Fluctuating Inhibitory Inputs Promote Reliable Spiking at Theta Frequencies in Hippocampal Interneurons

Theta-frequency (4–12 Hz) rhythms in the hippocampus play important roles in learning and memory. CA1 interneurons located at the stratum lacunosum-moleculare and radiatum junction (LM/RAD) are thought to contribute to hippocampal theta population activities by rhythmically pacing pyramidal cells with inhibitory postsynaptic potentials. This implies that LM/RAD cells need to fire reliably at theta frequencies in vivo. To determine whether this could occur, we use biophysically based LM/RAD model cells and apply different cholinergic and synaptic inputs to simulate in vivo-like network environments. We assess spike reliabilities and spiking frequencies, identifying biophysical properties and network conditions that best promote reliable theta spiking. We find that synaptic background activities that feature large inhibitory, but not excitatory, fluctuations are essential. This suggests that strong inhibitory input to these cells is vital for them to be able to contribute to population theta activities. Furthermore, we find that Type I-like oscillator models produced by augmented persistent sodium currents (INaP) or diminished A-type potassium currents (IA) enhance reliable spiking at lower theta frequencies. These Type I-like models are also the most responsive to large inhibitory fluctuations and can fire more reliably under such conditions. In previous work, we showed that INaP and IA are largely responsible for establishing LM/RAD cells’ subthreshold activities. Taken together with this study, we see that while both these currents are important for subthreshold theta fluctuations and reliable theta spiking, they contribute in different ways – INaP to reliable theta spiking and subthreshold activity generation, and IA to subthreshold activities at theta frequencies. This suggests that linking subthreshold and suprathreshold activities should be done with consideration of both in vivo contexts and biophysical specifics

Modeling Planetary Opacities With Hitran And Hapi: Test Case Of Ammonia Microwave Absorption Spectra Under Jovian Condition

The HITRAN (high-resolution transmission molecular spectroscopic database) is an international standard for reference molecular spectroscopy, particularly in simulating planetary and terrestrial atmospheric spectra [1]. HITRAN recently added new broadening parameters that are relevant to planetary atmospheres for many chemical species in the database. For NH$_3$, new broadening parameters include H$_2$, He, CO$_2$ [2] and H$_2$O [3]. These additional broadening parameters for NH$_3$ allowed for validations of HITRAN data with the HITRAN Application Programming Interface (HAPI) [4] against the NH$_3$ opacity models and laboratory data utilized by the Juno Mission. The Juno spacecraft carries with it a microwave radiometer which probes the atmospheric composition of Jupiter in the microwave range (0.02-0.73 cm$^{-1}$) [5,6]. At these frequencies, Jupiter’s atmospheric spectra is dominated by the inversion of NH$_3$ and is broadened by H$_2$, He, and H$_2$O. This work required three new line shapes to be incorporated into HAPI in order to accurately compare to available laboratory data and standard NH$_3$ opacity models (the Ben-Reuven [7], Gross [8] and Van Vleck and Weisskopf [9] line shapes). The results of this work demonstrate that HAPI can be used with HITRAN data, to model NH$_3$ opacities under Jovian conditions in the microwave region. It also shows great promise to produce opacities for other species of interest to the planetary community.\newline \newline \noindent\scriptsize{\underline{References}}\newline [1] I. E. Gordon, et al. JQSRT, 203:3–69, 2017.\newline [2] J. S. Wilzewski, et al. JQSRT, 168:193–206, 2016.\newline [3] Y. Tan, et al. JGR (Atmospheres), 124(21): 11580–11594, 2019.\newline [4] R. V. Kochanov, et al. JQSRT, 177:15–30, 2016.\newline [5] M. A. Janssen, et al. Space Science Reviews, 213(1–4):139–185, 2017.\newline [6] S. J. Bolton, et al. Science, 356(6340):821–825, 2017.\newline [7] A. Ben-Reuven, Physical Review, 145:7–22, 1966.\newline [8] E. P. Gross, Physical Review, 97: 395–403, 1955.\newline [9] J. H. Van Vleck and V.F. Weisskopf, Review Modern Physics, 17:227–236, 1945

Referencing Sources of Molecular Spectroscopic Data in the Era of Data Science: Application to the HITRAN and AMBDAS Databases

The application described has been designed to create bibliographic entries in large databases with diverse sources automatically, which reduces both the frequency of mistakes and the workload for the administrators. This new system uniquely identifies each reference from its digital object identifier (DOI) and retrieves the corresponding bibliographic information from any of several online services, including the SAO/NASA Astrophysics Data Systems (ADS) and CrossRef APIs. Once parsed into a relational database, the software is able to produce bibliographies in any of several formats, including HTML and BibTeX, for use on websites or printed articles. The application is provided free-of-charge for general use by any scientific database. The power of this application is demonstrated when used to populate reference data for the HITRAN and AMBDAS databases as test cases. HITRAN contains data that is provided by researchers and collaborators throughout the spectroscopic community. These contributors are accredited for their contributions through the bibliography produced alongside the data returned by an online search in HITRAN. Prior to the work presented here, HITRAN and AMBDAS created these bibliographies manually, which is a tedious, time-consuming and error-prone process. The complete code for the new referencing system can be found at \url{https://github.com/hitranonline/refs}.Comment: 11 pages, 5 figures, already published online at https://doi.org/10.3390/atoms802001

Theory, models and biology

Theoretical ideas have a rich history in many areas of biology, and new theories and mathematical models have much to offer in the future

Dendritic distributions of l\u3csub\u3eh\u3c/sub\u3e channels in experimentally-derived multi-compartment models of oriens-lacunosum/moleculare (O-LM) hippocampal interneurons

The O-LM cell type mediates feedback inhibition onto hippocampal pyramidal cells and gates information flow in the CA1. Its functions depend on the presence of voltage-gated channels (VGCs), which affect its integrative properties and response to synaptic input. Given the challenges associated with determining densities and distributions of VGCs on interneuron dendrites, we take advantage of computational modeling to consider different possibilities. In this work, we focus on hyperpolarization-activated channels (h-channels) in O-LM cells. While h-channels are known to be present in O-LM cells, it is unknown whether they are present on their dendrites. In previous work, we used ensemble modeling techniques with experimental data to obtain insights into potentially important conductance balances. We found that the best O-LM models that included uniformly distributed h-channels in the dendrites could not fully capture the “sag” response. This led us to examine activation kinetics and non-uniform distributions of h-channels in the present work. In tuning our models, we found that different kinetics and non-uniform distributions could better reproduce experimental O-LM cell responses. In contrast to CA1 pyramidal cells where higher conductance densities of h-channels occur in more distal dendrites, decreasing conductance densities of h-channels away from the soma were observed in O-LM models. Via an illustrative scenario, we showed that having dendritic h-channels clearly speeds up back-propagating action potentials in O-LM cells, unlike when h-channels are present only in the soma. Although the present results were morphology-dependent, our work shows that it should be possible to determine the distributions and characteristics of O-LM cells with recordings and morphologies from the same cell. We hypothesize that h-channels are distributed in O-LM cell dendrites and endow them with particular synaptic integration properties that shape information flow in hippocampus

Mean field analysis gives accurate predictions of the behaviour of large networks of sparsely coupled and heterogeneous neurons

Large networks of integrate-and-fire (IF) model neurons are often used to simulate and study the behaviour of biologically realistic networks. However, to fully study the large network behaviour requires an exploration of large regions of a multidimensional parameter space. Such exploration is generally not feasible with large network models, due to the computational time required to simulate a network with biologically significant size. To circumvent these difficulties we use a mean-field approach, based on the work of [1]. We consider a sparsely coupled, excitatory network of 10,000 Izhikevich model neurons [2], with Destexhe-type synapses [3]. The cellular models were fit to hippocampal CA1 pyramidal neurons and have heterogeneous applied currents with a normal distribution. We derived a mean-field system for the network which consists of differential equations for the mean of the adaptation current and the synaptic conductance. As CA1 is an area that displays prominent theta oscillations [4], we used the mean-field system to study how the frequency of bursting depends on various model parameters. Figure 1A shows an example study. These studies were successful in guiding numerical simulations of the large network. When parameter values determined from the mean-field analysis are used in a large network simulation, bursting of the predicted frequency occurs

Dietary garlic and hip osteoarthritis: evidence of a protective effect and putative mechanism of action

Background Patterns of food intake and prevalent osteoarthritis of the hand, hip, and knee were studied using the twin design to limit the effect of confounding factors. Compounds found in associated food groups were further studied in vitro. Methods Cross-sectional study conducted in a large population-based volunteer cohort of twins. Food intake was evaluated using the Food Frequency Questionnaire; OA was determined using plain radiographs. Analyses were adjusted for age, BMI and physical activity. Subsequent in vitro studies examined the effects of allium-derived compounds on the expression of matrix-degrading proteases in SW1353 chondrosarcoma cells. Results Data were available, depending on phenotype, for 654-1082 of 1086 female twins (median age 58.9 years; range 46-77). Trends in dietary analysis revealed a specific pattern of dietary intake, that high in fruit and vegetables, showed an inverse association with hip OA (p = 0.022). Consumption of 'non-citrus fruit' (p = 0.015) and 'alliums' (p = 0.029) had the strongest protective effect. Alliums contain diallyl disulphide which was shown to abrogate cytokine-induced matrix metalloproteinase expression. Conclusions Studies of diet are notorious for their confounding by lifestyle effects. While taking account of BMI, the data show an independent effect of a diet high in fruit and vegetables, suggesting it to be protective against radiographic hip OA. Furthermore, diallyl disulphide, a compound found in garlic and other alliums, represses the expression of matrix-degrading proteases in chondrocyte-like cells, providing a potential mechanism of action