John H Byrne
University Of Texas Hlth Sci Ctr Houston
Project start date: 1998-05-01
Project end date: 2013-01-31
Sponsored Links Excellgen http://Excellgen.com
Cellular Mechanisms Of Associative Learning
John H Byrne, Professor And Chair
Neurobiology And Anatomyuniversity Of Texas Hlth Sci Ctr Houston
box 20036
houston, Tx 77225
Grant 5R01MH058321-10 from National Institute Of Mental Health IRG: IFCN
Abstract: The overall goals of this project are to analyze and compare the mechanisms underlying the two major forms of associative learning, classical and operant conditioning. The proposed studies will focus on feeding behavior, which can be modified by both forms of learning, and which is amenable to cellular analyses. The Specific Aims of the proposed studies include 1. Investigate the cellular mechanisms of operant conditioning. For mechanistic analyses, a previously developed in vitro analogue of operant conditioning was reduced to a single cell (B51) in culture. This single-cell analogue induced changes in B51 that are similar to those induced by in vivo and in vitro conditioning. Aim 1 will 1) Characterize the modulation of membrane currents by contingent reinforcement; 2) Investigate the intracellular signals that mediate contingent reinforcement; and 3) Confirm that the cellular mechanisms elucidated in the single-cell analogue also occur in the ganglia and assess the contribution of changes in B51 to changes in the function of the feeding circuitry. 2. Characterize the role of B51 in classical conditioning. B51 is a locus of plasticity common to in vivo and in vitro operant and to in vivo classical conditioning. To examine the mechanisms underlying changes in B51 following classical conditioning, it is necessary to use the in vitro analogue. Thus, Aim 2 will 1) Complete the analysis of changes in B51 that are induced by in vivo training; 2) Confirm that the in vitro analogue of classical conditioning induces changes in B51 similar to those following in vivo conditioning; and 3) Investigate which second-messenger systems mediate the modulation of B51 and asses the contribution of changes in B51 to changes in the function of the feeding circuitry. 3. Identify and analyze additional sites of plasticity that contribute to classical and/or operant conditioning. Although several sites of plasticity have been identified, other sites are likely to contribute to classical and operant conditioning. Thus, Aim 3 will 1) Examine whether the in vitro analogues of classical and operant conditioning produce changes in the cellular and synaptic properties of sensory, command, pattern-initiating, and pattern-switching neurons in the feeding circuitry; and 2) Confirm that any changes produced by the in vitro analogues are also produced by in vivo training and examine the extent to which the changes are correlated with the behavioral modifications
Keywords: association learning, conditioning, eating, ethology, long term memory, neural information processing, neural plasticity, short term memory biophysics, central neural pathway /tract, electrostimulus, ganglion cell, neuroanatomy, neurotransmitter, nutrient intake activity, operant conditioning, psychological reinforcement, training Aplysia, behavioral /social science research tag, nutrition related tag, single cell analysis, voltage /patch clamp
Project start date: 1998-05-01
Project end date: 2009-02-28
5R01MH058321-10 (2007): $314659
5R01MH058321-09 (2006): $324057
5R01MH058321-08 (2005): $331855
5R01MH058321-07 (2004): $331855
5R01MH058321-04 (2001): $214201
5R01MH058321-03 (2000): $209346
CELLUAR MECHANISMS OF ASSOCIATIVE LEARNING
John H Byrne, Professor And Chair
Neurobiology And Anatomyuniversity Of Texas Hlth Sci Ctr Houston
box 20036
houston, Tx 77225
Grant 5R01MH058321-02 from National Institute Of Mental Health IRG: CFN
Abstract: Adapted from applicants ) The overall goal of this project is to investigate the cellular processes that underlie two forms of associate learning - classical conditioning and operant conditioning. Studies will focus on consummatory feeding behavior of Aplysia. This behavior can be modified by both classical and operant conditioning. Moreover, many key elements of the neural circuitry have been identified and this circuitry retains many of its functional characteristics in vitro. The project has four specific aims First, investigate cellular mechanisms underlying an in vitro analogue of operant conditioning. As a first step toward a cellular analysis of operant conditioning, we developed a preparation that retained the essential features of operant conditioning in vitro and was amenable to cellular analyses. The first aim is to identify and characterize the neuronal plasticities underlying this analogue of operant conditioning; identify cells and/or transmitters mediating the reinforcement; and investigate the cellular mechanisms encoding the temporal specificity of contingency-dependent neuronal plasticity. Second, develop an in vitro analogue of classical conditioning. To facilitate the cellular analysis of classical conditioning, we will develop an in vitro preparation that retains the essential features of classical conditioning and that is amenable to cellular analyses. The second aim is to characterize pathways mediating the reinforcement; to establish a stimulation protocol that mimics classical conditioning; and investigate cellular mechanisms underlying this in vitro analogue of associative learning. Third, identify neuronal correlates of classical and operant conditioning. Although the in vitro analogues may retain the essential features of associative learning, these reduced preparations are removed from the behaving animal. Thus, it is critical to explore loci and changes in the nervous systems of animals that have been behaviorally trained. The third aim is to determine whether the cellular loci that are modified by the in vitro analogues of associative learning (both classical and operant conditioning) are also modified by behavioral training; and to determine whether behavioral conditioning involves additional cellular loci. Fourth, compare cellular processes mediating short- (1 hr), intermediate- (~4 hr) and long-term memory (24 hr). The forth aim is to characterize and compare different temporal domains of memory that are induced by classical and operant condition; identify neuronal correlates for each phase of memory; and for each domain of memory, develop an in vitro analogue that will be amenable to cellular analyses. The proposed studies will provide the first major insights into the cellular mechanisms that underlie operant conditioning, as well as provide an opportunity for a mechanistic comparison of classical and operant conditioning
Keywords: association learning, conditioning, ethology, long term memory, neural information processing, neural plasticity, short term memory biophysics, brain /spinal pathway /tract, electrostimulus, ganglion cell, neuroanatomy, neurotransmitter, nutrient intake activity, operant conditioning, psychological reinforcement, training Aplysia, behavioral /social science research tag, nutrition related tag, patch clamp
Project start date: 1998-05-01
Project end date: 2003-02-28
5R01MH058321-02 (1999): $204634
Cellular Mechanisms Of Associative Learning
John H Byrne, Professor And Chair
Neurobiology And Anatomyuniversity Of Texas Hlth Sci Ctr Houston
Grant 5R01MH058321-12 from National Institute Of Mental Health IRG: LAM
Project start date: 1998-05-01
Project end date: 2013-01-31
Grants awarded to John H Byrne
Modeling Gene Regulation For Long-Term Plasticity
John H Byrne, Professor And Chair
University Of Texas Hlth Sci Ctr Houston Box 20036 Houston, Tx 77225
Grant 1R01NS050532-01 from National Institute Of Neurological Disorders And Stroke IRG: ZRG1
Abstract: This project wilt develop a framework based on mathematical modeling that a) describes the mechanism by which synaptic plasticity emerges from molecular processes regulating gene transcription, and b) tests mechanistic hypotheses, such asproposed roles of specific protein kinases. The project builds upon our previous model describing aspects of the gene and protein network responsible for long-term synaptic facilitation (LTF) and the formation of longterm memory (LTM) in the mollusk Aplysia. This model is based on transcriptional regulation by Ca2*/cAMP response element - binding protein (CREB, termed ApCREB1 in Aplysia) and related transcription factors. We will extend this model to incorporate additional elements of gene regulation recently demonstrated to be essential for LTF. In addition, we will develop an analogous model to simulate biochemical events underlying the induction of long-term synaptic potentiation (LTP) in vertebrates. Both LTF and LTP are thought to play essential roles in the formation of LTM, and the LTF induction and LTP induction exhibit mechanistic similarities, such as dependence on MAP kinase activation. Therefore, a modeling framework that can simulate aspects of both LTF and LTP induction is likely to significantly increase the understanding of learning mechanisms. The LTF model variant will incorporate additional transcriptional regulators essential for LTF, such as ApCREB2, and ApC/EBP. Bifurcation analysis and pre-programmed integrations will identify key control parameters which are plausible sites of physiological regulation and which, when varied, have important effects on the dynamics of the model. We will then use the model to simulate the results of experimental protocols in which alterations are made in the activity of the transcriptional regulators listed above. A minimal set of variations in key control parameters will be identified that allows simulation of data from these protocols. This approach is likely to help identify the key mechanisms that determine the amount of LTF induced by different training protocols. The LTP model variant will be used to simulate three common stimulus protocols that induce hippocampal late LTP. These protocols are high-frequency (tetanic) stimulation, theta-burst stimulation, and stimulation by forskolin. Parameters will be optimized to fit experimental time courses of nuclear [Ca 2+] and of kinase and transcription factor activities. The model will then be used to test the hypothesis that CREB kinases other than protein kinase A, such as ribosomal $6 kinase 2, are primarily responsible for CREB phosphorylation and LTP induction.
Keywords: gene expression, genetic regulation, learning, mathematical model, model design /development, neural plasticity, neurogenetics, biological signal transduction, cAMP response element binding protein, calcium flux, computer simulation, enzyme activity, enzyme inhibitor, hippocampus, long term memory, long term potentiation, neural facilitation, neurochemistry, neuropharmacology, phosphorylation, protein kinase, serotonin, transcription factor, Aplysia, alternatives to animals in research
Project start date: 2004-09-15
Project end date: 2006-07-31
1R01NS050532-01 (2004): $273559
MODELING GENE REGULATION ESSENTIAL FOR LONG-TERM SYNAPTIC PLASTICITY
John H Byrne, Professor/chairman
University Of Texas Hlth Sci Ctr Houston, Box 20036, Houston, Tx 77225
Abstract: This project will develop a framework based on mathematical modeling that a) describes the mechanism by which synaptic plasticity emerges from molecular processes regulating gene transcription, and b) tests mechanistic hypotheses, such as proposed roles of specific protein kinases. The project builds upon our previous model describing aspects of the gene and protein network responsible for long-term synaptic facilitation (LTF) and the formation of long-term memory (LTM) in the mollusk Aplysia. This model is based on transcriptional regulation by Ca2+/cAMP response element - binding protein (CREB, termed ApCREBI in Aplysia) and related transcription factors. We will extend this model to incorporate additional elements of gene regulation recently demonstrated to be essential for LTF. In addition, we will develop an analogous model to simulate biochemical events underlying the induction of late long-term synaptic potentiation (L-LTP) in vertebrates. Both LTF and L-LTP are thought to play essential roles in the formation of LTM, and LTF induction and L-LTP induction exhibit mechanistic similarities, such as dependence on MAP kinase activation. Therefore, a modeling framework that can simulate aspects of both LTF and L-LTP induction is likely to significantly increase the understanding of learning mechanisms. The LTF model variant will incorporate additional transcriptional regulators essential for LTF, such as ApCREB2, and ApC/EBP. Bifurcation analysis and pre-programmed integrations will identify key control parameters which are plausible sites of physiological regulation and which, when varied, have important effects on the dynamics of the model. We will then use the model to simulate the results of experimental protocols in which alterations are made in the activity of the transcriptional regulators listed above. A minimal set of variations in key control parameters will be identified that allows simulation of data from these protocols. This approach is likely to help identify the key mechanisms that determine the amount of LTF induced by different training protocols. The L-LTP model variant will be used to simulate three common stimulus protocols that induce hippocampal L-LTP. These protocols are high-frequency (tetanic) stimulation, theta-burst stimulation, and stimulation by forskolin. Parameters will be optimized to fit experimental time courses of nuclear [Ca2+] and of kinase and transcription factor activities. The model will then be used to test the hypothesis that CREB kinases other than protein kinase A, such as ribosomal S6 kinase 2, are primarily responsible for CREB phosphorylation and LTP induction. Preliminary model development and simulations predict that L-LTP induction by a low-frequency burst stimulus protocol does not depend on nuclear CaM kinase activation and consequent CREB phosphorylation
Keywords: 1H-Naphtho(2, 1-b)pyran-1-one, 5-(acetyloxy)-3-ethenyldodecahydro-6, 10, 10b-trihydroxy-3, 4a, 7, 7, 10a-pentamethyl-; ATP-protein phosphotransferase; Adenosine Cyclic Monophosphate-Dependent Protein Kinases; Ammon Horn; Aplysia; Biochemical; CRE Binding Protein; CREB; CREB Protein; CREB1; CREB1 gene; Chemosensitization; Chemosensitization/Potentiation; Coleonol; Cornu Ammonis; Cyclic AMP Response Element-Binding Protein; Cyclic AMP Responsive Element Binding Protein; Cyclic AMP-Dependent Protein Kinases; Cyclic AMP-Responsive DNA-Binding Protein; Data; Dependence; EC 2.7; EC 2.7.2-; Elements; Event; Exhibits; Extracellular Signal-Regulated Kinases; Forskolin; Frequencies (time pattern); Frequency; Gene Action Regulation; Gene Expression Regulation; Gene Proteins; Gene Regulation; Gene Regulation Process; Gene Transcription; Genetic Transcription; Hippocampus; Hippocampus (Brain); Kinases; Learning; MAP kinase; MAP-kinase-activated protein kinase 1b; MAPK; MAPKAP kinase-1b; Math Models; Mitogen-Activated Protein Kinases; Modeling; Molecular; Nuclear; PKA; Phosphorylation; Phosphotransferases; Physiologic; Physiological; Play; Potentiation; Process; Programs (PT); Programs [Publication Type]; Protein Gene Products; Protein Kinase; Protein Kinase A; Protein Phosphorylation; Protocol; Protocols documentation; RNA Expression; RSK kinase II; RSK2 Kinase; Regulation; Role; Simulate; Site; Stimulus; Synapses; Synaptic; Synaptic plasticity; Testing; Time; Training; Transcription; Transcription Regulation; Transcription, Genetic; Transcriptional Control; Transcriptional Regulation; Transphosphorylases; Variant; Variation; Vertebrate Animals; Vertebrates; base; cAMP Response Element-Binding Protein; cAMP Responsive Element Binding Protein; cAMP-Dependent Protein Kinases; glycogen synthase a kinase; hippocampal; hydroxyalkyl protein kinase; long term memory; mathematical model; mathematical modeling; model development; neural model; phosphorylase b kinase kinase; programs; ribosomal S6 kinase 2; ribosomal protein S6 kinase 2; ribosomal protein S6 kinase II; ribosomal protein S6 kinase, 90kD, polypeptide 3; simulation; social role; transcription factor; vertebrata
Budget start date: 1-JUL-2009
Budget end date: 30-JUN-2010
5P01NS038310-10_0001 (2009): $289428
John H Byrne, Professor And Chair
Neurobiology And Anatomyuniversity Of Texas Hlth Sci Ctr Houston
box 20036
houston, Tx 77225
Grant 5R01NS019895-19 from National Institute Of Neurological Disorders And Stroke IRG: NEUB
Abstract: The overall objective of the proposed research is to provide insights into one of the most fundamental problems in the neurosciences - the physiological basis of learning and memory. There are three broad aspects of this topic that will be investigated. The first aim is to continue to elucidate the mechanisms of synaptic plasticity that underlies short-term sensitization. Of particular interest will be the interaction of multiple second messenger pathways. Specific objectives of this first aim include 1) identify the second messenger(s) that mediates the 5-HT-induced modulation of the voltage-dependent delayed K+ channel; 2) Determine the contribution of CaMKII to FMRFamide-induced spike narrowing; 3) identify the second messenger mediating the inhibitory effect of FMRFamide on mobilization and characterize its role in sensitization; and 4) Characterize the currents modulated by a sensitizing stimulus. A second major goal is to investigate the unique mechanisms underlying long-term sensitization from two perspectives its induction and its expression. Specific objectives of this second and third aim include 1) Determine the role of cAMP in the induction of long-term synaptic plasticity of sensorimotor connections; 2) Determine the time window of the requirement for gene transcription and protein translation; 3) Examine the time course of long-term plasticity at points longer than 24 hr after training; 4) Determine the role of apTBL-1 in long-term synaptic plasticity; 5) Determine the role of TGF-beta and other growth factors in long-term facilitation. The final aim of the proposal examines distributed representations of learning and memory and seeks to determine whether mechanisms for induction, maintenance and expression are shared among different sites. Although a great deal is known about plasticity at the sensorimotor synapse, modification of other sites in the circuit will be investigated in order to understand the full expression of the behavioral modification. Specific objectives of this aim include 1) Determine the contribution of interneurons to short-term sensitization; 2) Determine the contribution of interneurons to long-term sensitization; 3) Examine the effects of modulatory transmitters; and 4) Examine the ionic mechanisms and possible second messengers involved in the short-and long-term changes in the properties of the interneurons and motor neurons
Keywords: electrophysiology, learning, memory, molecular psychobiology, neural plasticity, neuroanatomy calmodulin dependent protein kinase, cyclic AMP, genetic transcription, genetic translation, growth factor, interneuron, motor neuron, neurotransmitter, second messenger Aplysia, behavioral /social science research tag
Project start date: 1983-04-01
Project end date: 2002-11-30
5R01NS019895-19 (2001): $254727
5R01NS019895-18 (2000): $247304
5R01NS019895-17 (1999): $254214
3R01NS019895-17S1 (1999): $175000
Sponsored Links Excellgen http://Excellgen.com
ANALYSIS OF THE NEURAL CONTROL OF BEHAVIOR
John H Byrne, Professor And Chair
University Of Texas Hlth Sci Ctr Houston Box 20036 Houston, Tx 77225
Grant 5R01NS019895-12 from National Institute Of Neurological Disorders And Stroke IRG: NEUB
Abstract: The overall objective of the proposed research is to provide insights into one of the most fundamental problems in the neurosciences - the physiological basis of learning and memory. The project has three specific aims. The first aim analyzes mechanisms underlying alterations in both the biochemical and biophysical properties of individual neurons and the strength of synaptic connections between neurons that are associated with a simple form of learning known as sensitization. It examines the complex interactions between the activation of second messenger systems and the modulation of membrane currents and the facilitation of transmitter release. Specific objectives of this first aim include 1) To determine whether the delayed potassium current is modulated by sensitizing stimuli and how the time course of this modulation compares to that of sensitization and synaptic facilitation; 2) To determine the second messenger(s) and protein kinase(s) that modulate the current; 3) To examine the time-dependence and interactions among second messengers in early and intermediate-term synaptic facilitation; and 4) To examine whether the sodium current is regulated by modulatory transmitters. The second aim addresses a fundamental issue in the cellular analysis of memory the relationships between the cellular loci and the mechanisms of short- and long-lasting memories. Specific objectives of this second aim include 1) To establish the electrophysiological correlates of long-term information storage following sensitization training and to compare these changes to those induced by transiently elevated levels of the second messenger, cAMP; 2) To determine the contribution of gene transcription and translation to the electrophysiological changes induced by sensitization training; and 3) To determine whether there are multiple stages of long-term memory. The final aim of the proposal examines distributed representations of learning and memory and seeks to determine whether mechanisms for induction, maintenance and expression are shared among different sites. Specific objectives of this third aim include 1) To examine and analyze short-term plastic properties of interneurons and modulatory neurons; 2) To determine whether interneurons are involved in the storage of memory for long-term sensitization; and 3) To examine the ionic mechanisms and possible second messengers involved in modulation of the properties of interneurons. Learning and memory are unquestionably important components of biological intelligence and manifest themselves in aspects of cognitive function, language and motor control. Knowledge of the fundamental mechanisms underlying learning and memory are necessary to understand these complex functions of the brain. The application of this knowledge may lead to an understanding and treatment of learning disabilities.
Keywords: learning, molecular psychobiology, neural information processing, neural plasticity, alternatives to animals in research, behavioral habituation /sensitization, conditioning, genetic transcription, genetic translation, interneuron, memory, neural facilitation, potassium channel, protein kinase, second messenger, sodium channel, Aplysia, electrophysiology
Project start date: 1983-04-01
Project end date: 1997-03-31
5R01NS019895-12 (1994): $207135
John H Byrne, Professor And Chair
University Of Texas Hlth Sci Ctr Houston Box 20036 Houston, Tx 77225
Grant 2R01NS019895-11 from National Institute Of Neurological Disorders And Stroke IRG: NEUB
Abstract: The overall objective of the proposed research is to provide insights into one of the most fundamental problems in the neurosciences - the physiological basis of learning and memory. The project has three specific aims. The first aim analyzes mechanisms underlying alterations in both the biochemical and biophysical properties of individual neurons and the strength of synaptic connections between neurons that are associated with a simple form of learning known as sensitization. It examines the complex interactions between the activation of second messenger systems and the modulation of membrane currents and the facilitation of transmitter release. Specific objectives of this first aim include 1) To determine whether the delayed potassium current is modulated by sensitizing stimuli and how the time course of this modulation compares to that of sensitization and synaptic facilitation; 2) To determine the second messenger(s) and protein kinase(s) that modulate the current; 3) To examine the time-dependence and interactions among second messengers in early and intermediate-term synaptic facilitation; and 4) To examine whether the sodium current is regulated by modulatory transmitters. The second aim addresses a fundamental issue in the cellular analysis of memory the relationships between the cellular loci and the mechanisms of short- and long-lasting memories. Specific objectives of this second aim include 1) To establish the electrophysiological correlates of long-term information storage following sensitization training and to compare these changes to those induced by transiently elevated levels of the second messenger, cAMP; 2) To determine the contribution of gene transcription and translation to the electrophysiological changes induced by sensitization training; and 3) To determine whether there are multiple stages of long-term memory. The final aim of the proposal examines distributed representations of learning and memory and seeks to determine whether mechanisms for induction, maintenance and expression are shared among different sites. Specific objectives of this third aim include 1) To examine and analyze short-term plastic properties of interneurons and modulatory neurons; 2) To determine whether interneurons are involved in the storage of memory for long-term sensitization; and 3) To examine the ionic mechanisms and possible second messengers involved in modulation of the properties of interneurons. Learning and memory are unquestionably important components of biological intelligence and manifest themselves in aspects of cognitive function, language and motor control. Knowledge of the fundamental mechanisms underlying learning and memory are necessary to understand these complex functions of the brain. The application of this knowledge may lead to an understanding and treatment of learning disabilities.
Keywords: learning, molecular psychobiology, neural information processing, neural plasticity, alternatives to animals in research, behavioral habituation /sensitization, conditioning, genetic transcription, genetic translation, interneuron, memory, neural facilitation, potassium channel, protein kinase, second messenger, sodium channel, Aplysia, electrophysiology
Project start date: 1983-04-01
Project end date: 1997-03-31
2R01NS019895-11 (1993): $199460
2R01NS019895-15 (1997): $262454
Cellular Mechanisms Of Associative Learning
John H Byrne, Professor And Chair
University Of Texas Hlth Sci Ctr Houston Box 20036 Houston, Tx 77225
Grant 2R01MH058321-06 from National Institute Of Mental Health IRG: IFCN
Abstract: The overall goals of this project are to analyze and compare the mechanisms underlying the two major forms of associative learning, classical and operant conditioning. The proposed studies will focus on feeding behavior, which can be modified by both forms of learning, and which is amenable to cellular analyses. The Specific Aims of the proposed studies include 1. Investigate the cellular mechanisms of operant conditioning. For mechanistic analyses, a previously developed in vitro analogue of operant conditioning was reduced to a single cell (B51) in culture. This single-cell analogue induced changes in B51 that are similar to those induced by in vivo and in vitro conditioning. Aim 1 will 1) Characterize the modulation of membrane currents by contingent reinforcement; 2) Investigate the intracellular signals that mediate contingent reinforcement; and 3) Confirm that the cellular mechanisms elucidated in the single-cell analogue also occur in the ganglia and assess the contribution of changes in B51 to changes in the function of the feeding circuitry. 2. Characterize the role of B51 in classical conditioning. B51 is a locus of plasticity common to in vivo and in vitro operant and to in vivo classical conditioning. To examine the mechanisms underlying changes in B51 following classical conditioning, it is necessary to use the in vitro analogue. Thus, Aim 2 will 1) Complete the analysis of changes in B51 that are induced by in vivo training; 2) Confirm that the in vitro analogue of classical conditioning induces changes in B51 similar to those following in vivo conditioning; and 3) Investigate which second-messenger systems mediate the modulation of B51 and asses the contribution of changes in B51 to changes in the function of the feeding circuitry. 3. Identify and analyze additional sites of plasticity that contribute to classical and/or operant conditioning. Although several sites of plasticity have been identified, other sites are likely to contribute to classical and operant conditioning. Thus, Aim 3 will 1) Examine whether the in vitro analogues of classical and operant conditioning produce changes in the cellular and synaptic properties of sensory, command, pattern-initiating, and pattern-switching neurons in the feeding circuitry; and 2) Confirm that any changes produced by the in vitro analogues are also produced by in vivo training and examine the extent to which the changes are correlated with the behavioral modifications.
Keywords: association learning, conditioning, eating, ethology, long term memory, neural information processing, neural plasticity, short term memory, biophysics, brain /spinal pathway /tract, electrostimulus, ganglion cell, neuroanatomy, neurotransmitter, nutrient intake activity, operant conditioning, psychological reinforcement, training, Aplysia, behavioral /social science research tag, nutrition related tag, single cell analysis, voltage /patch clamp
Project start date: 1998-05-01
Project end date: 2008-02-28
2R01MH058321-06 (2003): $332406
ANALYSIS OF THE NEURAL CONTROL OF BEHAVIOR
John H Byrne, Professor And Chair
University Of Pittsburgh At Pittsburgh 350 Thackeray Hall Pittsburgh, Pa 15260
Grant 5R01NS019895-03 from National Institute Of Neurological Disorders And Stroke IRG: NEUB
Abstract: The overall goal of this proposal is to test systematically complementary hypotheses about the physiological function of decreased conductance depolarizing potentials in the nervous system. One hypothesis is that decreased conductance depolarizing potentials (DCDPs) are used as a general integrative and modulatory mechanism to enhance and integrate related behavioral actions by coordinately increasing the excitability and synaptic efficacy of sensory, motor, and interneuronal elements in neural circuits underlying synergistic responses. A related hypothesis is that DCDPs, through their effects on major cellular regulators such as cyclic nucleotides and Ca++, play an important role in the generation of long-lasting neuronal modifications underlying associative and nonassociative learning. These hypotheses will be tested by examining the cellular changes accompanying the elicitation and modulation of a coordinated ensemble of defensive responses in the mollusc Aplysia by stimulation of its tail. Each response - tail withdrawal, gill withdrawal, inking, opaline release, and respiratory pumping - involves circuits in which major sensory, motor, and interneurons have been identified. Using electrophysiological and pharmacological techniques we will determine the loci in the circuits where DCDPs operate, the conditions under which they are triggered, and the contribution they make to the functional properties of the cells. In selected cells (the tail sensory neurons and ink motoneurons) presenting perticular advantages for detailed analysis, we will use voltage clamp, computer simulation, and biochemical techniques to examine the biophysical and biochemical mechanisms by which the DCDPs are produced and, in addition, systematically analyze the mechanisms by which DCDPa can be altered by paired spike activity in the cell and thus contribute to associative modifications that may play a role in learning. These analyses may lead not only to a greater understanding of the cellular mechanisms underlying neural integration, arousal and learning but may also lead to a refinement of techniques which may then be more readily applied to the analysis of behavioral control, modifiability and abnormalities in more complex organisms, including man.
Keywords: INFORMATION PROCESSING AND CONTROL (NEURAL), NEUROLOGY B STUDY SECTION, NEUROPHYSIOLOGY, REFLEX, PSYCHOBIOLOGY, PSYCHOPHYSIOLOGY, PSYCHOLOGY, BRAIN CONTROL, PSYCHOLOGY, LEARNING, BIOCHEMISTRY, ELECTROPOTENTIALS, NERVOUS SYSTEM, NERVE ENDINGS, SYNAPSES, NEUROPHYSIOLOGY, NEURAL TRANSMISSION, NEUROPHYSIOLOGY, NEUROPLASTICITY, PSYCHOLOGY, NEUROPSYCHOLOGY (GENERAL), STIMULUS-RESPONSE (GENERAL), neuroanatomy, BIOMEDICAL SYSTEMS AUTOMATED, COMPUTER PROCESSING OF LABORATORY DATA (GENERAL), BIOPHYSICS (GENERAL), MOLLUSKS, GASTROPODS, WATER ENVIRONMENT, AQUATIC ORGANISMS, MARINE, computer simulation, electrophysiology, neurochemistry, neuropharmacology
Project start date: 1983-04-01
Project end date: 1986-03-31
2R01NS019895-20A1 (2003): $350374
Neural Models Of Plasticity: Molecules To Networks
John H Byrne, Professor And Chair
Neurobiology And Anatomyuniversity Of Texas Hlth Sci Ctr Houston
box 20036
houston, Tx 77225
Grant 5P01NS038310-09 from National Institute Of Neurological Disorders And Stroke IRG: NSD
Abstract: The main function of the nervous system is to process information in ways that lead to adaptive behavior. Two different approaches, one theoretical and the other empirical, are being used to explore the role of neuronal plasticity in development, learning, memory, information processing, and other complex brain functions. The theoretical approach simulates and synthesizing brain function with mathematical models based on known and hypothesized principles of neural function. The empirical approach delineates the complex biochemical and biophysical properties of neurons, the rules that determine their connectivity, and the mechanisms through which their properties and connections are modified during development and learning. Although these two approaches have traditionally been used independently, there is a growing realization among neurobiologists, psychologists, and adaptive systems theorists that progress in understanding the brain is dependent on a combination of both approaches. In addition, in many cases, the knowledge of systems has matured to the point where there is not only a sufficient body of information to warrant a computational approach, but further progress in the understanding of the system requires it. The overall goal of the Program Project is to use computational approaches to examine neuronal plasticity at multiple levels of organization, ranging from molecular dynamics within subcellular neuronal compartments, to genetic networks within neurons, to neural network mechanisms. The individual Projects are linked by the common goal of investigating plasticity in neurons in the hippocampus and related structures and determining its contributions to higher levels of processing. The individual Projects will examine 1) the dynamical properties of gene networks underlying plasticity; 2) the quantitative behavior of the postsynaptic Ca2+/calmodulin signaling pathway that plays an essential role in neuronal plasticity; 3) dynamics of synaptic plasticity at the molecular level and its importance as a substrate for plasticity in the hippocampus; and 4) the neural network mechanisms by which the hippocampus constructs high-order cognitive representations from multimodal inputs. In addition, the individual Projects will be supported by a Computational Core Facility that will serve as a resource for developing computational models and for the exchange of information among the projects
Keywords: computational neuroscience, model design /development, neural plasticity
Project start date: 2000-06-01
Project end date: 2010-06-30
5P01NS038310-09 (2008): $988723
5P01NS038310-08 (2007): $1033684
5P01NS038310-07 (2006): $1089124
Sponsored Links Excellgen http://Excellgen.com
2P01NS038310-06A2 (2005): $1147161
NEURAL MODELS OF PLASTICITY: MOLECULAR TO NETWORKS
John H Byrne, Professor And Chair
Neurobiology And Anatomyuniversity Of Texas Hlth Sci Ctr Houston
box 20036
houston, Tx 77225
Grant 5P01NS038310-03 from National Institute Of Neurological Disorders And Stroke IRG: ZNS1
Abstract: The main function of the nervous system is to process information in ways that lead to adaptive behavior, and to accomplish this, the excitability of neurons and the strength of their synaptic connections need to be modulated continually. After a neuron or neural system has been analyzed extensively, it becomes possible to ask what information it carries and how it contributes to this plasticity. At this point, there is generally so much data that only computational approaches can explain how individual components of a system interact, however. This Program Project will apply constructionistic computational techniques to several such well- characterized neural systems to achieve a more complete understanding of neuronal information processing and plasticity. The Project will examine multiple levels of organization, ranging from genetic networks within neurons to neural circuit. The individual projects will examine 1) the dynamic properties and interactions of gene networks and excitable membranes; 2) the contribution of plasticity in individual neurons to associative learning; 3) the computational role of cellular and synaptic plasticity in an oscillatory neural circuit; and 4) the role of dopamine in light and dark adaptation in the primate retina. The individual projects are linked by a common goal of investigating plasticity in neurons and determining its contributions to higher levels of processing. For example, simulation of simple forms of cellular and synaptic plasticity may provide insights into the roles of these distinct mechanisms in the information processing capabilities of larger-scale neural networks such as those controlling feeding behavior. The group will be supported by a Computational Core that serves as a resource for developing models and for the exchange of information among the project groups. Another important goal of the project is to train graduate students and postdoctoral fellows in Computational Neuroscience. Finally, the Projects will further develop general-purpose simulation programs for neuronal and biochemical modeling, which will be used by the Program Project group. These programs will also be widely distributed to other groups who wish to apply computational approaches to analyze the properties of nerve cells and neuronal networks
Keywords: computational neuroscience, neural plasticity
Project start date: 1999-08-25
Project end date: 2004-05-31
5P01NS038310-03 (2001): $1001226
5P01NS038310-02 (2000): $992170
1P01NS038310-01A1 (1999): $969287
NETWORK, CELLULAR AND MOLECULAR DETERMINANTS OF LEARNING
John H Byrne, Professor And Chair
University Of Texas Hlth Sci Ctr Houston Box 20036 Houston, Tx 77225
Grant 5K05MH000649-10 from National Institute Of Mental Health IRG: CFN
Abstract: A fundamental problem in neuroscience is to understand events occurring within Individual neurons and within neural networks that contribute to forms of plasticity underlying learning and memory. This proposal outlines both empirical and modeling studies that will examine the molecular, biochemical and biophysical properties of Identified neurons and the connectivity of neural circuits that have demonstrated capacities for nonassociative and associative plasticity. Specifically, the neural circuit that mediates the tail withdrawal reflex will be analyzed. Many of the sensory neurons, Interneurons, motor neurons and modulatory interneurons that control this behavior have been Identified and are accessible to study. Thus, molecular, biochemical and cellular neurophysiological techniques will be applied to analyze the particular processes that might explain associative and nonassociative learning. Formalisms of the cellular and network processes that underlie these forms of plasticity will be developed and incorporated into quantitative, real-time models of neuron-like elements and neural networks. The ability of these models to fit the experimental data and to predict simple and complex features of learning will be examined. The proposed research will provide for a fairly complete analysis of the mechanisms underlying the Induction, expression and maintenance of simple forms of nonassociative and associative learning as well as help address fundamental questions regarding the mechanistic relationship between short- and long-term memories.
Keywords: association learning, learning, long term memory, molecular psychobiology, neural information processing, neural plasticity, short term memory, afferent nerve, computational neuroscience, gene expression, genetic transcription, genetic translation, interneuron, motor neuron, neural transmission, neurofilament protein, neuron, neurophysiology, phosphorylation, posttranslational modification, protein biosynthesis, second messenger, synapse, Aplysia, SDS polyacrylamide gel electrophoresis, alternatives to animals in research, behavioral /social science research tag, electrophysiology, radiotracer
Project start date: 1986-09-30
Project end date: 1998-06-30
5K05MH000649-10 (1997): $102951
5K05MH000649-08 (1995): $102951
5K05MH000649-07 (1994): $102951
2K05MH000649-06A2 (1993): $102951
ANALYSIS OF THE NEURAL CONTROL OF BEHAVIOR
John H Byrne, Professor And Chair
University Of Texas Hlth Sci Ctr Houston Box 20036 Houston, Tx 77225
Grant 5R01NS019895-10 from National Institute Of Neurological Disorders And Stroke IRG: NEUB
Abstract: A classical conditioning protocol applied directly to individual tail sensory neurons in Aplysia results in an associative modification of the monosynaptic connections to tail motor neurons. Sensory neurons receiving a conditioned stimulus (CS, intracellular activation of the sensory neuron) immediately before the unconditioned stimulus (US, tail shock) show significantly more synaptic facilitation than sensory neurons exposed to the US alone or to unpaired CS and US applications. An analog of the classical conditioning paradigm produces a selective amplification of the cAMP content of isolated sensory neuron clusters. These results indicate that a pairing-specific enhancement of cAMP levels may be a biochemical mechanism for associative learning. Experiments proposed here are designed to extend these analyses. Specifically, we will examine 1) whether Ca2+ serves as the signal for the induction of the associative change, 2) whether cAMP levels in the sensory neurons are increased during simple forms of learning such as sensitization and classical conditioning, 3) the contribution of spike broadening in the sensory neurons to synaptic facilitation and behavioral modifications, 4) the properties of the neural circuit elements mediating the tail withdrawal reflex and effects of the US, and 5) the coordination of synergistic defensive responses triggered by tail stimulation. The tail withdrawal reflex offers a unique opportunity to investigate the cellular and molecular basis of learning. Few systems offer all the advantages found in this preparation; a simple stereotyped behavior for which the neural circuitry is relatively well defined, a large homogeneous population of identifiable cells that are accessible for biochemical and biophysical assay, and a testable hypothesis. Continued analysis of this system promises to yield much additional information concerning the cellular mechanisms underlying associative and nonassociative learning.
Keywords: association learning, biophysics, mind control, molecular psychobiology, neural information processing, psychobiology, reflex, afferent nerve, conditioning, cyclic AMP, electrical potential, motor neuron, neural plasticity, neural transmission, neuroanatomy, neurochemistry, neuropsychology, stimulus /response, synapse, Aplysia, computer processing of laboratory data, electrophysiology, neuropharmacology
Project start date: 1983-04-01
Project end date: 1993-03-31
5R01NS019895-10 (1992): $158946
Sponsored Links Excellgen http://Excellgen.com
John H Byrne
University Of Texas Hlth Sci Ctr Houston
Project start date: 1983-04-01
Project end date: 2013-01-31
Analysis Of The Neural Control Of Behavior
John H Byrne, Professor And Chair
Neurobiology And Anatomyuniversity Of Texas Hlth Sci Ctr Houston
Grant 5R01NS019895-26 from National Institute Of Neurological Disorders And Stroke IRG: LAM
Project start date: 1983-04-01
Project end date: 2013-01-31
John H Byrne, Professor And Chair
University Of Texas Hlth Sci Ctr Houston Box 20036 Houston, Tx 77225
Grant 1S10RR022531-01A1 from National Center For Research Resources IRG: ZRG1
Keywords: microscopy, anatomy, art, cell, cold temperature, electromagnetic radiation, housing, humidity, laser, morphology, neurobiology, neuron, performance, university
Project start date: 2007-04-01
Project end date: 2008-03-31
1S10RR022531-01A1 (2007): $268895
Analysis Of The Neural Control Of Behavior
John H Byrne, Professor And Chair
University Of Texas Hlth Sci Ctr Houston Box 20036 Houston, Tx 77225
Grant 5R01NS019895-24 from National Institute Of Neurological Disorders And Stroke IRG: IFCN
Keywords: behavior, neuroregulation, role, synapsin, university, Aplysia, Leguminoseae, attention, base, behavioral habituation /sensitization, face, health, insight, learning, long term memory, memory, model, motor neuron, neuron, neuroscience, phosphorylation, play, protein, protein kinase, receptor, synapse, synaptic vesicle, thinking, training
Project start date: 1983-04-01
Project end date: 2008-01-31
5R01NS019895-24 (2007): $334412
5R01NS019895-23 (2006): $344400
Sponsored Links Excellgen http://Excellgen.com
5R01NS019895-22 (2005): $352688
5R01NS019895-21 (2004): $347109
NETWORK, CELLULAR AND MOLECULAR DETERMINANTS OF LEARNING
John H Byrne, Professor And Chair
Neurobiology And Anatomyuniversity Of Texas Hlth Sci Ctr Houston
box 20036
houston, Tx 77225
Grant 5K05MH000649-09 from National Institute Of Mental Health IRG: CFN
Project start date: 1986-09-30
Project end date: 1998-06-30
5K05MH000649-09 (1996): $86747
ANALYSIS OF THE NEURAL CONTROL OF BEHAVIOR
John H Byrne, Professor And Chair
Neurobiology And Anatomyuniversity Of Texas Hlth Sci Ctr Houston
box 20036
houston, Tx 77225
Grant 5R01NS019895-14 from National Institute Of Neurological Disorders And Stroke IRG: NEUB
Project start date: 1983-04-01
Project end date: 1997-03-31
5R01NS019895-14 (1996): $225152