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Search Results: 1 - 10 of 403411 matches for " Gordon M. Shepherd "
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The Human Sense of Smell: Are We Better Than We Think?
Gordon M. Shepherd
PLOS Biology , 2012, DOI: 10.1371/journal.pbio.0020146
The Human Sense of Smell: Are We Better Than We Think?
Gordon M Shepherd
PLOS Biology , 2004, DOI: 10.1371/journal.pbio.0020146
The Microcircuit Concept Applied to Cortical Evolution: from Three-Layer to Six-Layer Cortex
Gordon M. Shepherd
Frontiers in Neuroanatomy , 2011, DOI: 10.3389/fnana.2011.00030
Abstract: 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.
Learning mechanism for column formation in the olfactory bulb
M. Migliore,Carlo Inzirillo,Gordon M. Shepherd
Frontiers in Integrative Neuroscience , 2007, DOI: 10.3389/neuro.07.012.2007
Abstract: 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.
The olfactory receptor family album
Chiquito Crasto, Michael S Singer, Gordon M Shepherd
Genome Biology , 2001, DOI: 10.1186/gb-2001-2-10-reviews1027
Abstract: In the ten years since olfactory receptor genes were first identified [1], these genes and the receptors they encode have attracted growing interest. Olfactory or olfactory-like receptor genes are expressed in high numbers in the olfactory epithelium [1,2,3] but are also found in other tissues as far removed as the testes [4] and heart [5]. This is believed to reflect potentially varied functions for the proteins encoded by these genes.The release of the first draft of the human genome, from the combined efforts of the public [6] and private [7] sectors, provides a new base for research on olfactory receptors and their genes. It is timely to synthesize the earlier work with this new information to provide new insights into the evolution of olfactory receptors and new directions for research on the molecular and neural basis of the sense of smell.Olfactory receptors belong to the superfamily of G-protein-coupled receptors (GPCRs), which are characterized by seven transmembrane helical regions. For years it has been estimated that mammals have some 1,000 olfactory genes [8,9,10], making up the largest family in the genome. The family thus constitutes some 3% of the 31,000 genes now estimated to comprise the human genome. Before the complete draft genome sequence was available, Rouquier et al. [11] identified 72% of a sample of human olfactory receptor genes as pseudogenes (due to frame shifts and stop codons). A follow-up study [12] showed that loss of receptor function by the transformation of functional genes into pseudogenes is relatively common in human and prosimian primates, less common in lower primates, and is rarely found in mouse or zebrafish. The implication is that as species require less olfactory acuity, molecular disruptions accumulate and erode the functionality of olfactory receptor genes. The absence of functional olfactory receptors in the dolphin [13] and the deterioration of vision in moles [14] provide extreme examples of this mechanism, which is
Distributed organization of a brain microcircuit analyzed by three-dimensional modeling: the olfactory bulb
Michele Migliore,Francesco Cavarretta,Michael L. Hines,Gordon M. Shepherd
Frontiers in Computational Neuroscience , 2014, DOI: 10.3389/fncom.2014.00050
Abstract: The functional consequences of the laminar organization observed in cortical systems cannot be easily studied using standard experimental techniques, abstract theoretical representations, or dimensionally reduced models built from scratch. To solve this problem we have developed a full implementation of an olfactory bulb microcircuit using realistic three-dimensional (3D) inputs, cell morphologies, and network connectivity. The results provide new insights into the relations between the functional properties of individual cells and the networks in which they are embedded. To our knowledge, this is the first model of the mitral-granule cell network to include a realistic representation of the experimentally-recorded complex spatial patterns elicited in the glomerular layer (GL) by natural odor stimulation. Although the olfactory bulb, due to its organization, has unique advantages with respect to other brain systems, the method is completely general, and can be integrated with more general approaches to other systems. The model makes experimentally testable predictions on distributed processing and on the differential backpropagation of somatic action potentials in each lateral dendrite following odor learning, providing a powerful 3D framework for investigating the functions of brain microcircuits.
Abnormal excitability of oblique dendrites implicated in early Alzheimer's: a computational study
Thomas M. Morse,Nicholas T. Carnevale,Pradeep G. Mutalik,Michele Migliore,Gordon M. Shepherd
Frontiers in Neural Circuits , 2010, DOI: 10.3389/fncir.2010.00016
Abstract: The integrative properties of cortical pyramidal dendrites are essential to the neural basis of cognitive function, but the impact of amyloid beta protein (aβ) on these properties in early Alzheimer’s is poorly understood. In animal models, electrophysiological studies of proximal dendrites have shown that aβ induces hyperexcitability by blocking A-type K+ currents (IA), disrupting signal integration. The present study uses a computational approach to analyze the hyperexcitability induced in distal dendrites beyond the experimental recording sites. The results show that back-propagating action potentials in the dendrites induce hyperexcitability and excessive calcium concentrations not only in the main apical trunk of pyramidal cell dendrites, but also in their oblique dendrites. Evidence is provided that these thin branches are particularly sensitive to local reductions in IA. The results suggest the hypothesis that the oblique branches may be most vulnerable to disruptions of IA by early exposure to aβ, and point the way to further experimental analysis of these actions as factors in the neural basis of the early decline of cognitive function in Alzheimer’s.
A Framework for Exploring Functional Variability in Olfactory Receptor Genes
Orna Man, David C. Willhite, Chiquito J. Crasto, Gordon M. Shepherd, Yoav Gilad
PLOS ONE , 2007, DOI: 10.1371/journal.pone.0000682
Abstract: Background Olfactory receptors (ORs) are the largest gene family in mammalian genomes. Since nearly all OR genes are orphan receptors, inference of functional similarity or differences between odorant receptors typically relies on sequence comparisons. Based on the alignment of entire coding region sequence, OR genes are classified into families and subfamilies, a classification that is believed to be a proxy for OR gene functional variability. However, the assumption that overall protein sequence diversity is a good proxy for functional properties is untested. Methodology Here, we propose an alternative sequence-based approach to infer the similarities and differences in OR binding capacity. Our approach is based on similarities and differences in the predicted binding pockets of OR genes, rather than on the entire OR coding region. Conclusions Interestingly, our approach yields markedly different results compared to the analysis based on the entire OR coding-regions. While neither approach can be tested at this time, the discrepancy between the two calls into question the assumption that the current classification reliably reflects OR gene functional variability.
Sparse Distributed Representation of Odors in a Large-scale Olfactory Bulb Circuit
Yuguo Yu,Thomas S. McTavish,Michael L. Hines,Gordon M. Shepherd,Cesare Valenti,Michele Migliore
PLOS Computational Biology , 2013, DOI: 10.1371/journal.pcbi.1003014
Abstract: In the olfactory bulb, lateral inhibition mediated by granule cells has been suggested to modulate the timing of mitral cell firing, thereby shaping the representation of input odorants. Current experimental techniques, however, do not enable a clear study of how the mitral-granule cell network sculpts odor inputs to represent odor information spatially and temporally. To address this critical step in the neural basis of odor recognition, we built a biophysical network model of mitral and granule cells, corresponding to 1/100th of the real system in the rat, and used direct experimental imaging data of glomeruli activated by various odors. The model allows the systematic investigation and generation of testable hypotheses of the functional mechanisms underlying odor representation in the olfactory bulb circuit. Specifically, we demonstrate that lateral inhibition emerges within the olfactory bulb network through recurrent dendrodendritic synapses when constrained by a range of balanced excitatory and inhibitory conductances. We find that the spatio-temporal dynamics of lateral inhibition plays a critical role in building the glomerular-related cell clusters observed in experiments, through the modulation of synaptic weights during odor training. Lateral inhibition also mediates the development of sparse and synchronized spiking patterns of mitral cells related to odor inputs within the network, with the frequency of these synchronized spiking patterns also modulated by the sniff cycle.
Mitral cell spike synchrony modulated by dendrodendritic synapse location
Thomas S. McTavish,Michele Migliore,Gordon M. Shepherd,Michael L. Hines
Frontiers in Computational Neuroscience , 2012, DOI: 10.3389/fncom.2012.00003
Abstract: 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.
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