The proposed research will investigate the cortical circuit mechanisms of visual categorization, the process of learning to classify visual stimuli into groups of objects that are equivalent in terms of their behavioral significance. Previous work revealed that individual neurons in the prefrontal cortex (PFC) and the lateral interparietal (LIP) area encode the category membership of stimuli during visual categorization tasks. Built on these findings, we will combine biophysically-realistic neural modeling and single-unit recording from behaving monkeys, to elucidate the mechanistic questions concerning category learning and category-based behavior. First, we will develop a spiking network model of the reciprocally interacting sensory circuit and parieto-prefrontal circuit, to elucidate the cortical basis of key neural computations underlying a delayed match-to-category (DMC) task (do the attributes of a sample and a test stimulus belong to the same category?) versus delayed match-to-sample (DMS) task (are the attributes of the sample and test identical?). Second, we will examine how categories are learnt through discrete training stages, from identity-based match-to-sample to fine category discrimination with stimuli near an arbitrary category boundary. This will be done using models endowed with reward-dependent synaptic learning, monkey behavioral assessment and single-unit recordings from monkeys at different stages of training. Third, we will examine task switching, on a trial-by-trial basis, between the identity-based DMS versus category-based DMC, to clarify the differential neural coding of stimulus identity and category, as well as task-rule representation in visual categorization, in the LIP and PFC. Together, these studies will shed important insights and yield a computational framework for understanding how the brain encodes the learned significance, or category membership, of visual stimuli. Intellectual Merits: Without the ability to classify or categorize stimuli, it would be difficult to perceive and comprehend the world;concepts and language would seem impossible. Therefore, elucidating the neural mechanisms of categorization is a crucial step in our quest for a neurobiological understanding of higher cognition. While much is known about how the brain processes sensory attributes (such as orientation and direction of motion), much less is known about how the brain achieves more abstract knowledge acquisition such as how attributes are grouped into categories through learning, and what are the computational advantages of category-based behavior. A mechanistic understanding of these issues, at the neural circuit level, necessitates a concerted computational and experimental effort. Thus, the results of our proposed research program are likely to represent a significant advance in this area, with broad implications. Our highly promising preliminary computational, behavioral and neuronal studies have validated our approach, and have ensured that all aspects of this project have a high likelihood of success. Broader Impacts and Integration of Education and Research Activities: Both PIs are actively involved with teaching. Dr. Wang teaches for the Interdepartmental Neuroscience graduate program and for the new Physics/Engineering/Biology (PEB) integrated graduate program at Yale. Dr Freedman is preparing new workshop course called """"""""Methods in neuronal data analysis"""""""" to both graduate and undergraduate students. Lessons and exercises will revolve around computational and statistical analysis of real data collected in his laboratory during the experiments proposed here. Dr Wang is a member of the Oversight Committee for Description Standards in Neural Network Modeling, International Neuroinformatics Coordinating Facility (INCF). Models developed in his lab will be made available to the computational community. Broaden Participation of under-represented groups-Both PI have a strong track record of recruiting and mentoring students from under-represented groups. At this time, Dr. Wang has a female graduate student and a female postdoctoral fellow (Dr Tatiana Engel who will spearhead the proposed research in his laboratory). Over the past two years four graduate students in Dr. Freedman's laboratory are from underrepresented groups (one is African American and the others are women). Outreach to general public- Both PIs have been active in outreach. Dr Wang has given lectures on the brain at the Hopkins School in New Haven;Dr Freedman has been involved in the """"""""Science and Technology Outreach and Mentoring Program"""""""", """"""""The Young Scientist Training Program"""""""", and the student science fair at Kenwood Academy public school, in Chicago. Our work focuses on the brain mechanisms of learning and memory, a topic which is both accessible and of great interest to the general public. For our outreach and mentorship efforts, we will use data generated during the proposed work to produce educational demonstrations of how the brain learns and processes visual information that will be accessible to a lay audience. These demonstrations will be used in K-12 classroom presentations and also available online.

National Institute of Health (NIH)
National Institute of Mental Health (NIMH)
Research Project (R01)
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Special Emphasis Panel (ZRG1-IFCN-B (51))
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Glanzman, Dennis L
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New York University
Schools of Arts and Sciences
New York
United States
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Masse, Nicolas Y; Grant, Gregory D; Freedman, David J (2018) Alleviating catastrophic forgetting using context-dependent gating and synaptic stabilization. Proc Natl Acad Sci U S A 115:E10467-E10475
Chaisangmongkon, Warasinee; Swaminathan, Sruthi K; Freedman, David J et al. (2017) Computing by Robust Transience: How the Fronto-Parietal Network Performs Sequential, Category-Based Decisions. Neuron 93:1504-1517.e4
Masse, Nicolas Y; Hodnefield, Jonathan M; Freedman, David J (2017) Mnemonic Encoding and Cortical Organization in Parietal and Prefrontal Cortices. J Neurosci 37:6098-6112
Sarma, Arup; Masse, Nicolas Y; Wang, Xiao-Jing et al. (2016) Task-specific versus generalized mnemonic representations in parietal and prefrontal cortices. Nat Neurosci 19:143-9
Wei, Wei; Wang, Xiao-Jing (2016) Inhibitory Control in the Cortico-Basal Ganglia-Thalamocortical Loop: Complex Regulation and Interplay with Memory and Decision Processes. Neuron 92:1093-1105
Engel, Tatiana A; Chaisangmongkon, Warasinee; Freedman, David J et al. (2015) Choice-correlated activity fluctuations underlie learning of neuronal category representation. Nat Commun 6:6454
Engel, Tatiana A; Wang, Xiao-Jing (2011) Same or different? A neural circuit mechanism of similarity-based pattern match decision making. J Neurosci 31:6982-96