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6401. Toward an integrated approach to perception and action: conference report and future directions
- Title:
- Toward an integrated approach to perception and action: conference report and future directions
- Original Bibliographic Citation:
- Gordon G, Kaplan DM, Lankow B, Little DY, Sherwin J, Suter BA, Thaler L. (2011) Toward an integrated approach to perception and action: conference report and future directions. Front Syst Neurosci. 5:20.
- Abstract:
- This article was motivated by the conference entitled "Perception & Action - An Interdisciplinary Approach to Cognitive Systems Theory," which took place September 14-16, 2010 at the Santa Fe Institute, NM, USA. The goal of the conference was to bring together an interdisciplinary group of neuroscientists, roboticists, and theorists to discuss the extent and implications of action-perception integration in the brain. The motivation for the conference was the realization that it is a widespread approach in biological, theoretical, and computational neuroscience to investigate sensory and motor function of the brain in isolation from one another, while at the same time, it is generally appreciated that sensory and motor processing cannot be fully separated. Our article summarizes the key findings of the conference, provides a hypothetical model that integrates the major themes and concepts presented at the conference, and concludes with a perspective on future challenges in the field.
- Keyword:
- Neuroscience, Neocortex
- Subject: MESH:
- Perception--physiology, Sensorimotor Cortex--physiology, Sensation--physiology, Models, Neurological, Movement--physiology, Robotics, Brain--physiology
- Creator:
- Suter, Benjamin
- Publisher:
- Frontiers Media, DigitalHub. Galter Health Sciences Library
- Language:
- English
- Date Created:
- 2011
- Rights:
- http://creativecommons.org/licenses/by/3.0/us/
- Resource Type:
- Journal Article
- Original Identifier:
- (PMID)21541257
- Title:
- Reciprocal Interareal Connections to Corticospinal Neurons in Mouse M1 and S2
- Original Bibliographic Citation:
- Suter, Benjamin A., Shepherd, Gordon M.G. (2015) Reciprocal Interareal Connections to Corticospinal Neurons in Mouse M1 and S2. J Neurosci 35:2959-2974.
- Abstract:
- Primary motor (M1) and secondary somatosensory (S2) cortices, although anatomically and functionally distinct, share an intriguing cellular component: corticospinal neurons (CSP) in layer 5B. Here, we investigated the long-range circuits of CSPs in mouse forelimb-M1 and S2. We found that interareal projections (S2 M1 and M1 S2) monosynaptically excited pyramidal neurons across multiple layers, including CSPs. Area-specific differences were observed in the relative strengths of inputs to subsets of CSPs and other cell types, but the general patterns were similar. Furthermore, subcellular mapping of the dendritic distributions of these corticocortical excitatory synapses onto CSPs in both areas also showed similar patterns. Because layer 5B is particularly thick in M1, but not S2, we studied M1-CSPs at different cortical depths, quantifying their dendritic morphology and mapping inputs from additional cortical (M2, contralateral M1, and local layer 2/3) and thalamic (VL nucleus) sources. These results indicated that CSPs exhibit area-specific modifications on an otherwise conserved synaptic organization, and that different afferents innervate M1-CSP dendritic domains in a source-specific manner. In the cervical spinal cord, CSP axons from S2 and M1 partly converged on middle layers, but S2-CSP axons extended further dorsally, and M1-CSP axons ventrally. Thus, our findings identify many shared features in the circuits of M1 and S2 and show that these areas communicate via mutual projections that give each area monosynaptic access to the other area's CSPs. These interareally yoked CSP circuits may enable M1 and S2 to operate in a coordinated yet differentiated manner in the service of sensorimotor integration.
- Keyword:
- Neuroscience, Neocortex
- Subject: MESH:
- Brain Mapping, Luminescent Proteins, Mice, Inbred C57BL, Mice, Transgenic, Motor Cortex, Neural Pathways, Pyramidal Tracts, Somatosensory Cortex, Synapses, Thalamus
- Creator:
- Suter, Benjamin, Shepherd, Gordon M. G.
- Publisher:
- The Journal of Neuroscience, DigitalHub. Galter Health Sciences Library
- Language:
- English
- Date Created:
- 2015
- Rights:
- http://creativecommons.org/licenses/by/3.0/us/
- Resource Type:
- Journal Article
- Original Identifier:
- (PMID)25698734
- Title:
- A genuine layer 4 in motor cortex with prototypical synaptic circuit connectivity
- Original Bibliographic Citation:
- Chadderdon GL, Mohan A, Suter BA, Neymotin SA, Kerr CC, Francis JT, Shepherd GM, Lytton WW. (2014) Neural Comput. 26(7):1239-1262.
- Abstract:
- The motor cortex (M1) is classically considered an agranular area, lacking a distinct layer 4 (L4). Here, we tested the idea that M1, despite lacking a cytoarchitecturally visible L4, nevertheless possesses its equivalent in the form of excitatory neurons with inputoutput circuits like those of the L4 neurons in sensory areas. Consistent with this idea, we found that neurons located in a thin laminar zone at the L3/5A border in the forelimb area of mouse M1 have multiple L4-like synaptic connections: excitatory input from thalamus, largely unidirectional excitatory outputs to L2/3 pyramidal neurons, and relatively weak long-range corticocortical inputs and outputs. M1-L4 neurons were electrophysiologically diverse but morphologically uniform, with pyramidal-type dendritic arbors and locally ramifying axons, including branches extending into L2/3. Our findings therefore identify pyramidal neurons in M1 with the expected prototypical circuit properties of excitatory L4 neurons, and question the traditional assumption that motor cortex lacks this layer.
- Keyword:
- Neuroscience, Neocortex
- Subject: MESH:
- Action Potentials, Adenoviridae--genetics, Axons, Dendrites, Genetic Vectors, Mice, Motor Cortex, Pyramidal Cells, Synapses, Synaptic Potentials, Synaptic Transmission, Thalamus--physiology
- Creator:
- Suter, Benjamin, Shepherd, Gordon M G, Yamawaki, Naoki, Borges, Katharine Ellen Munckton
- Publisher:
- eLife, DigitalHub. Galter Health Sciences Library
- Language:
- English
- Date Created:
- 2014
- Rights:
- http://creativecommons.org/licenses/by/3.0/us/
- Resource Type:
- Journal Article
- Original Identifier:
- (PMID)25525751
- Title:
- Reduction of thalamic and cortical Ih by deletion of TRIP8b produces a mouse model of human absence epilepsy
- Original Bibliographic Citation:
- Heuermann RJ, Jaramillo TC, Ying SW, Suter BA, Lyman KA, Han Y, Lewis AS, Hampton TG, Shepherd GM, Goldstein PA, Chetkovich DM. (2016) Reduction of thalamic and cortical Ih by deletion of TRIP8b produces a mouse model of human absence epilepsy. Neurobiol Dis 85:81-92.
- Abstract:
- Absence seizures occur in several types of human epilepsy and result from widespread, synchronous feedback between the cortex and thalamus that produces brief episodes of loss of consciousness. Genetic rodent models have been invaluable for investigating the pathophysiological basis of these seizures. Here, we identify tetratricopeptide-containing Rab8b-interacting protein (TRIP8b) knockout mice as a new model of absence epilepsy, featuring spontaneous spike-wave discharges on electroencephalography (EEG) that are the electrographic hallmark of absence seizures. TRIP8b is an auxiliary subunit of the hyperpolarization-activated cyclic-nucleotide-gated (HCN) channels, which have previously been implicated in the pathogenesis of absence seizures. In contrast to mice lacking the pore-forming HCN channel subunit HCN2, TRIP8b knockout mice exhibited normal cardiac and motor function and a less severe seizure phenotype. Evaluating the circuit that underlies absence seizures, we found that TRIP8b knockout mice had significantly reduced HCN channel expression and function in thalamic-projecting cortical layer 5b neurons and thalamic relay neurons, but preserved function in inhibitory neurons of the reticular thalamic nucleus. Our results expand the known roles of TRIP8b and provide new insight into the region-specific functions of TRIP8b and HCN channels in constraining cortico-thalamo-cortical excitability.
- Keyword:
- Neuroscience, Neocortex, Trip8b protein, mouse
- Subject: MESH:
- Neocortex, Epilepsy, Absence, Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels, Models, Animal, Models, Neurological, Thalamus, Electroencephalography, Neural Pathways
- Creator:
- Suter, Benjamin, Chetkovich, Dane M, Heuerman, Robert J, Jaramillo, Thomas C, Lyman, Kyle A, Lewis, Alan S, Han, Ye, Shepherd, Gordon M G
- Publisher:
- Elsevier, DigitalHub. Galter Health Sciences Library
- Rights:
- http://creativecommons.org/licenses/by/3.0/us/
- Resource Type:
- Journal Article
- Original Identifier:
- (PMID)26459112
- Title:
- Cell-Specific Activity-Dependent Fractionation of Layer 2/35->5B Excitatory Signaling in Mouse Auditory Cortex
- Original Bibliographic Citation:
- Joshi A, Middleton JW, Anderson CT, Borges K, Suter BA, Shepherd GM, Tzounopoulos T. (2015) Cell-Specific Activity-Dependent Fractionation of Layer 2/35B Excitatory Signaling in Mouse Auditory Cortex. J Neurosci 35(7):3112-3123
- Abstract:
- Auditory cortex (AC) layer 5B (L5B) contains both corticocollicular neurons, a type of pyramidal-tract neuron projecting to the inferior colliculus, and corticocallosal neurons, a type of intratelencephalic neuron projecting to contralateral AC. Although it is known that these neuronal types have distinct roles in auditory processing and different response properties to sound, the synaptic and intrinsic mechanisms shaping their input-output functions remain less understood. Here, we recorded in brain slices of mouse AC from retrogradely labeled corticocollicular and neighboring corticocallosal neurons in L5B. Corticocollicular neurons had, on average, lower input resistance, greater hyperpolarization-activated current (Ih), depolarized resting membrane potential, faster action potentials, initial spike doublets, and less spike-frequency adaptation. In paired recordings between single L2/3 and labeled L5B neurons, the probabilities of connection, amplitude, latency, rise time, and decay time constant of the unitary EPSC were not different for L2/3corticocollicular and L2/3corticocallosal connections. However, short trains of unitary EPSCs showed no synaptic depression in L2/3corticocollicular connections, but substantial depression in L2/3corticocallosal connections. Synaptic potentials in L2/3corticocollicular connections decayed faster and showed less temporal summation, consistent with increased Ih in corticocollicular neurons, whereas synaptic potentials in L2/3corticocallosal connections showed more temporal summation. Extracellular L2/3 stimulation at two different rates resulted in spiking in L5B neurons; for corticocallosal neurons the spike rate was frequency dependent, but for corticocollicular neurons it was not. Together, these findings identify cell-specific intrinsic and synaptic mechanisms that divide intracortical synaptic excitation from L2/3 to L5B into two functionally distinct pathways with different input-output functions.
- Keyword:
- Neuroscience, Neocortex
- Subject: MESH:
- Auditory Cortex, Auditory Pathways, Mice, Inbred ICR, Excitatory Amino Acid Antagonists, Flavoproteins, GABA Antagonists, Inferior Colliculi, Models, Neurological, Neurons, Patch-Clamp Techniques, Pyridazines, Quinoxalines, Synaptic Potentials, Valine
- Creator:
- Suter, Benjamin, Shepherd, Gordon M G
- Publisher:
- Journal of Neuroscience, DigitalHub. Galter Health Sciences Library
- Language:
- English
- Date Created:
- 2014
- Rights:
- http://creativecommons.org/licenses/by/3.0/us/
- Resource Type:
- Journal Article
- Original Identifier:
- (PMID)25698747
- Title:
- Motor Cortex Microcircuit Simulation Based on Brain Activity Mapping
- Original Bibliographic Citation:
- Chadderdon GL, Mohan A, Suter BA, Neymotin SA, Kerr CC, Francis JT, Shepherd GM, Lytton WW. (2014) Motor Cortex Microcircuit Simulation Based on Brain Activity Mapping. Neural Comput. 26(7):1239-1262.
- Abstract:
- The deceptively simple laminar structure of neocortex belies the complexity of intra- and interlaminar connectivity. We developed a computational model based primarily on a unified set of brain activity mapping studies of mouse M1. The simulation consisted of 775 spiking neurons of 10 cell types with detailed population-to-population connectivity. Static analysis of connectivity with graph-theoretic tools revealed that the corticostriatal population showed strong centrality, suggesting that would provide a network hub. Subsequent dynamical analysis confirmed this observation, in addition to revealing network dynamics that cannot be readily predicted through analysis of the wiring diagram alone. Activation thresholds depended on the stimulated layer. Low stimulation produced transient activation, while stronger activation produced sustained oscillations where the threshold for sustained responses varied by layer: 13% in layer 2/3, 54% in layer 5A, 25% in layer 5B, and 17% in layer 6. The frequency and phase of the resulting oscillation also depended on stimulation layer. By demonstrating the effectiveness of combined static and dynamic analysis, our results show how static brain maps can be related to the results of brain activity mapping.
- Keyword:
- Neuroscience, Neocortex
- Subject: MESH:
- Brain Mapping, Mice, Computer Simulation, Models, Neurological, Motor Cortex, Neural Pathways, Neurons, Periodicity, Synapses
- Creator:
- Suter, Benjamin, Chadderdon, George L, Shepherd, Gordon M G
- Publisher:
- Massachusetts Institute of Technology, DigitalHub. Galter Health Sciences Library
- Language:
- English
- Date Created:
- 2013
- Rights:
- http://creativecommons.org/licenses/by/3.0/us/
- Resource Type:
- Journal Article
- Original Identifier:
- (PMID)24708371
- Title:
- Corticospinal-specific HCN expression in mouse motor cortex: Ih-dependent synaptic integration as a candidate microcircuit mechanism involved in motor control
- Original Bibliographic Citation:
- Sheets PL, Suter BA, Kiritani T, Chan CS, Surmeier DJ, Shepherd GM. (2011) Corticospinal-specific HCN expression in mouse motor cortex: Ih-dependent synaptic integration as a candidate microcircuit mechanism involved in motor control. J Neurophysiol 106(5):2216-2231.
- Abstract:
- Motor cortex is a key brain center involved in motor control in rodents and other mammals, but specific intracortical mechanisms at the microcircuit level are largely unknown. Neuronal expression of hyperpolarization-activated current (I(h)) is cell class specific throughout the nervous system, but in neocortex, where pyramidal neurons are classified in various ways, a systematic pattern of expression has not been identified. We tested whether I(h) is differentially expressed among projection classes of pyramidal neurons in mouse motor cortex. I(h) expression was high in corticospinal neurons and low in corticostriatal and corticocortical neurons, a pattern mirrored by mRNA levels for HCN1 and Trip8b subunits. Optical mapping experiments showed that I(h) attenuated glutamatergic responses evoked across the apical and basal dendritic arbors of corticospinal but not corticostriatal neurons. Due to I(h), corticospinal neurons resonated, with a broad peak at 4 Hz, and were selectively modulated by -adrenergic stimulation. I(h) reduced the summation of short trains of artificial excitatory postsynaptic potentials (EPSPs) injected at the soma, and similar effects were observed for short trains of actual EPSPs evoked from layer 2/3 neurons. I(h) narrowed the coincidence detection window for EPSPs arriving from separate layer 2/3 inputs, indicating that the dampening effect of I(h) extended to spatially disperse inputs. To test the role of corticospinal I(h) in transforming EPSPs into action potentials, we transfected layer 2/3 pyramidal neurons with channelrhodopsin-2 and used rapid photostimulation across multiple sites to synaptically drive spiking activity in postsynaptic neurons. Blocking I(h) increased layer 2/3-driven spiking in corticospinal but not corticostriatal neurons. Our results imply that I(h)-dependent synaptic integration in corticospinal neurons constitutes an intracortical control mechanism, regulating the efficacy with which local activity in motor cortex is transferred to downstream circuits in the spinal cord. We speculate that modulation of I(h) in corticospinal neurons could provide a microcircuit-level mechanism involved in translating action planning into action execution.
- Keyword:
- Neuroscience, Neocortex
- Subject: MESH:
- Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels, Motor Cortex, Mice, Inbred C57BL, Excitatory Postsynaptic Potentials
- Creator:
- Suter, Benjamin, Sheets, Patrick L., Kiritani, Taro, Chan, Savio, Surmeier, Dalton James, Shepherd, Gordon M G
- Publisher:
- American Physiological Society, DigitalHub. Galter Health Sciences Library
- Language:
- English
- Date Created:
- 2011
- Rights:
- http://creativecommons.org/licenses/by/3.0/us/
- Resource Type:
- Journal Article
- Original Identifier:
- (PMID)21795621
- Title:
- Tempering Allorecognition to Induce Transplant Tolerance With Chemically Modified Apoptotic Donor Cells
- Original Bibliographic Citation:
- McCarthy DP, Bryant J, Galvin JP, Miller SD, Luo, X (2015) Tempering Allorecognition to Induce Transplant Tolerance With Chemically Modified Apoptotic Donor Cells. Am J Transplant 15(6):1475-1483.
- Abstract:
- The development of organ transplantation as a therapy for end-stage organ failure is among the most significant achievements of 20th century medicine, but chronic rejection remains a barrier to achieving long-term success. Current therapeutic regimens consist of immunosuppressive drugs that are efficient at delaying rejection but are associated with significant risks such as opportunistic infections, toxicity, and malignancy. Thus, the induction of specific immune tolerance to transplant antigens is the coveted aim of researchers. The use of 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide (ECDI)-treated, autoantigen-coupled syngeneic leukocytes has been developed as a specific immunotherapy in preclinical models of autoimmunity and is currently in a phase II clinical trial for the treatment of multiple sclerosis. In this review, we discuss the use of allogeneic ECDI-treated apoptotic donor leukocytes (allo-ECDI-SP) as a strategy for inducing antigen-specific tolerance in allogeneic transplantation. Allo-ECDI-SP therapy induces long-term systemic immune tolerance to transplant antigens by subverting alloimmune recognition and exploiting apoptotic cell uptake pathways to recapitulate innate mechanisms of peripheral tolerance. Lastly, we discuss potential indications and challenges for transitioning allo-ECDI-SP therapy into clinical practice.
- Keyword:
- Tolerance, Transplant, Apoptotic cells
- Subject: MESH:
- Transplantation Tolerance, Transplantation Immunology, Transplantation, Homologous, Histocompatibility Antigens
- Creator:
- Galvin, John P, Miller, Stephen D, Luo, Xunrong, McCarthy, D. P., Bryant, J.
- Publisher:
- DigitalHub. Galter Health Sciences Library
- Language:
- English
- Date Created:
- 2015
- Rights:
- http://creativecommons.org/licenses/by/3.0/us/
- Resource Type:
- Review
- Title:
- Apoptosis Induced by Granzyme B-Glycosaminoglycan Complexes: Implications for Granule-Mediated Apoptosis In Vivo
- Original Bibliographic Citation:
- Galvin JP, Spaeny-Dekking LH, Wang B, Seth P, Hack CE, Froelich CJ. (1999) Apoptosis Induced by Granzyme B-Glycosaminoglycan Complexes: Implications for Granule-Mediated Apoptosis In Vivo. J Immunol 162(9):5345-5350.
- Abstract:
- Lymphocyte granule-mediated apoptosis occurs by perforin-mediated intracellular delivery of granule-associated serine proteases (granzymes). A granule-associated proteoglycan, namely serglycin, that contains chondroitin 4-sulfate (CS) glycosaminoglycans is present in the granules of cytotoxic cells. Serglycin acts as scaffold for packaging the positively charged granzymes and probably chaperones the proteases secreted extracellularly. To learn how the interaction of granzyme B (GrB) with serglycin might influence the apoptotic potential of this proteases, we have evaluated a model system where desalted CS is combined with isolated human granzyme. CS-GrB complexes were very stable, remaining undissociated in salt concentrations upwards to 500 mM (pH 7.4). On the basis of a capture enzyme immunoassay that accurately detects GrB, equivalent amounts of active free and CS-GrB, delivered by perforin or adenovirus, efficiently induced apoptosis in Jurkat cells and produced a similar time-dependent increase in caspase-3-like activity. CS-GrB processed isolated caspases-3 and -7 less efficiently than free granzyme. However, when added to cytosolic extracts, rates of processing were nearly equivalent for the two forms, suggesting cationic GrB may nonspecifically bind cytosolic proteins, leading to reduce proteolytic activity. Finally, GrB was found to be exocytosed from lymphocyte-activated killer cells as a neutral, high macromolecular weight complex, which possessed apoptotic activity. Collectively, the results indicate that neutral, high m.w. GrB has the capacity to induce cell death and will be useful to study the mechanism of cytotoxic cell-mediated apoptosis in vitro.
- Keyword:
- Apoptosis, Granzyme
- Subject: MESH:
- Apoptosis, Granzymes, Glycosaminoglycans
- Creator:
- Galvin, John P, Froelich, Christopher J, Wang, Baikun, Spaeny-Dekking, Liesbeth H. A., Seth, Prem K, Hack, C. EriK
- Publisher:
- American Association of Immunologists, Inc., DigitalHub. Galter Health Sciences Library
- Language:
- English
- Date Created:
- 1999
- Rights:
- http://creativecommons.org/licenses/by/3.0/us/
- Resource Type:
- Journal Article
- Original Identifier:
- (PMID)10228010
- Title:
- Regulation of the kinase RSK1 by arsenic trioxide and generation of antileukemic responses
- Original Bibliographic Citation:
- Galvin JP, Altman JK, Szilard A, Goussetis DJ, Vakana E, Sassano A, Platanias LC. (2013) Cancer Biol Ther 14:411-416.
- Abstract:
- Arsenic Trioxide (AsO) is one of the most effective agents in the treatment of acute promyelocytic leukemia (APL), but has no significant efficacy in other forms of AML. The mechanisms of relative resistance of non-APL cells are not well understood, but emerging evidence suggests that activation of negative feedback regulatory loops and pathways contributes to such resistance. We provide evidence that a signaling cascade involving the kinase RSK1 is engaged in a negative feedback manner during arsenic-treatment of cells and exhibits regulatory effects on growth and survival of AML cells in response to treatment with AsO. Our data demonstrate that pharmacological inhibition or molecular disruption of expression of RSK1 enhances AsO-dependent apoptosis and/or growth inhibition of AML cells. Importantly, combination of a pharmacological inhibitor of RSK and AsO results in enhanced suppression of primary AML leukemic progenitors. Altogether, our findings suggest an important regulatory role for RSK1 in the generation of the effects of AsO in AML cells. They also raise the potential of RSK1 targeting in combination with AsO as a novel approach to promote antileukemic responses.
- Keyword:
- Leukemia, Arsenic Trioxide, RSK1
- Subject: MESH:
- Arsenicals--pharmacology, Leukemia, Myeloid, Acute, Ribosomal Protein S6 Kinases, 90-kDa
- Creator:
- Galvin, John P, Platanias, Leonidas C, Altman, Jessica K, Szilard, Amy, Goussetis, Dennis J., Vakana, Eliza, Sassano, Antonella
- Publisher:
- Landes Bioscience, DigitalHub. Galter Health Sciences Library
- Language:
- English
- Date Created:
- 2013
- Rights:
- http://creativecommons.org/licenses/by/3.0/us/
- Resource Type:
- Journal Article
- Original Identifier:
- (PMID)23377826