RESUMO
Columnar organization of orientation selectivity and clustered horizontal connections linking orientation columns are two of the distinctive organizational features of primary visual cortex in many mammalian species. However, the functional role of these connections has been harder to characterize. Here we examine the extent and nature of horizontal interactions in V1 of the tree shrew using optical imaging of intrinsic signals, optogenetic stimulation, and multi-unit recording. Surprisingly, we find the effects of optogenetic stimulation depend primarily on distance and not on the specific orientation domains or axes in the cortex, which are stimulated. In addition, across a wide range of variation in both visual and optogenetic stimulation we find linear addition of the two inputs. These results emphasize that the cortex provides a rich substrate for functional interactions that are not limited to the orientation-specific interactions predicted by the monosynaptic distribution of horizontal connections.
Assuntos
Optogenética , Orientação/fisiologia , Córtex Visual/fisiologia , Vias Visuais/fisiologia , Potenciais de Ação/fisiologia , Animais , Proteína Quinase Tipo 2 Dependente de Cálcio-Calmodulina/genética , Proteína Quinase Tipo 2 Dependente de Cálcio-Calmodulina/metabolismo , Antagonistas de Aminoácidos Excitatórios/farmacologia , Feminino , Proteínas Luminescentes/genética , Proteínas Luminescentes/metabolismo , Masculino , Microscopia Confocal , Neurônios/fisiologia , Estimulação Luminosa , Quinoxalinas/farmacologia , Rodopsina/genética , Rodopsina/metabolismo , Sinapsinas/genética , Sinapsinas/metabolismo , Tupaiidae , Valina/análogos & derivados , Valina/farmacologia , Córtex Visual/citologiaRESUMO
MOTIVATION: Advances in the field of cheminformatics have been hindered by a lack of freely available tools. We have created Chembench, a publicly available cheminformatics portal for analyzing experimental chemical structure-activity data. Chembench provides a broad range of tools for data visualization and embeds a rigorous workflow for creating and validating predictive Quantitative Structure-Activity Relationship models and using them for virtual screening of chemical libraries to prioritize the compound selection for drug discovery and/or chemical safety assessment. AVAILABILITY: Freely accessible at: http://chembench.mml.unc.edu CONTACT: alex_tropsha@unc.edu
Assuntos
Descoberta de Drogas , Software , Biologia Computacional , Relação Quantitativa Estrutura-Atividade , Bibliotecas de Moléculas Pequenas , Relação Estrutura-AtividadeRESUMO
Functional circuits in the visual cortex require the coordinated activity of excitatory and inhibitory neurons. Molecular genetic approaches in the mouse have led to the "local non-specific pooling principle" of inhibitory connectivity, in which inhibitory neurons are untuned for stimulus features due to the random pooling of local inputs. However, it remains unclear whether this principle generalizes to species with a columnar organization of feature selectivity such as carnivores, primates, and humans. Here we use virally mediated GABAergic-specific GCaMP6f expression to demonstrate that inhibitory neurons in ferret visual cortex respond robustly and selectively to oriented stimuli. We find that the tuning of inhibitory neurons is inconsistent with the local non-specific pooling of excitatory inputs and that inhibitory neurons exhibit orientation-specific noise correlations with local and distant excitatory neurons. These findings challenge the generality of the non-specific pooling principle for inhibitory neurons, suggesting different rules for functional excitatory-inhibitory interactions in non-murine species.