In the proposed research, we will use a newly developed primate optogenetic tool, which enables us to create reversible """"""""micro lesions"""""""" within the neocortex of awake, behaving monkeys. Using this tool, we will test and quantify the role of macaque Area V4, an intermediate stage of processing within the ventral visual processing stream.
In Aim 1, we will examine how this new tool modulates the gain of neuronal responses, and will quantify the region of activation as a function of illumination level. Area V4 has a patchy organization, with some regions being selective for color, and others selective for orientation.
In Aim 2, we will test the role of V4 in the perception of color and of orientation, by having monkeys make fine discriminations of color and orientation, while we inactivate patches color- or orientation-selective neurons. We will examine whether activating the neurons tuned for color impairs color judgments, and not orientation judgments, and whether activating the neurons tuned for orientation impairs orientation judgments, and not color judgments. We will also examine whether this impairment is greater when we inactivate neurons tuned for the discriminanda or, alternatively, tuned such that the steep part of the tuning curve is suited to discriminate among discriminanda.
In Aim 3, we will use optogenetic micro lesions to test whether V4 plays a causal role in mediating attentional selection. The data we collect will provide the most direct evidence for or against the proposition that V4 plays a causal role in the perception of color and of orientation, and whether it plays a causal role in attentional selection. In addition, the proposed research will demonstrate the use of this new optogenetic tool, and we will make it publicly available, so that other researchers working in primates and in other species, can use this tool to test theories of perception, cognition and action.

Public Health Relevance

In order to help people with brain disorders that impair perception and attention like neglect, schizophrenia, ADHD and autism, we need to understand how the neural mechanisms that mediate these functions normally work. To study this, we have developed and implemented a new type of tool that enables us to cause neurons to sprout microscopic light sensors that temporarily turn off their parent neuron when they are illuminated by blue light. The proposed research will use this new tool to briefly turn off the activity of neurons in a part of the brain that is thought to be involved in perception and attention, enabling us to test theories about how it normally operates and how it fails in brain disorders.

Agency
National Institute of Health (NIH)
Institute
National Eye Institute (NEI)
Type
Research Project (R01)
Project #
5R01EY021827-02
Application #
8320103
Study Section
Special Emphasis Panel (ZRG1-IFCN-C (03))
Program Officer
Steinmetz, Michael A
Project Start
2011-09-01
Project End
2016-08-31
Budget Start
2012-09-01
Budget End
2013-08-31
Support Year
2
Fiscal Year
2012
Total Cost
$476,250
Indirect Cost
$226,250
Name
Salk Institute for Biological Studies
Department
Type
DUNS #
078731668
City
La Jolla
State
CA
Country
United States
Zip Code
92037
Nandy, Anirvan S; Nassi, Jonathan J; Reynolds, John H (2017) Laminar Organization of Attentional Modulation in Macaque Visual Area V4. Neuron 93:235-246
Nandy, Anirvan S; Mitchell, Jude F; Jadi, Monika P et al. (2016) Neurons in Macaque Area V4 Are Tuned for Complex Spatio-Temporal Patterns. Neuron 91:920-930
Izpisua Belmonte, Juan Carlos; Callaway, Edward M; Caddick, Sarah J et al. (2015) Brains, genes, and primates. Neuron 86:617-31
Nassi, Jonathan J; Avery, Michael C; Cetin, Ali H et al. (2015) Optogenetic Activation of Normalization in Alert Macaque Visual Cortex. Neuron 86:1504-17
Disney, Anita A; McKinney, Collin; Grissom, Larry et al. (2015) A multi-site array for combined local electrochemistry and electrophysiology in the non-human primate brain. J Neurosci Methods 255:29-37
Disney, Anita A; Alasady, Hussein A; Reynolds, John H (2014) Muscarinic acetylcholine receptors are expressed by most parvalbumin-immunoreactive neurons in area MT of the macaque. Brain Behav 4:431-45
Disney, Anita A; Reynolds, John H (2014) Expression of m1-type muscarinic acetylcholine receptors by parvalbumin-immunoreactive neurons in the primary visual cortex: a comparative study of rat, guinea pig, ferret, macaque, and human. J Comp Neurol 522:986-1003
Ruiz, Octavio; Lustig, Brian R; Nassi, Jonathan J et al. (2013) Optogenetics through windows on the brain in the nonhuman primate. J Neurophysiol 110:1455-67