The expanding functional roles and signaling mechanisms of adhesion G protein–coupled receptors

The adhesion class of G protein–coupled receptors (GPCRs) is the second largest family of GPCRs (33 members in humans). Adhesion GPCRs (aGPCRs) are defined by a large extracellular N‐terminal region that is linked to a C‐terminal seven transmembrane (7TM) domain via a GPCR‐autoproteolysis inducing (GAIN) domain containing a GPCR proteolytic site (GPS). Most aGPCRs undergo autoproteolysis at the GPS motif, but the cleaved fragments stay closely associated, with the N‐terminal fragment (NTF) bound to the 7TM of the C‐terminal fragment (CTF). The NTFs of most aGPCRs contain domains known to be involved in cell–cell adhesion, while the CTFs are involved in classical G protein signaling, as well as other intracellular signaling. In this workshop report, we review the most recent findings on the biology, signaling mechanisms, and physiological functions of aGPCRs

Predicted contextual modulation varies with distance from pinwheel centers in the orientation preference map

In the primary visual cortex (V1) of some mammals, columns of neurons with the full range of orientation preferences converge at the center of a pinwheel-like arrangement, the ‘pinwheel center' (PWC). Because a neuron receives abundant inputs from nearby neurons, the neuron's position on the cortical map likely has a significant impact on its responses to the layout of orientations inside and outside its classical receptive field (CRF). To understand the positional specificity of responses, we constructed a computational model based on orientation preference maps in monkey V1 and hypothetical neuronal connections. The model simulations showed that neurons near PWCs displayed weaker but detectable orientation selectivity within their CRFs, and strongly reduced contextual modulation from extra-CRF stimuli, than neurons distant from PWCs. We suggest that neurons near PWCs robustly extract local orientation within their CRF embedded in visual scenes, and that contextual information is processed in regions distant from PWCs

New technologies for examining neuronal ensembles in drug addiction and fear

Correlational data suggest that learned associations are encoded within neuronal ensembles. However, it has been difficult to prove that neuronal ensembles mediate learned behaviours because traditional pharmacological and lesion methods, and even newer cell type-specific methods, affect both activated and non-activated neurons. Additionally, previous studies on synaptic and molecular alterations induced by learning did not distinguish between behaviourally activated and non-activated neurons. Here, we describe three new approaches—Daun02 inactivation, FACS sorting of activated neurons and c-fos-GFP transgenic rats — that have been used to selectively target and study activated neuronal ensembles in models of conditioned drug effects and relapse. We also describe two new tools — c-fos-tTA mice and inactivation of CREB-overexpressing neurons — that have been used to study the role of neuronal ensembles in conditioned fear

Involvement of the Adhesion GPCRs Latrophilins in the Regulation of Insulin Release

Summary: Insulin secretion from pancreatic β cells is a highly complex and tightly regulated process. Its dysregulation is one characteristic of type 2 diabetes, and thus, an in-depth understanding of the mechanisms controlling insulin secretion is essential for rational therapeutic intervention. G-protein-coupled receptors (GPCRs) have been established as major regulators of insulin exocytosis. Recent studies also suggest the involvement of adhesion GPCRs, a non-prototypical class of GPCRs. Here, we identify latrophilins, which belong to the class of adhesion GPCRs, to be highly expressed in different cell types of pancreatic islets. In vitro and ex vivo analyses show that distinct splice variants of the latrophilin LPHN3/ADGRL3 decrease insulin secretion from pancreatic β cells by reducing intracellular cyclic AMP levels via the Gi-mediated pathway. Our data highlight the key role of LPHN3 in modulating insulin secretion and its potential as therapeutic target for type 2 diabetes. : With diabetes becoming an epidemic disease, understanding processes regulating insulin secretion is a major task. Röthe et al. show that tissue-specific splice variants of the adhesion GPCR Latrophilin-3 in pancreatic islets modulate insulin secretion. In contrast to other variants, they reduce intracellular cAMP via a Gi protein pathway. Keywords: adhesion GPCRs, latrophilins, insulin secretion, signaling, splice variant

Tospovirus ambisense genomic RNA segments use almost complete repertoire of stable tetraloops in the intergenic region

Supramolecular & Biomaterials Chemistr

Sparse orthogonal population representation of spatial context in the retrosplenial cortex

Sparse orthogonal coding is a key feature of hippocampal neural activity, which is believed to increase episodic memory capacity and to assist in navigation. Some retrosplenial cortex (RSC) neurons convey distributed spatial and navigational signals, but place-field representations such as observed in the hippocampus have not been reported. Combining cellular Ca2+ imaging in RSC of mice with a head-fixed locomotion assay, we identified a population of RSC neurons, located predominantly in superficial layers, whose ensemble activity closely resembles that of hippocampal CA1 place cells during the same task. Like CA1 place cells, these RSC neurons fire in sequences during movement, and show narrowly tuned firing fields that form a sparse, orthogonal code correlated with location. RSC 'place' cell activity is robust to environmental manipulations, showing partial remapping similar to that observed in CA1. This population code for spatial context may assist the RSC in its role in memory and/or navigation.Neurons in the retrosplenial cortex (RSC) encode spatial and navigational signals. Here the authors use calcium imaging to show that, similar to the hippocampus, RSC neurons also encode place cell-like activity in a sparse orthogonal representation, partially anchored to the allocentric cues on the linear track

The cognitive map in humans: spatial navigation and beyond

The ‘cognitive map’ hypothesis proposes that brain builds a unified representation of the spatial environment to support memory and guide future action. Forty years of electrophysiological research in rodents suggests that cognitive maps are neurally instantiated by place, grid, border, and head direction cells in the hippocampal formation and related structures. Here we review recent work that suggests a similar functional organization in the human brain and reveals novel insights into how cognitive maps are used during spatial navigation. Specifically, these studies indicate that: (i) the human hippocampus and entorhinal cortex support map-like spatial codes; (ii) posterior brain regions such as parahippocampal and retrosplenial cortices provide critical inputs that allow cognitive maps to be anchored to fixed environmental landmarks; (iii) hippocampal and entorhinal spatial codes are used in conjunction with frontal lobe mechanisms to plan routes during navigation. We also discuss how these three basic elements of cognitive map based navigation—spatial coding, landmark anchoring, and route planning—might be applied to non-spatial domains to provide the building blocks for many core elements of human thought