Speaker 3: John Krystal, USA

s | 5 different parvalbumin-expressing basket cells fired preferentially at different episodes during the task (e.g. stimulus, delay, execution). A difference in the firing of parvalbumin-expressing basket cells according to the decisions was observed often only after its execution and during or shortly after reward consumption. Thus, parvalbumin-expressing basket cells support the encoding of temporal sequences and distinct task episodes during working memory and decision making. We have developed a novel technique that allows the recording of unequivocally identified neurons and show how distinct types of neuron contribute to prefrontal network operations and executive behavior. Our results indicate that GABAergic interneurons release GABA at distinct times to different domains of pyramidal cells contributing to the formation of cell assemblies and representations in the prefrontal cortex. Speaker 3: John Krystal, USA Title: Cortical disinhibition, noisy circuits, and schizophrenia: clinical and therapeutic implications. John H. Krystal, M.D. (1), Alan Anticevic, Ph.D. (1), Genevieve Yang (1), Naomi Driesen, Ph.D. (1), Jose Cortes-Briones, Ph.D. (1), James M. Stone, MBBS. (2), Xiao-Jing Wang, Ph.D. (3), John D. Murray, Ph.D. (1) (1) Departments of Psychiatry, Neuroscience, and Psychology, Yale University, New Haven, CT USA; (2) Institute of Psychiatry, Psychology, and Neuroscience, Kings College, London, UK; (3) Center for Neural Science, New York University, New York, NY USA Abstract It is not yet clear how the molecular and cellular alterations identified in post-mortem tissue from individuals diagnosed with schizophrenia translate into the disabling symptoms and cognitive impairments associated with this disorder. Approach: The purpose of this presentation is to present results from a series of fMRI and EEG studies evaluating healthy individuals, schizophrenia patients, and healthy individuals administered the NMDA-R antagonist, ketamine that have been analyzed and interpreted within the context of parallel studies employing biophysically-informed computational neuroscience models of the behavior of cortical microcircuits and macrocircuits. Results: Three types of network disinhibiton are described: 1) gross disinhibition, “hyperactivity” that is associated withIt is not yet clear how the molecular and cellular alterations identified in post-mortem tissue from individuals diagnosed with schizophrenia translate into the disabling symptoms and cognitive impairments associated with this disorder. Approach: The purpose of this presentation is to present results from a series of fMRI and EEG studies evaluating healthy individuals, schizophrenia patients, and healthy individuals administered the NMDA-R antagonist, ketamine that have been analyzed and interpreted within the context of parallel studies employing biophysically-informed computational neuroscience models of the behavior of cortical microcircuits and macrocircuits. Results: Three types of network disinhibiton are described: 1) gross disinhibition, “hyperactivity” that is associated with symptoms of psychosis, 2) disinhibition of the spatial dispersion of activation resulting in impairment in sparse coding of information, reduced memory precision, increased cortical signal variance “noise”, and the emergence of “false” memories, and 3) disinhibition of suppressed inputs, resulting in pathological hyperconnectivity. We will show evidence that the progression of schizophrenia is associated with altered signal properties of cortical functional connectivity, potentially creating the opportunity for illness phase-specific pharmacotherapies for this disorder.