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. ? ?

Agency
National Institute of Health (NIH)
Institute
National Eye Institute (NEI)
Type
Research Project (R01)
Project #
5R01EY009593-16
Application #
7442100
Study Section
Central Visual Processing Study Section (CVP)
Program Officer
Oberdorfer, Michael
Project Start
1993-07-01
Project End
2009-09-29
Budget Start
2008-07-01
Budget End
2009-09-29
Support Year
16
Fiscal Year
2008
Total Cost
$349,003
Indirect Cost
Name
University of Southern California
Department
Biology
Type
Schools of Arts and Sciences
DUNS #
072933393
City
Los Angeles
State
CA
Country
United States
Zip Code
90089
Suresh, Vandana; Çiftçio?lu, Ula? M; Wang, Xin et al. (2016) Synaptic Contributions to Receptive Field Structure and Response Properties in the Rodent Lateral Geniculate Nucleus of the Thalamus. J Neurosci 36:10949-10963
Hirsch, Judith A; Wang, Xin; Sommer, Friedrich T et al. (2015) How inhibitory circuits in the thalamus serve vision. Annu Rev Neurosci 38:309-29
Martinez, Luis M; Molano-Mazón, Manuel; Wang, Xin et al. (2014) Statistical wiring of thalamic receptive fields optimizes spatial sampling of the retinal image. Neuron 81:943-956
Wang, Xin; Sommer, Friedrich T; Hirsch, Judith A (2011) Inhibitory circuits for visual processing in thalamus. Curr Opin Neurobiol 21:726-33
Wang, Xin; Vaingankar, Vishal; Soto Sanchez, Cristina et al. (2011) Thalamic interneurons and relay cells use complementary synaptic mechanisms for visual processing. Nat Neurosci 14:224-31
Koepsell, Kilian; Wang, Xin; Hirsch, Judith A et al. (2010) Exploring the function of neural oscillations in early sensory systems. Front Neurosci 4:53
Wang, Xin; Hirsch, Judith A; Sommer, Friedrich T (2010) Recoding of sensory information across the retinothalamic synapse. J Neurosci 30:13567-77
Koepsell, Kilian; Wang, Xin; Vaingankar, Vishal et al. (2009) Retinal oscillations carry visual information to cortex. Front Syst Neurosci 3:4
Stepanyants, Armen; Martinez, Luis M; Ferecsko, Alex S et al. (2009) The fractions of short- and long-range connections in the visual cortex. Proc Natl Acad Sci U S A 106:3555-60
Wang, Xin; Wei, Yichun; Vaingankar, Vishal et al. (2007) Feedforward excitation and inhibition evoke dual modes of firing in the cat's visual thalamus during naturalistic viewing. Neuron 55:465-78

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