Joshua Gordon, M.D., Ph.D.
Integrative Neuroscience Section
Building 35, Room 1C-905
35 Convent Drive
Bethesda, MD 20892
Working memory, the storing of behaviorally relevant information on a timescale of seconds, is a central component of cognition. Working memory deficits also feature prominently in many psychiatric disorders, including schizophrenia. Complex networks of neurons across the brain appear to work in concert to produce normal working memory. Dysfunction of this cognitive domain in schizophrenia may therefore arise from the widespread neural circuit dysconnectivity observed in patients with, and models of, this disorder. Importantly, however, the neural computations that give rise to normal and disordered working memory function, and the micro- and macro-circuits of neurons that subserve these computations, are largely unknown.
In the Integrative Neuroscience Section (INS), there are two principal goals:  probe the neural circuit basis of normal working memory; and  characterize the neural circuit and working memory dysfunction in mouse models of genetic susceptibility to schizophrenia and related disorders to both understand their pathophysiology and identify novel treatment targets. The section uses in vivo electrophysiology and other neural circuit tools (e.g. in vivo fiber photometry, fluorescence imaging) to record the function of discrete cells and circuits in freely moving animals, and use optogenetic tools to control this function in real-time during behavior. The work focuses on the neural computations within, and circuit-level interactions between, the prefrontal cortex, hippocampus, thalamus, and amygdala. The section also aims to identify molecular targets that influence connectivity within and between these structures, and plasticity mechanisms that may be leveraged to counteract circuit dysconnectivity in psychiatric disease-related models.
Canetta S, Teboul E, Holt E, Bolkan SS, Padilla-Coreano N, Gordon JA, Harrison NL, Kellendonk C. Differential Synaptic Dynamics and Circuit Connectivity of Hippocampal and Thalamic Inputs to the Prefrontal Cortex. Cereb Cortex Commun. 2020;1(1):tgaa084.
Lowes DC, Chamberlin LA, Kretsge LN, Holt ES, Abbas AI, Park AJ, Yusufova L, Bretton ZH, Firdous A, Enikolopov AG, Gordon JA, Harris AZ. Ventral tegmental area GABA neurons mediate stress-induced blunted reward-seeking in mice. Nat Commun. 2021;12(1):3539.
Park AJ, Harris AZ, Martyniuk KM, Chang CY, Abbas AI, Lowes DC, Kellendonk C, Gogos JA, Gordon JA. Reset of hippocampal-prefrontal circuitry facilitates learning. Nature. 2021;591(7851):615-619.
Donegan ML, Stefanini F, Meira T, Gordon JA, Fusi S, Siegelbaum SA. Coding of social novelty in the hippocampal CA2 region and its disruption and rescue in a 22q11.2 microdeletion mouse model. Nat Neurosci. 2020;23(11):1365-1375.
Abbas AI, Sundiang MJM, Henoch B, Morton MP, Bolkan SS, Park AJ, Harris AZ, Kellendonk C, Gordon JA. Somatostatin Interneurons Facilitate Hippocampal-Prefrontal Synchrony and Prefrontal Spatial Encoding. Neuron. 2018;100(4):926-939.e3.
Related Scientific Focus Areas
Genetics and Genomics
This page was last updated on August 25th, 2021