTRACT FROM AUTHOR]

Introduction: Human cortical excitability can be modified by repetitive transcranial magnetic stimulation (rTMS) but the factors that determine the direction of change remain still elusive. Classical forms of synaptic plasticity and metaplastic processes like homeostatic synaptic scaling and priming-dependent synaptic plasticity are possible mechanistic scenarios. Although the activity of excitatory neurons finally represents the degree of cortical activation, a multitude of inhibitory cortical systems governs about magnitude and pattern of cortical activity and the degree of plasticity allowed without loosing essential excitation-inhibition balance. It is thus likely that rTMS-induced changes in cortical excitability are associated with changes in cortical inhibition and that classes of interneurons differently contribute. Objectives: We established a rat model of rTMS enabling to study cellular effects of rTMS in more detail and with possible relation to behavioural changes. To focus on changes in inhibitory cortical activity, we studied the expression of certain activity markers which are specific to inhibitory neurons in general, like the two isoforms of the glutamic acid decarboxylase GAD65 and GAD67, or relate to a certain class of interneurons, like the expression of the calcium-binding proteins parvalbumin (PV), calbindin (CB) and calretinin (CR). Our recent studies focus on the temporal dynamics of these activity markers which is of particular interest in case of combining rTMS with other artificial or natural interventions or repeated rTMS. Materials and methods: Adult male Sprague–Dawley rats (n =42.15weeks old) were trained to tolerate the procedure of manual restrain and rTMS without signs of stress before receiving a single block (600 pulses) of either verum or sham intermittent theta-burst stimulation protocol (iTBS) at an intensity just subthreshold for evoking motor responses (MagStim rapid, 70mm figure-of-eight coil). Then, rat were deeply anesthetized and perfused at different intervals post-rTMS (10, 20, 40, 80, 160min) for immunohistochemical analysis of neuronal activity marker expression (GAD65/67, PV, CB for inhibitory neurons; c-Fos and zif268 mainly for excitatory neurons). Results: Three phases of changes in neuronal activity marker expression could be distinguished: an early phase (10–20min) of strongly increased c-Fos and GAD65 expression, a following phase (40–80min) of reduced GAD67, PV and CB expression and a late phase (>160min) of reduced c-Fos and GAD65 expression. Conclusion: Early increased levels of c-Fos and GAD65 indicate a strong co-activation of excitatory and inhibitory neurons due to iTBS. The delayed decrease in GAD67, PV and CB expression indicates a secondary depression of activity of inhibitory neurons without signs of increased excitatory activity (c-Fos, zif268). The late decrease in c-Fos and GAD65 finally indicates a matched reduction in the activity of both excitatory and inhibitory activities. Obviously, excitation-inhibition balance is never violated but the phases of changed synaptic (GAD65) and somatic (GAD67, PV, CB) inhibitory neuron activity to not co-vary in time. This study has been supported by the Deutsche Forschungsgemeinschaft, DFG (FU 256/3-2, SFB 874, TP A4). [Copyright &y& Elsevier]

The article discusses the Barmer study which aims to examine the impact of standard injection-site warming on prandial insulin dose and frequency of hypoglycemia in obese patients with diabetes mellitus. It mentions that 145 patient were treated with insulin glargine, an analog therapy under the observation parameters includes HbA1c, insulin dose and body weight. Also mentions that by using the injection-site warming device results the decline in the hypoglycemic events.

Abstract: We present, for the first time, broadband conductivity spectra of a salt-in-polymer electrolyte, i.e., of 1 molal NaPF6 dissolved into a crosslinked PEO-PPO random copolymer. The experimental frequency range spans nearly 12 decades, extending up to the far infrared. The temperature range is from 303 K to 363 K. The conductivity spectra show a remarkably gradual onset of the dispersion, which is reminiscent of ion conducting glasses and crystalline ion conductors, where ions hop via well-defined sites. On the other hand, the DC conductivity of the polymer electrolyte shows a non-Arrhenius temperature dependence, thus resembling dynamically coupled systems such as supercooled melts. Any approach to understanding these seemingly contradictory features must include ion–ion interactions and, hence, go beyond models based on free volume theory. Such an approach is provided by the MIGRATION concept (MIsmatch Generated Relaxation for the Accommodation and Transport of IONs). In this treatment, the non-Arrhenius DC conductivity is described by an equation which yields, e.g., the elementary hopping rate and the shape of the conductivity spectra at higher frequencies. The entire conductivity spectra with the vibrational component suitably removed is a superposition of two components—one due to ionic displacements resulting in translational motion, the other due to localized movements causing a Nearly Constant Loss (NCL) type behaviour. [Copyright &y& Elsevier]

The ionic Hall effect has been measured in the crystalline fast ion conductor rubidium silver iodide, RbAg4I5, at temperatures from 373 K to 473 K. A novel variant of the alternating E/alternating B technique has been employed, with the alternating magnetic field supplied by a rotating permanent 1 T magnet. The value of the Hall mobility is found to be considerably smaller than reported earlier by T. Kaneda and E. Mizuki. It is now found to be identical with the drift mobility obtained under the assumption that all the silver ions in the solid electrolyte contribute to the conduction process. The same is known to hold in the archetypal fast ion conductor α-AgI. [Copyright &y& Elsevier]

Abstract: We present new insights into the Nearly Constant Loss (NCL) effect, which are based on a study of conductivity as a function of temperature and frequency in 0.3Na2O·0.7B2O3 and 0.5AgI·0.5AgPO3 glasses. In these systems, the ionic conductivity has been measured over a temperature range from 4K to 475K and in a frequency range from a few mHz to a few MHz. The conductivity spectra taken at various temperatures have then been mapped on to a representation of conductivity versus temperature (or inverse temperature) at fixed frequency. Indeed, such plots are often published in studies of the NCL effect. For a given system and a given frequency, an equivalent mapping is achieved by using suitable scaled model conductivity spectra derived from the MIGRATION concept. This enables us to identify, at fixed frequency, the temperature of transition from the ionic conductivity caused by the “ordinary” correlated hopping motion of the mobile ions (now known as the “first” universality) to the classical NCL behaviour (which Nowick termed “new” or “second” universality). We describe the details of our procedure and show that insights emerge with regard to both the high-frequency plateau of the conductivity component due to “ordinary” hopping and the NCL effect itself. [Copyright &y& Elsevier]

Questions Our previous studies showed that intermittent theta-burst stimulation (iTBS) applied via transcranial magnetic stimulation (TMS) to the rat brain strongly reduced the expression of the calcium-binding protein parvalbumin (PV) in fast-spiking inhibitory interneurons (FSI). This finding indicates that disinhibition and the associated increase in cortical excitability may be one way to open a window for plastic changes in the cortical network. The mechanisms leading to reduced PV expression are not known but are either related to a strong activation during iTBS or a subsequent reduction in glutamatergic excitation of FSI in a manner of Ltd. One well-described regulator of glutamate release at excitatory terminals is neuropeptide Y (NPY) which has been shown to be up-regulated after epileptic activity. Therefore, we tested if iTBS increases the expression of NPY in rat cortex, whether the reduced PV expression in FSI is associated with reduced activity of excitatory inputs and finally if intrathecal application of NPY prior to TMS can counteract the cortical iTBS effect. Methods In a first study, parallel changes in the cortical expression of PV and NPY in rats previously treated with one to five blocks of iTBS (600 pulses per block, intervals of 15 min) were analysed using immunohistochemistry. In a second study, we analysed the relationship between the level of PV expression of single FSI and the strength of glutamatergic input measured as the level of expression of the vesicular glutamate transporter type 1 (VGluT1) in cortical synapses terminating on FSI. Finally in a third study, rats received either 20 μ l NPY (24 nMol) or methylene blue as a control (MB) via intracranial injection to the left lateral ventricle (2 μ l/min) followed 60 min later by either verum or sham iTBS (3 blocks @ 15 min = 1800 pulses) to test if enhanced NPY level can influence the effect of iTBS on PV and vGluT1 expression. Results In a dose-dependent fashion, iTBS gradually decreased the number of PV+ neurons but also increased the level of NPY in the neuropil and the number of NPY+ neurons. Interneurons showing low PV expression had a significantly weaker labelling of glutamatergic cortical input (less vGluT1) than cells showing high PV level. NPY injected into the lateral ventricle of the left forebrain (no diffusion to the right hemisphere) prevented the reduction of PV+ cells (−40%) by iTBS in the left but not in the right hemisphere and further increased the number of PV+ cells. A slight increase in PV+ cells was also evident in sham stimulated animals when comparing NPY with MB injections. Conclusions As expected, iTBS increased the expression of NPY likely due to the strong and highly synchronous activation of cortical networks. Since strong excitation is especially harmful to FSI, the reduction in PV expression appears to signal a post-stimulation depression of excitatory inputs and subsequent hypoactivity of these interneurons. The finding that NPY prevents the strong reduction in PV expression indicates that it is able to prevent over-excitation of FSI. This study has been supported a grant of the Federal Ministry of Education and Research (BMBF): GCBS-WP1_Bochum ( 01EE1403B ) to K. Funke. [ABSTRACT FROM AUTHOR]

Question Gestational infection is a risk factor for psychiatric disorders. Accordingly, preclinical models of maternal immune activation (MIA) have been developed to study effects of gestational infection on neural and behavioral dysfunction in the offspring. Considering that early pre-symptomatic stages of schizophrenia may affect hippocampal circuits, we here established a hippocampal ‘organotypic in vitro MIA model’ based on the well-established polyinosinic-polycytidylic acid [Poly(I:C)] model of schizophrenia. We studied alterations in synaptic neurotransmission and tested whether repetitive magnetic stimulation (rMS) influences alterations in synaptic excitation/inhibition-balance in this model. Methods Entorhino-hippocampal slice cultures were prepared from litters of Poly(I:C) or vehicle-only injected pregnant dams. The effects of 10 Hz rMS on MIA associated alterations in synaptic properties were assessed in CA1 pyramidal neurons using whole-cell patch clamp recordings. Results Our experiments disclose an increase in inhibitory synaptic strength, while excitatory synapses on CA1 neurons are not changed in slice cultures prepared from Poly(I:C) offspring. This difference is also observed in cultures prepared from cross-fostered animals, thus confirming that gestational infection triggers the synaptic phenotype. Since our recent work has demonstrated that 10 Hz rMS can shift synaptic excitation/inhibition-balance toward excitation, we employed this rMS protocol to test whether we can influence the synaptic phenotype in the Poly(I:C) group. Indeed, 10 Hz rMS reversed the increased inhibitory synaptic strength without affecting excitatory synapses in MIA slice cultures. Conclusion These results suggest that rMS may exert positive effects under pathological conditions by restoring physiological synaptic excitation/inhibition-balance. We propose that ‘organotypic in vitro MIA models’ may serve as preclinical drug and intervention screening assays to evaluate and learn more about rTMS-based treatment strategies in psychiatric diseases associated with gestational infection. (Supported by Federal Ministry of Education and Research, Germany (BMBF, GCBS-WP1: 01EE1403B).). [ABSTRACT FROM AUTHOR]

Question The cellular and molecular mechanisms of rTMS-induced neural plasticity remain not well understood. Recent experimental evidence obtained in mouse brain slice cultures disclosed that 10 Hz repetitive magnetic stimulation (rMS) induces long-term potentiation (LTP) of excitatory neurotransmission. These studies support the notion that rTMS acts through the induction of ‘LTP-like’ plasticity. Here, we tested whether rTMS increases cortical excitability by mediating long-term depression (LTD) of inhibitory neurotransmission. Methods Immunohistochemistry, fluorescence recovery after photobleaching, GABA-uncaging experiments and paired whole-cell patch clamp recordings were used in entorhino-hippocampal slice cultures to study the effects of 10 Hz rMS on structural and functional properties of inhibitory synapses of CA1 pyramidal neurons. Results We report that 10 Hz rMS reduces dendritic but not somatic GABAergic neurotransmission onto CA1 pyramidal neurons. These functional changes are accompanied by structural remodeling of inhibitory postsynapses and depend on the activation of voltage gated sodium channels, L-type voltage gated calcium channels, NMDA-receptors, and calcineurin protein phosphatases. Consistent with these findings, a reduction in gephyrin cluster sizes and numbers is detected in CA1 stratum radiatum 2 h after 10 Hz rTMS of anaesthetized mice. Conclusion rMS appears to be a potent tool to induce Ca 2+ -dependent structural and functional changes of both excitatory and inhibitory synapses. We propose that 10 Hz rTMS may shift excitation/inhibition-balance in neuronal networks by inducing LTP of excitatory and LTD of inhibitory neurotransmission. (Supported by DFG and Federal Ministry of Education and Research, Germany; GCBS-WP1.) [ABSTRACT FROM AUTHOR]

Questions High-frequency transcranial magnetic stimulation with theta-burst stimulation (TBS) induces strong and highly synchronous cortical network activity principally able to trigger epileptiform activity or to cause over-excitation of distinct neurons. Our previous studies showed that intermittent TBS (iTBS) strongly reduces the expression of the calcium-binding protein parvalbumin (PV) in fast-spiking inhibitory interneurons (FSI). Since PV is expressed in an activity-dependent manner, strong activation of these neurons during iTBS might have triggered mechanisms to prevent permanent over-excitation. One well-described process is the reduction of glutamate release from excitatory terminals targeting FSI via the action of neuropeptide Y (NPY). Therefore, we first tested if iTBS increases the expression of NPY in rat cortex and second, if application of NPY to the lateral ventricle can counteract the cortical iTBS effect of reducing PV expression. Methods In the first study, frontal sections of rat brains previously treated with one to five blocks of iTBS (600 pulses per block, intervals of 15 min) were immunostained for NPY and PV. In the second study, rats received either 20 μ l NPY (24 nMol) or methylene blue as a control (MB) via intracranial injection to the left lateral ventricle (2 μ l/min) followed 60 min later by either verum or sham iTBS (3 blocks @ 15 min = 1800 pulses). Further 60 min later rats were perfused for PV immunostaining of their brains. Results iTBS gradually increased the number of NPY+ neurons in a dose-dependent fashion from about 60 cells/mm 2 to about 130 cells/mm 2 after five iTBS blocks. The same stimulation protocol was previously found to decrease the number of PV+ neurons by about 40% after five iTBS blocks (Volz et al., Brain Stimulation 2013). NPY injected into the lateral ventricle of the left forebrain (no diffusion to the right hemisphere) prevented the reduction of PV+ cells (−40%) by iTBS in the left but not in the right hemisphere and further increased the number of PV+ cells. A slight increase in PV+ cells was also evident in sham stimulated animals when comparing NPY with MB injections. Conclusions As expected, iTBS increased the expression of NPY likely due to the strong and highly synchronous activation of cortical networks. Since strong excitation is especially harmful to FSI, the reduction in PV expression indicates a post-stimulation depression of excitatory inputs and subsequent hypoactivity of these interneurons. The finding that NPY prevents the strong reduction in PV expression indicates that it is able to prevent over-excitation of FSI. This study has been supported by grants of the Deutsche Forschungsgemeinschaft (DFG): SFB 874 TP A4 and the Federal Ministry of Education and Research (BMBF): GCBS-WP1_Bochum (01EE1403B) to K. Funke. [ABSTRACT FROM AUTHOR]

Introduction: Theta Burst stimulation (TBS) applied via transcranial magnetic stimulation (TMS) is an effective tool to modulate human neocortical excitability (Huang et al., 2005). Repeated application of the same TBS protocol or variation of the number of stimuli has been shown to alter the strength and direction of changes in cortical excitability compared to the standard TBS protocols (Gentner et al., 2008; Gamboa et al., 2010). TBS applied to rat cortex affected the expression of activity-dependent proteins related to the cortical inhibitory systems, suggesting altered cortical inhibition contributing to the TBS after-effects (Benali et al., 2011; Funke and Benali, 2011). Objectives: Our aim was to investigate the impact of varying numbers of TBS-stimuli applied as multiple blocks of intermittend TBS (iTBS) or continuous TBS (cTBS) on cortical protein expression in the rat, to further our insights in physiological mechanisms underlying TBS-induced changes in cortical excitability. Materials and methods: Nine groups of anesthetized rats (male Sprague Dawley, 400–600g) received TMS. Eight groups received a different number of iTBS/cTBS-blocks summing up to either 600, 1200, 1800, or 2400 stimuli, applied with breaks of 15min between blocks of 600 stimuli. Sham stimulation (coil more distant to the head) was applied to a control group. Rats were sacrificed for immunohistochemical analysis or western blotting focussing on frontal, motor, sensory and visual cortex. Results: In general, quite similar effects for iTBS and cTBS were observed. The expression of the 65-kDa isoform of glutamic acid decarboxylase (GAD65) increased, while that of the 67-kDa isoform (GAD67) and that of the calcium-binding proteins Parvalbumin (PV) and Calbindin (CB) progressively decreased. Also the expression of the immediate early gene c-Fos decreased with an increasing number of blocks. A more detailed analysis, however, revealed that the sensitivity of distinct proteins to stimulation varied with the number of stimuli and type of stimulation. Conclusion: Our findings show that both iTBS and cTBS affect the activity of inhibitory interneurons and indicate that repeated TBS elicits no simple accumulative dose-dependent effect for all activity-markers but distinct profiles with threshold characteristics and a waxing-and-waning effect especially for two markers of inhibitory activity, CB and GAD67. Thus, our data do not suggest fundamentally different modulation of the cortical inhibitory systems by iTBS and cTBS. Subtle differences in stimulation after-effects on different neuronal subsystems might contribute to the opposite impact on cortical excitability following iTBS and cTBS and the switching sign of effect with repeated stimulation. [Copyright &y& Elsevier]