Michael Hawken - US grants

The principal aims of this project are to integrate information from the spatial, temporal, directional and binocular domains, derived from responses to achromatic stimuli, into physiologically based descriptions of V1 receptive fields (r.f.'s) and to use this multidimensional assessment to characterize neurons within the different layers and sublayers of V1. It is also proposed to extend the difference of Gaussians based spatial model of r.f. structure to include temporal parameters. In initial experiments the spatial, spatial frequency and orientation tuning of V1 neurons will be measured over a range of temporal modulations of the stimulus. A full spatiotemporal tuning function will be obtained for each neuron using a threshold tracking method. In addition, response- contrast functions will be measured at selected points over the spatiotemporal surface to obtain estimates of the contrast gain and the extent of the compressive contrast non-linearity. In a second series of experiments, monocular and binocular tuning will be measured and compared, using sinewave grating stimuli. Dichoptic presentation will be used to determine binocular interaction at different spatial phases, spatial frequencies and contrasts. In some experiments, disparity sensitivity will be measured. The third part of this proposal is to apply the detailed quantitative measures in the spatial, temporal and binocular domains to categorize cells and determine the distribution of the functional classes both within and across different cortical layers. It is intended to concentrate on the major output layers, layers 2 + 3, 4b, 5 and 6 all of which have distinct extrastriate or sub-cortical targets. These experiments will give a comprehensive description of the properties of the neurons providing afferent input to specific extrastroate areas and therefore the limits of information available to these areas from V1. The relationship between r.f. size and eccentricity will be investigated along with the underlying density of cone photoreceptors. The aim is to obtain measures of local spatial scale as well as to examine whether any differences in local spatial scale, particularly in the foveal region, can be related to the cone distribution. In many forms of amblyopia there is a severe disruption of performance on spatial and binocular tasks, and it is thought that the primary neural locus of the disfunction is the striate cortex. The multidimensional quantitative description of r.f. properties will be important in defining the expected limits of performance of different cell types in different layers in V1 of the adult macaque and is therefore basic to the understanding and treatment of the developmental disorders affecting the central visual pathways.

Software will be developed that provides experimental control of stimulus display and data acquisition in neurophysiological and psychophysical investigations of visual processing. This software is being developed for three main reasons: (1) to take advantage of advances in computer technology that facilitate the development of such systems, (2) to incorporate an extensive library of low- level visual display drivers that have been developed at NYU over the past five years, and (3) to incorporate modern design concepts into the software. The software is expected to provide the basic experimental control program for the next 5-10 years for the research group involved in this proposal. In addition, a key design feature of the software system is portability, with the goal of freeing its general structure from dependance on a specific processor architecture or on a particular set of input and output devices. The common theme of the research that will initially use the newly developed software is that it relies upon computer controlled generation and display of visual patterns, either on monochrome or color monitors along with the collection of stimulus-evoked behavioral and neural responses. Although the initial effort will concentrate on the generation of software for visual experimentation, the design of the system is by no means limited to this area, and adaptation of the general control structures to a wide range of neural and behavioral experiments should be straightforward.

[unreadable] DESCRIPTION (provided by applicant): Understanding how the circuits of the cortex are organized and how they function is a central goal of neuroscience. We have been studying the primary visual cortex, V1, in order to understand its role in vision and also because V1 is one of the best understood regions of the cerebral cortex. On one hand we often have detailed knowledge of the receptive field properties of neurons determined from neuronal firing in V1, to an array of visual stimuli, obtained from extracellular recording. On the other hand from anatomical studies we know about the intricate neuronal architecture and patterns of synaptic connections both within V1 and between V1 and extrastriate cortex. Our proposal aims to bridge the gap between the structure of neurons in circuits in monkey primary visual cortex and their receptive field properties. We use a method called loose-patch juxtacellular recording to monitor extracellular action potentials, that enables us to functionally characterize the RF of the neurons, and then we label same neuron with a tracer molecule and subsequently recover and reconstruct the three dimensional dendritic and axonal arbors of the labeled neurons. Layer 4a, the main target of the magnocellular afferents from the lateral geniculate nucleus, provides input to layer 4b. Both layers have a variety of neurons with distinct morphologies. There is also a range of receptive field properties in the two layers. Our first aim is to characterize the excitatory neurons in layers 4ca and 4b. We will test the hypothesis that there are distinct functional characteristics that associate with distinct morphological types. Among the pyramidal neurons of layer 6 there are distinct classes of neurons based on their pattern of intra-cortical axonal arborization. The axonal patterns are linked to the (vi- and P-cell divisions of layer 4. We will use functional tests that allow us to determine whether labeled neurons are dominated by magnocellular or parvocellular input in addition to tuning for orientation, spatial frequency, temporal frequency and size. Our second aim is to test to what degree morphological classes have specific functional labels, how pathway specific information such as motion and color are retained within different cortical circuits and the extent to which summation and surround suppression are represented within the population of identified neurons. Inhibitory neurons are thought to play specific roles in determining the emergent properties of V1 receptive fields such as orientation, direction and size selectivity. The extent or degree of tuning among the excitatory and inhibitory populations is unknown. Our third aim is to characterize inhibitory neurons in the input and infragranular layers of cortex. There are numerous disorders that are a result of structure-function abnormalities in cortical circuits including, amblyopia, epilepsy and schizophrenia. Understanding how the normal circuits operate provides opportunities for understanding neuronal abnormalities. [unreadable] [unreadable] [unreadable]

DESCRIPTION (provided by applicant): The Center for Neural Science (CNS), the Department of Biology and the Department of Psychology are the primary locus of teaching and research in neuroscience, biological and behavioral sciences at the Washington Square campus of New York University (NYU). Over the last ten years New York University has promoted initiatives in genomics with a strong component in the genetic basis of behavior, in functional brain imaging, and in computation. These have involved joint contributions from the Departments of Biology, Psychology and CNS. These developments are part of a strategic plan to promote excellence in brain science from genetics, molecular biology, systems neuroscience, and computation to behavior. This grant application addresses necessary facility improvements at NYU's two main animal facilities at the Washington Square Campus (Silver and Meyer) critical to support funded investigators in Neural Science, Biology, and associated departments of the University and to continue improvements in the existing facilities and program that will result in AAALAC Accreditation. To support increasing use of mouse models 12 OptiMice ventilated cage systems are requested to supplement current existing caging. Procurement and installation of a new cage and rack washer is requested to replace a marginally operating 10 year old machine. Facility renovation of existing space is proposed to increase capability for primate housing and increase space for food, bedding, cage preparation and storage.

DESCRIPTION (provided by applicant): A central goal of large scale neuroscience initiatives is to provide a functional and structural description of the canonical cortical column that will generalize across columns, cortical regions, and species. One of the most studied columns is in mammalian visual cortex, where the thalamocortical (TC) input projects to layer 4 of cortex. Prior neuroanatomical studies suggest the number of the TC inputs is low (<10% of total input) - hence weak and sparse - which has led to theories requiring strong recurrent amplification from intracortical (IC) afferents to achieve observed response levels. Based on refined immunohistochemical processing and innovative serial electronmicroscopic techniques, our preliminary results indicate that the weak and sparse theories need substantial revision. We find that TC input is not as sparse as previously estimated, but more importantly the 3D reconstruction of TC terminals shows they have a volume 4 -10 times greater than IC terminals. In the current proposal we will use new techniques to characterize the major synaptic inputs in two crucial gateways in the cortical microcircuit, layers 4 and 2/3. In Aim 1 we will measure the number and 3D size of TC and IC terminals in layer 4, as well as the number of vesicles and size of regions of postysynaptic density. The expected outcome is that individual TC efficacy based on size and vesicle number will be greater than individual IC efficacy. This suggests that the population of TC terminals onto layer 4 neurons will be equally effective as the larger population of smaller IC terminals: a result with major implications for models using large scale recurrent amplification. In Aim 2 we will compare the number, size and vesicle density of terminals arising from feed-forward (FF) input from layer 4 to layer 2/3, and from feed-back (FB) terminals arising from intra-cortical lateral feedback (IC FB) or interareal (IA FB) feedback to neurons in layer 2/3. The different populations will be revealed by microinjection of anterograde tracer into layer 2/3 or 4 of area 17, and extrastriate areas 18 or Ssy. The expected outcome is that FF inputs will be larger and more numerous than either FB population: providing the synaptic weight assignment within the canonical microcircuit. Overall our goal is to establish a set of techniques (immunohistochemistry and FIB/SEM) that will enable quantitative comparisons among areas and species of the fine structure of cortical circuits.

Abstract The Neuroanatomy Module provides essential support for the Vision Core in three main areas: 1) Histological and immunohistochemical tissue processing; 2) Anatomical imaging, data acquisition and image analysis; 3) Preparation of viral vectors for optogenetic manipulation of neuronal signals. The Neuroanatomy Module provides moderate or extensive support for 8 members of the Vision Core, including one young investigator and 6 NEI funded investigators, 3 of whom hold qualifying grants.