1986 — 1988 |
Hirsch, Judith A |
F32Activity Code Description: To provide postdoctoral research training to individuals to broaden their scientific background and extend their potential for research in specified health-related areas. |
Physiology of Visual Cortical Neurons in Vitro |
0.943 |
1993 — 2011 |
Hirsch, Judith A |
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. R29Activity Code Description: Undocumented code - click on the grant title for more information. |
Dynamic Properties of Visual Cortical Circuits @ University of Southern California
DESCRIPTION (Adapted From The Applicant's Abstract): How does the synaptic physiology of the cortical microcircuit regulate signal detection in striate cortical neurons? To approach this broad issue we analyze the synaptic basis of neuronal response structures at successive cortical stages and the connections that convey information from one cortical level to the next. The work is made possible by the advance of whole-cell recording in vivo, a technique that gives a highly resolved view of the postsynaptic events evoked during vision and allows intracellular staining of single neurons. AIM 1) The push-pull model of the simple receptive field holds that signals of reverse contrast have the opposite effect: bright stimuli presented to an on subregion evoke firing, whereas dark ones reduce activity. Two mechanisms have been proposed to account for the pull. One is passive withdrawal of excitation from the thalamus; the other is pharmacological analyses of the visual response. Further, we will determine if the push-pull model fully accounts for the spatial distribution of excitation and inhibition in the simple receptive field and if it predicts orientation tuning. AIM 2) Why do many complex cells respond poorly to the same stimuli that drive simple cells well? Our hypothesis is that the successive cortical stages employ different sets of synaptic mechanisms to regulate stimulus selectivity. If true, then complex cells that receive direct thalamic input should have response structures different from those of cells outside thalamic reach. This prediction is tested by comparing responses of cells in layer 4 with those in layer 2+3 to the same stereotyped stimulus. The anatomical substrate for information transfer from the first to second cortical stage is determined by labeling the connections extending from layer 4 to 2+3. A knowledge of how the brain operates in the everyday situation provides a standard against which to judge changes that occur in the course of various disorders, as well as a model system on which to test drugs developed to treat illness. From this perspective, the visual cortex is an obvious site to study; its function and anatomy are better resolved than any other cortical region. A deeper understanding of cortical synaptic mechanisms provides insight into processes that go awry during disease. For example, the work proposed here bears directly on a central theme in research on amblyopia, the examination of how abnormal visual experience leads to changes in central processing.
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1 |
2004 — 2008 |
Hirsch, Judith A |
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. |
Dynamic Properties of Visual Cortical Cirucits @ University of Southern California
[unreadable] DESCRIPTION (provided by applicant): The main route from the retina to the visual cortex is through the lateral geniculate nucleus of the thalamus. While retinal input drives thalamic relay cells to fire and outlines their receptive fields, as yet undefined suppressive mechanisms in the thalamus play critical roles in shaping the signals that ultimately reach cortex. Here we explore directly the means by which two separate inhibitory circuits in the thalamus, one intrinsic to the lateral geniculate and the other originating in the adjacent perigeniculate nucleus, influence spatial and temporal integration within the relay cell's receptive field. Our main approach is whole-cell recording in vivo, which allows us to measure synaptic inhibition directly as well as to identify the neurons whose responses we record as X or Y relay cells or interneurons. (1) The receptive fields of thalamic relay cells inherit their center-surround structure from the retina, whose output is purely excitatory. In the retinal center and surround, stimuli of the reverse contrast evoke intracellular responses of the opposite sign -"push-pull". Is the excitatory (push) structure of the thalamic receptive field routinely matched by inhibition (pull) provided by local interneurons? How do these excitatory and inhibitory inputs interact to shape the information transmitted to cortex? (2) Stimuli presented beyond the classical receptive field, that is, the region bounded by retinal input, have a suppressive effect. Spatially diffuse suppression from this "extra surround" is thought to originate in the perigeniculate nucleus. It will be possible to study the influence of the perigeniculate on relay cells selectively because most neurons there are binocular, thus, permitting stimulation via the non-dominant eye. (3) Diversity in response timing in thalamus is far greater than in retina--a feature central to models of cortical direction selectivity. Current theory holds that the novel delays in excitatory responses result from same-sign inhibition. We will ask whether or not the temporal envelopes of inhibition provided by thalamic interneurons are capable of producing the observed delays in excitation. Knowledge of how the brain operates normally provides a standard against which to judge changes that result from various disorders, as well as a model system on which to test drugs developed to treat illness. From this perspective, the visual thalamus is an obvious site to study; its function and anatomy are better resolved than any other thalamic region. A deeper understanding of local synaptic mechanisms provides insight into processes that go awry during disease. For example, the work proposed here bears directly on a central theme in research on amblyopia, the examination of how abnormal visual experience leads to changes in central processing. [unreadable] [unreadable]
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2007 — 2009 |
Hirsch, Judith |
N/AActivity Code Description: No activity code was retrieved: click on the grant title for more information |
Sger Collaborative Research: Crcns Data Sharing of Intracellular Recordings From the Neocortex @ University of Southern California
Proposal No: 0749032 PI: Judith A. Hirsch
Award Abstract:
This award supports the preparation and sharing of computational neuroscience data as part of an exploratory activity aimed at catalyzing rapid and innovative advances in computational neuroscience and related fields. The data to be shared in this project are intracellular (whole-cell patch) recordings obtained in vivo from visual, auditory, somatosensory, and motor areas of the neocortex by the laboratories of Judith Hirsch, Anthony Zador, Michael DeWeese, and Michael Brecht. These data include not only spikes but also membrane voltages or currents generated by synaptic connections and intrinsic membrane channels. In addition to providing data, the investigators will develop tutorial materials describing recording methods, stimulus paradigms, and issues relevant to the interpretation of intracellular recordings. It is anticipated that this pooled data set will be useful for those wishing to study a particular sensory modality as well as those who hope to understand common features of neocortical function. It will also be of great value for the development of new methods of data analysis.
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0.915 |
2013 — 2021 |
Hirsch, Judith A |
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. |
Neural Circuits That Process Visual Information @ University of Southern California
DESCRIPTION (provided by applicant): Two powerful inhibitory networks in the visual thalamus converge on relay cells and influence every spike that travels downstream. Local interneurons provide feedforward inhibition to relay cells and each other. The thalamic reticular nucleus receives input from relay cells and inhibits them in return. Work in fixed tissue or brain slices has provided insight into the pharmacology, cellular physiology and anatomy of these circuits. It is patently necessary apply these ex vivo results to function in vivo. To bridge this gap, we record from inhibitory cells directly and monitor the inhibition they generate in relay cels during vision. Our strategy updates classical comparative anatomical and physiological approaches by combining whole-cell recording and intracellular labeling in vivo with theory and computational techniques. Aim 1) Exploring the integration of On and Off pathways in the LGN. Relay cells have receptive fields made of concentric On and Off subregions with a push-pull layout of excitation and inhibition; e.g. where bright stimuli excite, dark inhibit. Retina supplie the push (excitation). We propose that the pull (inhibition to stimuli of the reverse sign) comes from local interneurons with receptive fields like those of their postsynaptic partners, but with te opposite preference for stimulus polarity. It is difficult, however, to map connectivity between and On and OFF cells because these cannot be anatomically distinguished in most mammals. Thus, we will test our hypothesis by using the ferret, where On and Off cells occupy different sublaminae in the LGN. Aim 2) Model systems to explore inhibitory mechanisms in higher animals. Genetic approaches make rodent a popular subject for studying vision. However, the cortical organization of carnivore vs. rodent is vastly different, from the level of the functional architecture to properties of single cells. We ask where these differences emerge by quantitatively comparing the synaptic structure of receptive fields in carnivore vs. rodent LGN. Preliminary studies suggest that basic principles of processing in the LGN are conserved. Thus, we will probe push-pull using mutants lacking an On channel. Further, interneurons and relay cells in cat process their inputs in quantitatively different ways that optimize information transmission; we will dissect the bases for these differences in rodent. Aim 3) Inhibitory contributions to processing stimulus contrast. We hypothesize that push-pull and same-sign inhibition (inhibition to the preferred stimulus polarity) expand the range of sensitivity to stimuus contrast and improve feature detection at high contrasts. We will explore extra-retinal mechanisms of contrast gain by comparing retinal input to thalamic output patterns in relay cells and by recording from interneurons. Push- pull vs. same-sign inhibition will be separated empirically by silencing the On channel, and computationally with conductance based models. In addition, we will ask how inhibition contributes to feature selectivity by assessing changes in the relative weights of push and pull at different contrasts.
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