Intrinsic electrophysiological properties of entorhinal cortex stellate cells and their contribution to grid cell firing fields

The medial entorhinal cortex (MEC) is an increasingly important focus for investigation of mechanisms for spatial representation. Grid cells found in layer II of the MEC are likely to be stellate cells, which form a major projection to the dentate gyrus. Entorhinal stellate cells are distinguished by distinct intrinsic electrophysiological properties, but how these properties contribute to representation of space is not yet clear. Here, we review the ionic conductances, synaptic, and excitable properties of stellate cells, and examine their implications for models of grid firing fields. We discuss why existing data are inconsistent with models of grid fields that require stellate cells to generate periodic oscillations. An alternative possibility is that the intrinsic electrophysiological properties of stellate cells are tuned specifically to control integration of synaptic input. We highlight recent evidence that the dorsal-ventral organization of synaptic integration by stellate cells, through differences in currents mediated by HCN and leak potassium channels, influences the corresponding organization of grid fields. Because accurate cellular data will be important for distinguishing mechanisms for generation of grid fields, we introduce new data comparing properties measured with whole-cell and perforated patch-clamp recordings. We find that clustered patterns of action potential firing and the action potential after-hyperpolarization (AHP) are particularly sensitive to recording condition. Nevertheless, with both methods, these properties, resting membrane properties and resonance follow a dorsal-ventral organization. Further investigation of the molecular basis for synaptic integration by stellate cells will be important for understanding mechanisms for generation of grid fields

Rural income in the People's Republic of China, 1952 to 1957, with special reference to Guangdong Province.

This thesis analyzes aspects of rural income in the South Chinese province of Guangdong during the period 1952 to 1957. Its focus is upon rural personal income, i.e. income in cash and in kind available to rural dwellers for the consumption of goods and services. It uses primarily Chinese language materials, of which the most important is the daily newspaper of Guangdong province, the Nan-fang Ri-bao (Southern Daily). It examines five related issues. (1) The average level of personal income of the Guangdong farm population in the mid-1950's: this is looked at in financial terms, in terms both of the level of consumption of goods and services that it provided, and the energy consumption given by the food intake. (2) Changes in the average level of rural income between 1952 and 1957. Here the author analyzes changes in farm output, in the conditions of disposal of farm output as well as direct evidence on changes in the average level of personal income. (3) The relationship between urban and rural incomes: the author examines the extent of the gap in personal income between the two sectors in the mid-1950's, looks at evidence on changer in the gap between 1952 and 1957, and at government policy towards the issue. (4) The spatial aspect of rural income inequality: the inherited structure of regional inequality in the province is outlined, and an assessment made of the impact upon this of the economic policies of the post-1949 government. (5) Inequality of income within, the village: the author outlines briefly the nature of the inherited structure in Guangdong's villages, and examines the impact on this of three phases in post-1949 policy-land reform, the period .from the end of land reform to collectivisation, and collectivisation itself. In the conclusion to the thesis the author summarises his results for the period 1952 to 1957, and outlines the long-run experience of the province in the 1960's and 1970's in respect to these same issues

Feedback inhibition enables theta-nested gamma oscillations and grid firing fields

Cortical circuits are thought to multiplex firing rate codes with temporal codes that rely on oscillatory network activity, but the circuit mechanisms that combine these coding schemes are unclear. We establish with optogenetic activation of layer II of the medial entorhinal cortex that theta frequency drive to this circuit is sufficient to generate nested gamma frequency oscillations in synaptic activity. These nested gamma oscillations closely resemble activity during spatial exploration, are generated by local feedback inhibition without recurrent excitation, and have clock-like features suitable as reference signals for multiplexing temporal codes within rate-coded grid firing fields. In network models deduced from our data, feedback inhibition supports coexistence of theta-nested gamma oscillations with attractor states that generate grid firing fields. These results indicate that grid cells communicate primarily via inhibitory interneurons. This circuit mechanism enables multiplexing of oscillation-based temporal codes with rate-coded attractor states

Inter- and intra-animal variation of integrative properties of stellate cells in the medial entorhinal cortex

Funding Information: We thank Vanessa Stempel for comments on the manuscript, Tor Stensola and Edvard Moser for sharing published data, and Lukas Solanka and Lukas Fischer for help with building the large cage. This work was supported by grants to MN from the Wellcome Trust (200855/Z/16/Z) and the BBSRC (BB/L010496/1, BB/1022147/1 and BB/H020284/1). Publisher Copyright: © 2020, eLife Sciences Publications Ltd. All rights reserved.Peer reviewedPublisher PD

Key scientific challenges in current rechargeable non-aqueous Li-O2 batteries: experiment and theory

Rechargeable Li–air (henceforth referred to as Li–O2) batteries provide theoretical capacities that are ten times higher than that of current Li-ion batteries, which could enable the driving range of an electric vehicle to be comparable to that of gasoline vehicles. These high energy densities in Li–O2 batteries result from the atypical battery architecture which consists of an air (O2) cathode and a pure lithium metal anode. However, hurdles to their widespread use abound with issues at the cathode (relating to electrocatalysis and cathode decomposition), lithium metal anode (high reactivity towards moisture) and due to electrolyte decomposition. This review focuses on the key scientific challenges in the development of rechargeable non-aqueous Li–O2 batteries from both experimental and theoretical findings. This dual approach allows insight into future research directions to be provided and highlights the importance of combining theoretical and experimental approaches in the optimization of Li–O2 battery systems

GABAergic Projections from the Medial Septum Selectively Inhibit Interneurons in the Medial Entorhinal Cortex

The medial septum (MS) is required for theta rhythmic oscillations and grid cell firing in the medial entorhinal cortex (MEC). While GABAergic, glutamatergic, and cholinergic neurons project from the MS to the MEC, their synaptic targets are unknown. To investigate whether MS neurons innervate specific layers and cell types in the MEC, we expressed channelrhodopsin-2 in mouse MS neurons and used patch-clamp recording in brain slices to determine the response to light activation of identified cells in the MEC. Following activation of MS axons, we observed fast monosynaptic GABAergic IPSPs in the majority (>60%) of fast-spiking (FS) and low-threshold-spiking (LTS) interneurons in all layers of the MEC, but in only 1.5% of nonstellate principal cells (NSPCs) and in no stellate cells. We also observed fast glutamatergic responses to MS activation in a minority (<5%) of NSPCs, FS, and LTS interneurons. During stimulation of MS inputs at theta frequency (10 Hz), the amplitude of GABAergic IPSPs was maintained, and spike output from LTS and FS interneurons was entrained at low (25–60 Hz) and high (60–180 Hz) gamma frequencies, respectively. By demonstrating cell type-specific targeting of the GABAergic projection from the MS to the MEC, our results support the idea that the MS controls theta frequency activity in the MEC through coordination of inhibitory circuits

Antibody binding loop insertions as diversity elements

In the use of non-antibody proteins as affinity reagents, diversity has generally been derived from oligonucleotide-encoded random amino acids. Although specific binders of high-affinity have been selected from such libraries, random oligonucleotides often encode stop codons and amino acid combinations that affect protein folding. Recently it has been shown that specific antibody binding loops grafted into heterologous proteins can confer the specific antibody binding activity to the created chimeric protein. In this paper, we examine the use of such antibody binding loops as diversity elements. We first show that we are able to graft a lysozyme-binding antibody loop into green fluorescent protein (GFP), creating a fluorescent protein with lysozyme-binding activity. Subsequently we have developed a PCR method to harvest random binding loops from antibodies and insert them at predefined sites in any protein, using GFP as an example. The majority of such GFP chimeras remain fluorescent, indicating that binding loops do not disrupt folding. This method can be adapted to the creation of other nucleic acid libraries where diversity is flanked by regions of relative sequence conservation, and its availability sets the stage for the use of antibody loop libraries as diversity elements for selection experiments

Explaining Institutional Change: Why Elected Politicians Implement Direct Democracy

In existing models of direct democratic institutions, the median voter benefits, but representative politicians are harmed since their policy choices can be overridden. This is a puzzle, since representative politicians were instrumental in creating these institutions. I build a model of direct democracy that explains why a representative might benefit from tying his or her own hands in this way. The key features are (1) that voters are uncertain about their representative's preferences; (2) that direct and representative elections are complementary ways for voters to control outcomes. The model shows that some politicians benefit from the introduction of direct democracy, since they are more likely to survive representative elections: direct democracy credibly prevents politicians from realising extreme outcomes. Historical evidence from the introduction of the initiative, referendum and recall in America broadly supports the theory, which also explains two empirical results that have puzzled scholars: legislators are trusted less, but reelected more, in US states with direct democracy. I conclude by discussing the potential for incomplete information and signaling models to improve our understanding of institutional change more generally