Image above: Tangential Confocal Image 

Functional Architecture and Development of the Cerebral Cortex

The Fitzpatrick Lab is focused on understanding neural circuits in the cerebral cortex, the largest and most complex area of the brain, a neuronal network whose proper function is critical for sensory perception, motor control, and cognition. We use state of the art in vivo imaging techniques to study the synaptic interactions in visual cortex that enable our remarkable abilities to detect, interpret, and interact with the information-rich patterns of light that fall on our retinas. We examine circuit organization at columnar, cellular, and synaptic levels of resolution, probing fundamental questions about cortical function and development.

Recent Publications

Orientation Selectivity and Functional Clustering of Synaptic Inputs in the Primary Visual Cortex

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In this recent publication the authors used two-photon calcium imaging to characterize the orientation tuning and spatial arrangement of synaptic inputs to the dendritic spines of individual neurons in ferret visual cortex. Comparing the dendritic spines and cell body responses, researchers were able to reliably predict the orientation preference of individual neurons by adding the responses of their dendritic spines. However, the responses of the dendritic spines did not account for the degree of orientation selectivity exhibited by individual neurons. The determining factors that could account for these differences in selectivity, appeared to be spines with similar orientation preference that were often spatially clustered along the dendrite and neurons with a greater number of clusters exhibited greater selectivity. Functional clustering was shown to be correlated with localized dendritic events, enhancing the overall impact of the spines.

Research in Progress

Development in Cortical Circuits

Cortical networks that underlie behavior exhibit an orderly functional organization at local and global scales, an organization that is especially evident in the visual cortex of carnivores and primates. Here, neural responses in the mature animal are exquisitely sensitive to stimulus orientation, and organized such that the full range of stimulus orientations is represented in the responses of neighboring columns of neurons contained within a millimeter of cortical surface area. However, local population activity is shaped by a much larger, distributed network of neurons sharing similar response properties. In these proposed experiments, we will conduct a detailed exploration how distributed cortical networks self-organize during early development. As these experiments necessitate being able to track neural activity in the same population over time, we will combine in vivo mesoscopic (columnar) and cellular level imaging with neurons transfected with a genetically encoded sensor. First we will record early population activity in the developing cortex and determine when long-range correlations between neurons become evident. As spontaneous and evoked activity generated in the periphery are also known to play a key role in organizing central pathways, we will also determine how well early activity patterns in visual cortex compare to activity patterns generated after circuit maturation. Throughout this project, we will actively collaborate with a German computational neuroscience group to develop computational models that can explain how local circuits in visual cortex could generate structured correlations between neurons, at a time when long-range horizontal circuitry is still undeveloped.

Mapping Receptive Fields of Dendritic Spines of Layer 2/3 Neurons using Calcium Imaging 

In vivo two-photon imaging (left) of dendritic branch in tree shrew in V1. 

In vivo two-photon imaging (left) of dendritic branch in tree shrew in V1. 

Confocal image of same dendritic branch (tangential section). Blue color indicates axonal terminals labeled by mCerulean.

Confocal image of same dendritic branch (tangential section). Blue color indicates axonal terminals labeled by mCerulean.

    The proposed experiments take advantage of the latest developments in in vivo imaging technologies and genetically encoded calcium sensors to provide the first detailed analysis of the functional synaptic architecture that is responsible for building the complex response properties of neurons in visual cortex. These experiments will determine the functional specificity of synaptic inputs that a neuron receives and how these inputs compare with the properties of the receptive field center and surround. Equally important, these experiments will determine the spatial organization of functionally defined synaptic inputs within the dendritic tree, providing the first direct test of the hypothesis that dendritic topology contributes significantly to somatic receptive field structure. 

Accessible Science: Videos depicting the Lab's recent Publications 

There is more to dendrites than meets the eye: cluster synaptic inputs and orientation selectivity.

From retina to cortex: An unexpected division of labor.

Luminance polarity in the superficial layers of the primary visual cortex