NEUROPHYSIOLOGY UNDERLYING NEURAL REPRESENTATIONS OF VALUE
C Daniel Salzman
Columbia University Health Sciences, Columbia University Medical Center, New York, Ny 10032-3702
Grant 3R01MH082017-03S1 from National Institute Of Mental Health
Abstract: This project seeks to elucidate how the brain can form predictions about impending reinforcement in a variety of behavioral contexts and learning paradigms, which is a fundamental goal in neuroscience. The project involves obtaining neurophysiological recordings in the amygdala and OFC simultaneously so that one can understand the relationship and timing of activity between the two brain areas. Recent work from the Salzman lab has shown that the amygdala provides a representation of the positive or negative value of visual stimuli during a classical conditioning procedure in which there is a one-to-one mapping between a sensory stimulus and a particular reinforcement outcome. This proposal involves extending this recent work to now examine simultaneously the interrelated neurophysiology of the amygdala and orbitofrontal cortex (OFC) during both simple and more complex forms of reinforcement learning. The amygdala and OFC are central nodes in neural circuitry commonly assumed to link sensory stimuli with affective values so as to drive adaptive cognitive, behavioral, and physiological responses. Dysfunction of these neural circuits likely plays a role in many psychiatric diseases, such as mood, anxiety, addictive and other disorders. The first aim examines amygdala and OFC single neuron activity local field potentials (LFPs) during learning induced by classical conditioning in order to understand the physiological properties and relative timing dynamics of activity in the two brain areas. The second aim extends this work by studying the physiology of these brain areas in conditions when motivationally significant stimuli have different meanings depending on the moment-to-moment context in which they are presented. If neural processing in the amygdala and OFC can switch rapidly as the value of a stimulus changes from trial to trial depending upon a contextual cue, it will indicate that rapid context-dependent mechanisms can facilitate the switching between representations of value. The third aim investigates whether neurons in the amygdala and OFC represent the ?absolute? or the ?relative? value of conditioned stimuli by using a reinforcer revaluation paradigm that manipulates the relative value of a stimulus but holds constant its absolute value. This task requires the integration of information about the overall context of the task in order to judge the relative value of a particular stimulus. For both the second and third aims, we hypothesize that OFC either encodes contextual information about a stimulus (Aim 2), or integrates information about an overall task context (Aim 3) in part to help govern and update neural representations of value. In this scenario, OFC would be part of a cortical mechanism that integrates high-level information in order to help control neural representations of value and the emotional processes that are based on such representations
Keywords: Accounting; Affective; Air; Amygdala; Amygdaloid Body; Amygdaloid Nucleus; Amygdaloid structure; Animals; Anxiety; Appearance; Area; Association Learning; Associative Learning; Aversive Stimulus; Behavior; Behavioral; Blinking; Brain; Cell Communication and Signaling; Cell Signaling; Cognitive; Complex; Conditioning, Classical; Conditionings, Classical; Cues; Data; Disease; Disorder; Doctor of Medicine; Doctor of Philosophy; Dysfunction; Emotional; Encephalon; Encephalons; Environment; Face; Functional disorder; Future; Goals; Human; Human, General; Individual; Intracellular Communication and Signaling; Learning; Link; Liquid substance; M.D.; Mammals, Primates; Man (Taxonomy); Man, Modern; Maps; Measures; Mental disorders; Mental health disorders; Monkeys; Moods; Nerve Cells; Nerve Unit; Nervous; Nervous System, Brain; Neural Cell; Neurocyte; Neurons; Neurosciences; Organism; Outcome; Pavlovian conditioning; Ph.D.; PhD; Physiologic; Physiological; Physiology; Physiopathology; Play; Population; Primates; Procedures; Process; Property; Property, LOINC Axis 2; Psychiatric Disease; Psychiatric Disorder; Psychological reinforcement; Punishment; Regulation; Reinforcement; Reinforcement (Psychology); Relative; Relative (related person); Research; Reversal Learning; Rewards; Role; Science of neurophysiology; Sensory; Signal Transduction; Signal Transduction Systems; Signaling; Stimulus; Structure; Testing; Time; Unspecified Mental Disorder; Update; Visual; Work; amygdaloid nuclear complex; base; biological signal transduction; classical conditioning; conditioning; disease/disorder; experience; eye blink; eyeblink; facial; flexibility; fluid; liquid; living system; mental illness; neural; neural circuit; neural circuitry; neural control; neural regulation; neuronal; neurophysiology; neuroregulation; pathophysiology; perceptual stimulus; physicochemical phenomena related to the senses; psychological disorder; reinforcer; relating to nervous system; response; sensory stimulus; social role; visual stimulus
Project start date: 2010-03-01
Project end date: 2011-02-28
Budget start date: 1-MAR-2010
Budget end date: 28-FEB-2011
PFA/PA: PA-07-070
3R01MH082017-03S1 (2010): $167784
Sponsored Links Excellgen http://Excellgen.com
Grants awarded to C Daniel Salzman
ELUCIDATION OF PREFRONTAL-AMYGDALA NEURAL CIRCUITRY WITH OPTOGENETIC TECHNIQUES
C Daniel Salzman
Columbia University Health Sciences, Columbia University Medical Center, New York, Ny 10032-3702
Grant 5RC1MH088458-02 from National Institute Of Mental Health
Abstract: This proposal addresses broad Challenge Area (15) Translational Science, and specific challenge topic 15-MH-109 Prefrontal cortex regulation of higher brain function and complex behaviors. Nearly all psychiatric disorders, from schizophrenia to depression to addiction, disrupt emotional processing. A key aspect of the pathophysiology underlying these psychiatric disorders is thought to lie in the dysfunction of the pre-frontal cortex, especially with respect to the manner by which the pre-frontal cortex regulates emotions. We focus in this proposal on the interactions between the pre-frontal cortex and the amygdala, a key coordinator of emotional behavior. This circuitry has been highlighted as being critical for controlling emotional responses. Our lab has recently shown that neurons in the primate amygdala respond differentially depending upon whether a cue predicts a reward or an aversive stimulus, with different populations of neurons preferring reward and aversive associations, respectively. More recent preliminary data indicates that this flexible representation of reinforcement contingencies can be "gated" - or updated instantly - depending upon a subject´s learning and applying a rule for interpreting cues accurately. In this proposal, we will test the hypothesis that this gating of neural signals in the amygdala depends critically on input from the orbitofrontal cortex (OFC), a component of the pre-frontal cortex with strong connections to the amygdala. Our approach is to adapt methods for genetically and anatomically targeted expression of channelrhodopsin (ChR2) and halorhodopsin (NpHr) (light-activated channels that can be used to photo-activate or photo-inactivate neurons). These optogenetic techniques will be used in combination with neurophysiological and complex behavioral experiments. We will determine if the flexible physiological properties in the amygdala require pre-frontal input by selectively inactivating pre-frontal input with halorhodopsin, and we will further determine if disrupting information transmission from OFC to the amygdala impacts complex behavior. Overall, the development of these techniques promises to transform the study of pre-frontal/amygdala interactions by elucidating how pre-frontal input can regulate the responsivity of the amygdala, a key mechanism in maintaining normal adaptive emotional responses that likely becomes dysfunctional in many psychiatric disorders. This proposal involves the development of optogenetic techniques for investigating how the prefrontal cortex regulates the amygdala in order to control emotional behavior. Since most psychiatric disorders, including mood and anxiety disorders, schizophrenia, and depression involve dysfunction in these neural circuits, this project promises to lay the groundwork for developing new treatments
Keywords: Achievement; Achievement Attainment; Adaptive Behaviors; Address; Ak-Tate; Amygdala; Amygdaloid Body; Amygdaloid Nucleus; Amygdaloid structure; Animal Model; Animal Models and Related Studies; Anxiety Disorders; Area; Articulose-50; Aversive Stimulus; Balpred; Behavior; Behavioral; Behaviors, Adaptive; Brain; Cell Communication and Signaling; Cell Signaling; Cognitive; Complex; Cues; Data; Deltacortilen; Deltastab; Depression; Development; Diopred; Disease; Disorder; Dysfunction; Econopred; Electrodes, Miniaturized; Emotional; Emotions; Encephalon; Encephalons; Functional disorder; Funding; Goals; Halorhodopsin Chromoprotein; Halorhodopsins; Hexacortone; Histology; Human; Human, General; Hydrocortancyl; Individual; Inf-Oph; Inflanefran; Intracellular Communication and Signaling; Key-Pred; Learning; Locaseptil-Neo; Macaca mulatta; Mammals, Mice; Mammals, Primates; Mammals, Rodents; Man (Taxonomy); Man, Modern; Mental Depression; Mental disorders; Mental health disorders; Methods; Methods and Techniques; Methods, Other; Mice; Microelectrodes; Modeling; Monkeys; Moods; Murine; Mus; Nerve; Nerve Cells; Nerve Unit; Nervous; Nervous System, Brain; Neural Cell; Neurocyte; Neurons; Operation; Operative Procedures; Operative Surgical Procedures; Ophtho-Tate; Pathway interactions; Performance; Physiologic; Physiological; Physiopathology; Population; Pred Fort; Pred Forte; Pred Mild; Predaject; Predalone; Predate; Predcor; Prednefrin SF; Predni-H; Predni-POS; Prednihexal; Predniocil; Prefrontal Cortex; Primates; Process; Property; Property, LOINC Axis 2; Psychiatric Disease; Psychiatric Disorder; Psychological reinforcement; Regulation; Reinforcement; Reinforcement (Psychology); Rewards; Rhesus; Rhesus Macaque; Rhesus Monkey; Rodent; Rodent Model; Rodentia; Rodentias; Role; Schizophrenia; Schizophrenic Disorders; Science of neurophysiology; Signal Transduction; Signal Transduction Systems; Signaling; Stimulus; Structure; Surgical; Surgical Interventions; Surgical Procedure; Techniques; Technology; Testing; Time; Transfection; Translational Research; Translational Research Enterprise; Translational Science; Transmission; Unspecified Mental Disorder; Update; Viral; Virus; Viruses, General; Work; adaptation behavior; adaptive behavior; addiction; amygdaloid nuclear complex; biological signal transduction; brain behavior; dementia praecox; disease/disorder; emotion regulation; experiment; experimental research; experimental study; flexibility; frontal cortex; frontal lobe; mental illness; model organism; neural; neural circuit; neural circuitry; neural mechanism; neuromechanism; neuronal; neurophysiology; neuropsychiatric; neuropsychiatry; pathophysiology; pathway; psychological disorder; public health relevance; relating to nervous system; research study; response; schizophrenic; social role; surgery; technique development; tool; translation research enterprise; transmission process
Relevance: This proposal involves the development of optogenetic techniques for investigating how the prefrontal cortex regulates the amygdala in order to control emotional behavior. Since most psychiatric disorders, including mood and anxiety disorders, schizophrenia, and depression involve dysfunction in these neural circuits, this project promises to lay the groundwork for developing new treatments
Project start date: 2009-09-30
Project end date: 2011-08-31
Budget start date: 1-SEP-2010
Budget end date: 31-AUG-2011
PFA/PA: RFA-OD-09-003
5RC1MH088458-02 (2010): $499999
1RC1MH088458-01 (2009): $499997
NEUROPHYSIOLOGY UNDERLYING NEURAL REPRESENTATIONS OF VALUE
C Daniel Salzman
Columbia University Health Sciences, Columbia University Medical Center, New York, Ny 10032-3702
Grant 5R01MH082017-03 from National Institute Of Mental Health
Abstract: This project seeks to elucidate how the brain can form predictions about impending reinforcement in a variety of behavioral contexts and learning paradigms, which is a fundamental goal in neuroscience. The project involves obtaining neurophysiological recordings in the amygdala and OFC simultaneously so that one can understand the relationship and timing of activity between the two brain areas. Recent work from the Salzman lab has shown that the amygdala provides a representation of the positive or negative value of visual stimuli during a classical conditioning procedure in which there is a one-to-one mapping between a sensory stimulus and a particular reinforcement outcome. This proposal involves extending this recent work to now examine simultaneously the interrelated neurophysiology of the amygdala and orbitofrontal cortex (OFC) during both simple and more complex forms of reinforcement learning. The amygdala and OFC are central nodes in neural circuitry commonly assumed to link sensory stimuli with affective values so as to drive adaptive cognitive, behavioral, and physiological responses. Dysfunction of these neural circuits likely plays a role in many psychiatric diseases, such as mood, anxiety, addictive and other disorders. The first aim examines amygdala and OFC single neuron activity local field potentials (LFPs) during learning induced by classical conditioning in order to understand the physiological properties and relative timing dynamics of activity in the two brain areas. The second aim extends this work by studying the physiology of these brain areas in conditions when motivationally significant stimuli have different meanings depending on the moment-to-moment context in which they are presented. If neural processing in the amygdala and OFC can switch rapidly as the value of a stimulus changes from trial to trial depending upon a contextual cue, it will indicate that rapid context-dependent mechanisms can facilitate the switching between representations of value. The third aim investigates whether neurons in the amygdala and OFC represent the ?absolute? or the ?relative? value of conditioned stimuli by using a reinforcer revaluation paradigm that manipulates the relative value of a stimulus but holds constant its absolute value. This task requires the integration of information about the overall context of the task in order to judge the relative value of a particular stimulus. For both the second and third aims, we hypothesize that OFC either encodes contextual information about a stimulus (Aim 2), or integrates information about an overall task context (Aim 3) in part to help govern and update neural representations of value. In this scenario, OFC would be part of a cortical mechanism that integrates high-level information in order to help control neural representations of value and the emotional processes that are based on such representations
Keywords: Accounting; Affective; Air; Amygdala; Amygdaloid Body; Amygdaloid Nucleus; Amygdaloid structure; Animals; Anxiety; Appearance; Area; Association Learning; Associative Learning; Aversive Stimulus; Behavior; Behavioral; Blinking; Brain; Cell Communication and Signaling; Cell Signaling; Cognitive; Complex; Conditioning, Classical; Conditionings, Classical; Cues; Data; Disease; Disorder; Doctor of Medicine; Doctor of Philosophy; Dysfunction; Emotional; Encephalon; Encephalons; Environment; Face; Functional disorder; Future; Goals; Human; Human, General; Individual; Intracellular Communication and Signaling; Learning; Link; Liquid substance; M.D.; Mammals, Primates; Man (Taxonomy); Man, Modern; Maps; Measures; Mental disorders; Mental health disorders; Monkeys; Moods; Nerve Cells; Nerve Unit; Nervous; Nervous System, Brain; Neural Cell; Neurocyte; Neurons; Neurosciences; Organism; Outcome; Pavlovian conditioning; Ph.D.; PhD; Physiologic; Physiological; Physiology; Physiopathology; Play; Population; Primates; Procedures; Process; Property; Property, LOINC Axis 2; Psychiatric Disease; Psychiatric Disorder; Psychological reinforcement; Punishment; Regulation; Reinforcement; Reinforcement (Psychology); Relative; Relative (related person); Research; Reversal Learning; Rewards; Role; Science of neurophysiology; Sensory; Signal Transduction; Signal Transduction Systems; Signaling; Stimulus; Structure; Testing; Time; Unspecified Mental Disorder; Update; Visual; Work; amygdaloid nuclear complex; base; biological signal transduction; classical conditioning; conditioning; disease/disorder; experience; eye blink; eyeblink; facial; flexibility; fluid; liquid; living system; mental illness; neural; neural circuit; neural circuitry; neural control; neural regulation; neuronal; neurophysiology; neuroregulation; pathophysiology; perceptual stimulus; physicochemical phenomena related to the senses; psychological disorder; reinforcer; relating to nervous system; response; sensory stimulus; social role; visual stimulus
Project start date: 2008-04-10
Project end date: 2013-01-31
Budget start date: 1-FEB-2010
Budget end date: 31-JAN-2011
PFA/PA: PA-07-070
5R01MH082017-03 (2010): $326025
NEURAL CORRELATES OF EMOTIONAL LEARNING AND BEHAVIOR
C Daniel Salzman
Columbia University Health Sciences Columbia University Medical Center New York, Ny 100323702
Grant 5K01MH001724-06 from National Institute Of Mental Health IRG: ZRG1
Abstract: Dysfunction in neural circuits within the limbic system has been implicated in the pathophysiology of many psychiatric diseases, such as mood disorders, anxiety disorders, and schizophrenia. Indeed, psychiatric illness is frequently in part characterized by patients having abnormal emotional, or affective, responses to sensory stimuli, events, and memories. The primary goal of this research program is to study the manner in which sensory stimuli are endowed with affective significance to produce emotional behavior. Within the limbic system, the amygdala appears to play a prominent role in mediating emotional responses to sensory stimuli. The specific aim of this proposal investigates amygdala neural responses to visual stimuli that have acquired affective significance through Pavlovian conditioning in monkeys performing an emotional learning behavioral paradigm. In addition , psychophysiological recordings will be obtained during task measurements of psychophysiological parameters. In this manner, neural correlates of emotional learning and behavior will be sought. The second specific aim of this proposal involves recording the activity of neurons in area TE of inferotemporal cortex while monkeys perform the same emotional learning paradigm. Again, psychophysiological recordings will be obtained simultaneous to the neurophysiological recordings. Area TE is the primary source of unimodal visual inputs to the amygdala, and the amygdala sends back projects to TE. Previous studies in TE have suggested that it is involved in representing and remembering visual objects. A fundamental question in visual neurosciences to what extent affective value is inextricably linked to the basic representation of visual objects in the cortex. These experiments will address this question by determining the extent of affective signals present in TE. Ultimately, the experiments will address this question by determining the extent of affective signals present in TE. Ultimately, the approach taken in this project may provide the opportunity to improve understanding of psychiatric treatments by investigating how pharmacological interventions influence neural responses and emotional behavior in the alert monkey. The long-term career goal of the investigator is to establish a research program investigating the neural basis of emotions and emotional behavior. Stanford University and the laboratory of Dr. William Newsome, combined with the co-mentorship of Dr. Joseph LeDoux at New York University, provide a rich intellectual environment for the candidate to develop into an independent investigator. Participation in seminar, journal clubs, courses, scientific presentation sessions, and informal discussions with a large variety of faculty and trainees will form the basis of an intensive training program
Keywords: amygdala, association learning, emotion, neural information processing, visual stimulus, discrimination learning, limbic system, neurophysiology, psychological reinforcement, psychophysiology, Macaca mulatta, behavior test, behavioral /social science research tag
Project start date: 2000-05-10
Project end date: 2006-03-31
5K01MH001724-06 (2004): $176278
5K01MH001724-05 (2003): $176278
5K01MH001724-04 (2002): $176278
5K01MH001724-02 (2001): $169884
1K01MH001724-01A1 (2000): $166245
NEURAL MECHANISMS UNDERLYING REINFORCEMENT LEARNING
C Daniel Salzman
New York State Psychiatric Institute, New York, Ny 10032
Grant 5R01DA020656-04 from National Institute On Drug Abuse
Abstract: Dysfunction in neural circuits underlying emotional processes causes symptoms in a variety of neuropsychiatric disorders, including depression, anxiety disorders, schizophrenia, and drug abuse. Much work in animals and humans has implicated the amygdala in these emotional processes. In primates, however, amygdala neurophysiology has received limited attention, especially with regard to emotional learning. We propose using classical conditioning techniques so that monkeys learn the value of novel visual (Aim 1) or auditory (Aim 2) conditioned stimuli (CS). We assign CSs a value by arbitrarily pairing each CS with unconditioned stimuli (US) liquid reward (positive), air-puff (negative), or no reinforcement. Monkeys demonstrate their learning with two responses anticipatory licking for rewarded CSs, and anticipatory blinking, a defensive behavior, for negative CSs. We will record the activity of individual amygdala neurons in monkeys as they learn the value of the CSs. Theories of reinforcement learning posit that learning depends upon updating a neural representation of CS value, a process that is driven by error signals indicating the difference between expected and actual reinforcement. We hypothesize that amygdala neurons code the value of CSs, and that this representation is rapidly updated during learning. Furthermore, we hypothesize that amygdala neurons will respond differentially to unexpected compared to expected reinforcement, indicating that amygdala activity reflects error signals. Finally, we hypothesize that neurons whose activity reflects error signals are more likely to also encode CS value. In Aim 3, we seek to determine whether neural signals reflecting CS value during classical conditioning are best interpreted as coding for CS value or for expected reinforcement, which in more complex paradigms is not necessarily aligned with CS value. In classical conditioning studies, it is not possible to disambiguate these interpretations because CS value always predicts trial outcome. We will use an occasion setting paradigm in which expected outcome is manipulated by presenting a cue transiently before CS onset on a subset of probe trials, while maintaining individual CS value with regular conditioning trials. We will then determine if amygdala neurons represent CS value or expected outcome. These studies have direct relevance to public health, since these neural circuits dysfunction in many psychiatric disorders, including addiction, depression, and schizophrenia
Keywords: Air; Amygdala; Amygdaloid Body; Amygdaloid Nucleus; Amygdaloid structure; Animals; Anxiety Disorders; Associative Learning; Attention; Auditory; Aversive Stimulus; Behavior; Behavioral; Blinking; Cell Communication and Signaling; Cell Nucleus; Cell Signaling; Code; Coding System; Cognitive; Complex; Conditioning, Classical; Conditionings, Classical; Cues; Depression; Disease; Disorder; Drug abuse; Dysfunction; Emotional; Evaluation; Functional disorder; Goals; Human; Human, General; Image; Individual; Intracellular Communication and Signaling; Lateral; Learning; Link; Liquid substance; Mammals, Primates; Man (Taxonomy); Man, Modern; Mental Depression; Mental disorders; Mental health disorders; Methods and Techniques; Methods, Other; Modality; Modeling; Monkeys; Nerve Cells; Nerve Unit; Nervous; Neural Cell; Neurocyte; Neurons; Nucleus; Outcome; Pavlovian conditioning; Phase; Physiologic; Physiological; Physiopathology; Primates; Procedures; Process; Psychiatric Disease; Psychiatric Disorder; Psychological reinforcement; Public Health; Punishment; Reinforcement; Reinforcement (Psychology); Relative; Relative (related person); Rewards; Role; Schizophrenia; Schizophrenic Disorders; Science of neurophysiology; Sensory; Signal Transduction; Signal Transduction Systems; Signaling; Sound; Sound - physical agent; Stimulus; Symptoms; System; System, LOINC Axis 4; Techniques; Testing; Unspecified Mental Disorder; Update; Visual; Work; abuse of drugs; abuses drugs; addiction; amygdaloid nuclear complex; auditory stimulus; base; behavior measurement; behavioral measure; behavioral measurement; biological signal transduction; classical conditioning; conditioning; dementia praecox; disease/disorder; experience; experiment; experimental research; experimental study; eye blink; eyeblink; fluid; imaging; instrument; liquid; mental illness; motivated behavior; neural; neural circuit; neural circuitry; neural mechanism; neuromechanism; neuronal; neurophysiology; neuropsychiatric; neuropsychiatry; novel; pathophysiology; perceptual stimulus; physicochemical phenomena related to the senses; psychological disorder; public health medicine (field); reinforcer; relating to nervous system; research study; response; schizophrenic; sensory stimulus; social role; sound; theories; visual stimulus
Project start date: 2007-09-01
Project end date: 2012-06-30
Budget start date: 1-JUL-2010
Budget end date: 30-JUN-2011
5R01DA020656-04 (2010): $353371
5R01DA020656-03 (2009): $358038
Sponsored Links Excellgen http://Excellgen.com
5R01DA020656-02 (2008): $358413
1R01DA020656-01A2 (2007): $367257
C Daniel Salzman
Columbia University Health Sciences
Project start date: 2008-04-10
Project end date: 2013-01-31
Neurophysiology Underlying Neural Representations Of Value
C Daniel Salzman
Neurosciencecolumbia University Health Sciences
Grant 5R01MH082017-02 from National Institute Of Mental Health IRG: COG
Project start date: 2008-04-10
Project end date: 2013-01-31