The Microcircuit Concept Applied to Cortical Evolution: from Three-Layer to Six-Layer Cortex

Understanding the principles of organization of the cerebral cortex requires insight into its evolutionary history. This has traditionally been the province of anatomists, but evidence regarding the microcircuit organization of different cortical areas is providing new approaches to this problem. Here we use the microcircuit concept to focus first on the principles of microcircuit organization of three-layer cortex in the olfactory cortex, hippocampus, and turtle general cortex, and compare it with six-layer neocortex. From this perspective it is possible to identify basic circuit elements for recurrent excitation and lateral inhibition that are common across all the cortical regions. Special properties of the apical dendrites of pyramidal cells are reviewed that reflect the specific adaptations that characterize the functional operations in the different regions. These principles of microcircuit function provide a new approach to understanding the expanded functional capabilities elaborated by the evolution of the neocortex

Intracortical Cartography in an Agranular Area

A well-defined granular layer 4 is a defining cytoarchitectonic feature associated with sensory areas of mammalian cerebral cortex, and one with hodological significance: the local axons ascending from cells in thalamorecipient layer 4 and connecting to layer 2/3 pyramidal neurons form a major feedforward excitatory interlaminar projection. Conversely, agranular cortical areas, lacking a distinct layer 4, pose a hodological conundrum: without a laminar basis for the canonical layer 4→2/3 pathway, what is the basic circuit organization? This review highlights current challenges and prospects for local-circuit electroanatomy and electrophysiology in agranular cortex, focusing on the mouse. Different lines of evidence, drawn primarily from studies of motor areas in frontal cortex in rodents, support the view that synaptic circuits in agranular cortex are organized around prominent descending excitatory layer 2/3→5 pathways targeting multiple classes of projection neurons

3D-printer visualization of neuron models

Neurons come in a wide variety of shapes and sizes. In a quest to understand this neuronal diversity, researchers have three-dimensionally traced tens of thousands of neurons; many of these tracings are freely available through online repositories like NeuroMorpho.Org and ModelDB. Tracings can be visualized on the computer screen, used for statistical analysis of the properties of different cell types, used to simulate neuronal behavior, and more. We introduce the use of 3D printing as a technique for visualizing traced morphologies. Our method for generating printable versions of a cell or group of cells is to expand dendrite and axon diameters and then to transform the wireframe tracing into a 3D object with a neuronal surface generating algorithm like Constructive Tessellated Neuronal Geometry (CTNG). We show that 3D printed cells can be readily examined, manipulated, and compared with other neurons to gain insight into both the biology and the reconstruction process. We share our printable models in a new database, 3DModelDB, and encourage others to do the same with cells that they generate using our code or other methods. To provide additional context, 3DModelDB provides a simulatable version of each cell, links to papers that use or describe it, and links to associated entries in other databases

Learning Mechanism for Column Formation in the Olfactory Bulb

Sensory discrimination requires distributed arrays of processing units. In the olfactory bulb, the processing units for odor discrimination are believed to involve dendrodendritic synaptic interactions between mitral and granule cells. There is increasing anatomical evidence that these cells are organized in columns, and that the columns processing a given odor are arranged in widely distributed arrays. Experimental evidence is lacking on the underlying learning mechanisms for how these columns and arrays are formed. To gain insight into these mechanisms, we have used a simplified realistic circuit model to test the hypothesis that distributed connectivity can self-organize through an activity-dependent dendrodendritic synaptic mechanism. The results point to action potentials propagating in the mitral cell lateral dendrites as playing a critical role in this mechanism. The model predicts that columns emerge from the interaction between the local temporal dynamics of the action potentials and the synapses that they activate during dendritic propagation. The results suggest a novel and robust learning mechanism for the development of distributed processing units in a cortical structure

A rank based social norms model of how people judge their levels of drunkenness whilst intoxicated

Background: A rank based social norms model predicts that drinkers’ judgements about their drinking will be based on the rank of their breath alcohol level amongst that of others in the immediate environment, rather than their actual breath alcohol level, with lower relative rank associated with greater feelings of safety. This study tested this hypothesis and examined how people judge their levels of drunkenness and the health consequences of their drinking whilst they are intoxicated in social drinking environments. Methods: Breath alcohol testing of 1,862 people (mean age = 26.96 years; 61.86 % male) in drinking environments. A subset (N = 400) also answered four questions asking about their perceptions of their drunkenness and the health consequences of their drinking (plus background measures). Results: Perceptions of drunkenness and the health consequences of drinking were regressed on: (a) breath alcohol level, (b) the rank of the breath alcohol level amongst that of others in the same environment, and (c) covariates. Only rank of breath alcohol level predicted perceptions: How drunk they felt (b 3.78, 95 % CI 1.69 5.87), how extreme they regarded their drinking that night (b 3.7, 95 % CI 1.3 6.20), how at risk their long-term health was due to their current level of drinking (b 4.1, 95 % CI 0.2 8.0) and how likely they felt they would experience liver cirrhosis (b 4.8. 95 % CI 0.7 8.8). People were more influenced by more sober others than by more drunk others. Conclusion: Whilst intoxicated and in drinking environments, people base judgements regarding their drinking on how their level of intoxication ranks relative to that of others of the same gender around them, not on their actual levels of intoxication. Thus, when in the company of others who are intoxicated, drinkers were found to be more likely to underestimate their own level of drinking, drunkenness and associated risks. The implications of these results, for example that increasing the numbers of sober people in night time environments could improve subjective assessments of drunkenness, are discussed

Issues in the Design of a Pilot Concept-Based Query Interface for the Neuroinformatics Information Framework

This paper describes a pilot query interface that has been constructed to help us explore a "concept-based" approach for searching the Neuroscience Information Framework (NIF). The query interface is concept-based in the sense that the search terms submitted through the interface are selected from a standardized vocabulary of terms (concepts) that are structured in the form of an ontology. The NIF contains three primary resources: the NIF Resource Registry, the NIF Document Archive, and the NIF Database Mediator. These NIF resources are very different in their nature and therefore pose challenges when designing a single interface from which searches can be automatically launched against all three resources simultaneously. The paper first discusses briefly several background issues involving the use of standardized biomedical vocabularies in biomedical information retrieval, and then presents a detailed example that illustrates how the pilot concept-based query interface operates. The paper concludes by discussing certain lessons learned in the development of the current version of the interface

The NIF LinkOut Broker: A Web Resource to Facilitate Federated Data Integration using NCBI Identifiers

This paper describes the NIF LinkOut Broker (NLB) that has been built as part of the Neuroscience Information Framework (NIF) project. The NLB is designed to coordinate the assembly of links to neuroscience information items (e.g., experimental data, knowledge bases, and software tools) that are (1) accessible via the Web, and (2) related to entries in the National Center for Biotechnology Information’s (NCBI’s) Entrez system. The NLB collects these links from each resource and passes them to the NCBI which incorporates them into its Entrez LinkOut service. In this way, an Entrez user looking at a specific Entrez entry can LinkOut directly to related neuroscience information. The information stored in the NLB can also be utilized in other ways. A second approach, which is operational on a pilot basis, is for the NLB Web server to create dynamically its own Web page of LinkOut links for each NCBI identifier in the NLB database. This approach can allow other resources (in addition to the NCBI Entrez) to LinkOut to related neuroscience information. The paper describes the current NLB system and discusses certain design issues that arose during its implementation

Mitral cell spike synchrony modulated by dendrodendritic synapse location

On their long lateral dendrites, mitral cells of the olfactory bulb form dendrodendritic synapses with large populations of granule cell interneurons. The mitral-granule cell microcircuit operating through these reciprocal synapses has been implicated in inducing synchrony between mitral cells. However, the specific mechanisms of mitral cell synchrony operating through this microcircuit are largely unknown and are complicated by the finding that distal inhibition on the lateral dendrites does not modulate mitral cell spikes. In order to gain insight into how this circuit synchronizes mitral cells within its spatial constraints, we built on a reduced circuit model of biophysically realistic multi-compartment mitral and granule cells to explore systematically the roles of dendrodendritic synapse location and mitral cell separation on synchrony. The simulations showed that mitral cells can synchronize when separated at arbitrary distances through a shared set of granule cells, but synchrony is optimally attained when shared granule cells form two balanced subsets, each subset clustered near to a soma of the mitral cell pairs. Another constraint for synchrony is that the input magnitude must be balanced. When adjusting the input magnitude driving a particular mitral cell relative to another, the mitral-granule cell circuit served to normalize spike rates of the mitral cells while inducing a phase shift or delay in the more weakly driven cell. This shift in phase is absent when the granule cells are removed from the circuit. Our results indicate that the specific distribution of dendrodendritic synaptic clusters is critical for optimal synchronization of mitral cell spikes in response to their odor input