The mammalian neocortex mediates a variety of cognitive functions, and understanding the circuit basis for cortical processing is a central goal in neuroscience. In the primary visual cortex (V1), the receptive field properties of individual neurons have been characterized extensively, but the underlying neuronal circuitry remains unclear. The goal of the proposed research is to dissect the excitatory and inhibitory synaptic inputs underlying the spatiotemporal receptive fields of V1 neurons. Experimentally, we will make intracellular (patch clamp) recordings in anesthetized rats and cats to measure the synaptic inputs to cortical neurons. Computationally, we will apply both linear and nonlinear analyses to determine the receptive field properties of each input. There are four specific aims.
Aim 1 is to characterize the synaptic mechanisms underlying the basic receptive field and direction selectivity of simple cells. To test the anti-phase inhibition model, we will determine the extent to which the excitatory and inhibitory receptive fields are matched to each other with opposite ON/OFF polarities. The contributions of several proposed mechanisms to simple cell direction selectivity will be assessed.
Aim 2 is to characterize the synaptic circuitry underlying the receptive field subunits of complex cells. The predictions of different circuit models for complex cell RFs will be tested. We will also determine the contributions of several proposed mechanisms to complex cell direction selectivity.
In Aims 3 and 4 we will address two of the more advanced receptive field properties involved in processing motion stimuli. Our recent study using extracellular recordings indicated a spatial asymmetry in direction-selective inputs to V1 neurons, which gives rise to two novel RF properties that could account for two visual illusions.
In Aim 3, we will examine the spatial distributions of direction-selective excitatory and inhibitory inputs in order to test and constrain the asymmetric circuit model.
In Aim 4, we will measure the effects of motion adaptation on the strength and direction selectivity of excitatory and inhibitory synaptic input to determine how these inputs contribute to adaptation-induced change in V1 direction selectivity. To further test the asymmetric circuit model, we will also measure the effect of motion adaptation on the spatial distributions of the excitatory and inhibitory inputs. Such comprehensive characterization of the synaptic mechanisms underlying cortical receptive field properties is not only crucial for understanding V1 functions, but also likely to shed light on the general principles of cortical computation.

Public Health Relevance

Balance between excitation and inhibition in the cortex is critical for normal brain functions, and disruption of the balance causes a variety of mental disorders. The proposed research aims to understand the relationship between excitatory and inhibitory inputs, and how they shape the functional properties of visual cortical neurons. Such knowledge will be crucial for the development of treatment for not only deficiencies in visual functions, but also other neurological disorders such as epilepsy.

Agency
National Institute of Health (NIH)
Institute
National Eye Institute (NEI)
Type
Research Project (R01)
Project #
5R01EY018861-02
Application #
7635752
Study Section
Cognitive Neuroscience Study Section (COG)
Program Officer
Steinmetz, Michael A
Project Start
2008-07-01
Project End
2013-06-30
Budget Start
2009-07-01
Budget End
2010-06-30
Support Year
2
Fiscal Year
2009
Total Cost
$370,767
Indirect Cost
Name
University of California Berkeley
Department
Neurosciences
Type
Organized Research Units
DUNS #
124726725
City
Berkeley
State
CA
Country
United States
Zip Code
94704
Kamigaki, Tsukasa; Dan, Yang (2017) Delay activity of specific prefrontal interneuron subtypes modulates memory-guided behavior. Nat Neurosci 20:854-863
Minces, Victor; Pinto, Lucas; Dan, Yang et al. (2017) Cholinergic shaping of neural correlations. Proc Natl Acad Sci U S A 114:5725-5730
Zhang, Siyu; Xu, Min; Chang, Wei-Cheng et al. (2016) Organization of long-range inputs and outputs of frontal cortex for top-down control. Nat Neurosci 19:1733-1742
Bochner, David N; Sapp, Richard W; Adelson, Jaimie D et al. (2014) Blocking PirB up-regulates spines and functional synapses to unlock visual cortical plasticity and facilitate recovery from amblyopia. Sci Transl Med 6:258ra140
Zhang, Siyu; Xu, Min; Kamigaki, Tsukasa et al. (2014) Selective attention. Long-range and local circuits for top-down modulation of visual cortex processing. Science 345:660-5
Pinto, Lucas; Goard, Michael J; Estandian, Daniel et al. (2013) Fast modulation of visual perception by basal forebrain cholinergic neurons. Nat Neurosci 16:1857-1863
Kwan, Alex C; Dan, Yang (2012) Dissection of cortical microcircuits by single-neuron stimulation in vivo. Curr Biol 22:1459-67
Lee, Seung-Hee; Kwan, Alex C; Zhang, Siyu et al. (2012) Activation of specific interneurons improves V1 feature selectivity and visual perception. Nature 488:379-83
Li, Ye; Lu, Hui; Cheng, Pei-lin et al. (2012) Clonally related visual cortical neurons show similar stimulus feature selectivity. Nature 486:118-21
Hang, Giao B; Dan, Yang (2011) Asymmetric temporal integration of layer 4 and layer 2/3 inputs in visual cortex. J Neurophysiol 105:347-55

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