2016 — 2017 |
Lee, Hey-Kyoung [⬀] Nielsen, Kristina J. |
R21Activity Code Description: To encourage the development of new research activities in categorical program areas. (Support generally is restricted in level of support and in time.) |
Recovering Plasticity in Adult Ferret V1 by Cross-Modal Deprivation @ Johns Hopkins University
? DESCRIPTION (provided by applicant): Long-term monocular deprivation (MD) initiated before any visual experience leads to permanent loss of vision through the occluded eye, and is much more resistant to recovery later in life compared to MD initiated after a period of normal vision. At a functional and anatomical level, it is known that long-term MD leads to a shift in ocular dominance (OD) in the primary visual cortex (V1). In particular, V1 neurons lose responses from the deprived eye, which are thought to result from mechanisms resembling long-term depression (LTD). While recent studies have reported recovery from long-term MD using either genetic manipulations or invasive pharmacological interventions, these cases have been limited to long-term MD after about a week of normal vision during early development. Studies have shown that MD initiated before eye opening in diverse animal models is much more resilient to recovery, and is thought to involve changes in thalamocortical (TC) inputs to V1. Hence methods to recover plasticity at TC synapses would benefit recovery from chronic long-term MD without initial vision. We recently found that deafening adult mice for a brief duration leads to potentiation of TC synapses in layer 4 (L4) of V1. Here we propose to examine whether deafening adult ferrets for a brief duration would allow cross-modal potentiation of TC synapses in V1 to promote recovery from chronic long-term MD initiated before eye opening. Ferret V1 is organized similar to humans with OD columns and orientation pinwheels, which overcomes the limits of mouse V1 lacking such modular organization. To test our hypothesis that deafening promotes TC plasticity in adult ferret V1, we will utilize channelrhodopsin based optogenetic tools to quantitatively measure the strength of TC synapses in L4 of V1 with or without deafening (Aim 1). In addition, intracortical synaptic strength in L4 will be quantified. T investigate whether cross-modal potentiation of TC synapses promotes recovery from chronic long-term MD, we will compare V1 neuronal functions, including OD and visual acuity, using multi-site laminar recording probes (Aim 2). The results from our study will determine whether cross-modal sensory deprivation in adults would promote recovery from chronic long-term MD by restoring TC plasticity. Our results could be generalized to promote recovery from sensory loss in other modalities, and pave a way to develop non-invasive means to recover from deprivation amblyopia in adults.
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2017 — 2021 |
Nielsen, Kristina J. |
R01Activity Code Description: To support a discrete, specified, circumscribed project to be performed by the named investigator(s) in an area representing his or her specific interest and competencies. |
The Impact of Visual Experience On the Development of the Motion Pathway in the Ferret @ Johns Hopkins University
The perception of complex motion patterns, which requires integration of multiple moving elements, is impaired in a range of developmental disorders. In the brain, processing of complex motion signals is handled by a dedicated visual pathway that includes primary visual cortex (V1) and a higher order motion area. Very little is known about the mechanisms that determine its development, as is the case for most higher level visual functions. Here, we will test one factor likely to play a major role in its development, visual experience. We will investigate when visual experience is required for the motion pathway to develop, and what kind of visual experience is required. We will perform these experiments in the ferret, which has become a major animal model for visual development because of its relative immaturity at birth. The ferret?s motion pathway includes V1 and area PSS, a higher order visual area. We will investigate the influence of visual experience on this pathway in 2 sets of experiments. In the first set of experiments, we will investigate during which time visual experience is required for the motion pathway to develop normally. To this end, we will raise animals either normally, or withhold visual experience for certain time periods. We will then investigate how lack of visual experience impacts the pathway?s function by measuring direction selectivity in V1 and PSS, and signatures of motion integration in V1 and PSS. These experiments will be performed using extracellular recordings in PSS, and two-photon imaging combined with retrograde tracers in V1 to selectively study the responses of PSS- projecting V1 neurons. We will also perform behavioral experiments in adult animals to investigate whether there are lasting consequences on motion perception. We expect to find 2 critical periods during which vision is required, an initial period for the development of direction selectivity, and a later period for motion integration. This would demonstrate that visual experience has a sustained impact on the developing visual system. In a second set of experiments, we will test which kinds of visual experience are required for motion pathway development by testing the impact of different kinds of visual experience on the immature motion pathway. More precisely, we will determine whether complex motion stimuli containing multiple moving elements, simple moving stimuli containing only one moving element, or static stimuli can enhance immature direction selectivity and motion integration. We expect to find that only simple motion, but not static stimuli, can enhance direction selectivity. We also expect to find that complex motion, but none of the other stimuli can enhance motion integration. These findings would demonstrate that different visual functions require different kinds of visual experience for their development. In summary, our experiments would be a systematic investigation of how visual experience impacts the development of an important higher vision pathway. They would contribute important insights into the mechanisms shaping the development of higher visual cortex, and may help identify reasons for the deficits in motion processing observed in a range of developmental disorders.
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2018 — 2021 |
Connor, Charles E Nielsen, Kristina J. |
R01Activity Code Description: To support a discrete, specified, circumscribed project to be performed by the named investigator(s) in an area representing his or her specific interest and competencies. |
Early Representation of 3d Volumetric Shape in Visual Object Processing @ Johns Hopkins University
Project Summary The goal of this project is to test a novel theoretical framework for understanding how the ventral pathway subserves object vision. In the standard framework, a series of neural operations on 2D image data through many intermediate cortical stages, including area V4, leads to high-level perceptual representations, including representation of object identity, at the final stages of the ventral pathway. However, our preliminary microelectrode data from a fixating monkey show that many neurons in V4 represent volumetric (volume- enclosing) 3D shape, not 2D image patterns. These neurons respond to many different 2D images that convey the same 3D shape with different shape-in-depth cues, including shading, reflection, and refraction. They even respond preferentially to random dot stereograms that convey 3D volumetric shape with no 2D cues whatsoever. Moreover, our preliminary results with 2-photon functional imaging in anesthetized monkey V4 show that 3D shape signals are grouped by their similarity, and also group with isomorphic (same outline) 2D shape signals (which could contribute evidence to corresponding 3D shape inferences). We propose to capitalize on these preliminary data by demonstrating the prevalence of 3D shape tuning in area V4, analyzing the 3D shape coding strategies used by these neurons, and measuring how 2D and 3D shape signals are arranged at a microscopic level across the surface of V4. We expect these results to provide strong evidence that extraction of 3D shape fragments is a primary goal of V4 processing. This early extraction of 3D shape information, just two synapses beyond primary visual cortex, would suggest a competing framework for understanding the ventral pathway, in which the initial goal is to represent 3D physical structure, independent of the various 2D image cues used to infer it. In this framework, object recognition would be based on preceding information about 3D physical structure, which would explain why human object recognition is so robust to image changes, in a way that the best computational vision systems are not. The scientific impact of this work would be to divert vision experiments toward understanding representation of real world 3D structure (rather than 2D planar stimuli) and to encourage computational vision scientists to incorporate early 3D shape processing into the deep convolutional network models that are the current state of the art.
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2020 |
Nielsen, Kristina J. |
R13Activity Code Description: To support recipient sponsored and directed international, national or regional meetings, conferences and workshops. |
4th Ferret Brain Meeting @ Johns Hopkins University
Project summary/Abstract This proposal seeks partial support for the 4th Ferret Brain Meeting, which will be held in Baltimore, Maryland, from 10/29 to 10/30/2020. The goal of the Ferret Brain Meeting is to bring together the larger community of neuroscientists working in the ferret. Ferrets offer distinct advantages for neuroscience research ? they have a complex brain, capable of sophisticated processing, with established functional and structural similarities to the primate. At the same time, ferrets share some of the advantages of research in rodents, such as the availability of larger animal numbers, and most recently the development of transgenic animals. Finally, ferrets are uniquely suited for developmental studies because of very early parturition. Research in the ferret spans a diverse range of topics, and the Ferret Brain Meeting is currently the only venue that brings all of the labs together. On the basis of a shared animal model, we will discuss recent research findings and new ideas. An important component is to share technological advances, and to coordinate further tool development efforts. The first transgenic ferret line has recently been developed, but transgenic ferrets will only become widely available if we can combine efforts across labs, and involve commercial ferret breeders as well. In general, we aim to build a strong, collaborative community that significantly benefits and advances the research in all of our labs. An important component of the Ferret Brain Meeting is to promote graduate students and postdocs. Generally, the meeting is single track with many opportunities for participants to interact, which will provide trainees with plenty of opportunity to network. In addition, trainees will present their work in a poster session, and at least 6 of 15 talks at the meeting will be given by trainees. We will honor the best trainee presentation with the Barbara Chapman Young Investigator Award. At the 4th Ferret Brain Meeting, we will also test an outreach program aimed at increasing participation of underrepresented minorities in neuroscience. More specifically, we plan to use the conference as a platform for recruiting undergraduates from these backgrounds to neuroscience. The Ferret Brain Meeting is an exciting opportunity for this effort ? it will not only introduce undergraduates to cutting-edge science, but because of the meeting's small size, it will allow them to meet the involved scientists (faculty and trainees). To start this outreach effort, the organizers of the 4th Ferret Brain Meeting will work with their local institutions to recruit undergraduates to the meeting, but we intend to expand this effort at future meetings.
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