{"id":{"repo_id":"mit","oai_identifier":"oai:dspace.mit.edu:1721.1/106067"},"canonical_url":"https://search.dev.ndltd.org/etd/mit/oai:dspace.mit.edu:1721.1/106067","repository":{"repo_id":"mit","name":"MIT","base_url":"https://dspace.mit.edu/oai/request"},"display":{"title":"Mesoscale activated states gate spiking in the awake brain","abstract":"Neuronal action potentials ('spikes') are thought to be the fundamental units of information in the brain, hence the ability to record them and to understand their genesis is crucial to our comprehension of the biological underpinnings of our thoughts, memories, and feelings. Over the past several decades an extensive body of work has focused on the mechanisms and timescales over which neurons integrate inputs toward spike threshold. However, most of the work has been carried out in vitro or in silico, and our understanding of what underlies the generation of spike patterns in the awake brain has remained limited. Current models emphasize either seconds-scale global states shared by most neurons in a network, or the fast input integration occurring in single neurons over the few milliseconds preceding spiking, but it's not known whether these represent just the extremes of a continuum. Combining a virtual reality environment with an optimized robotic system for intracellular recordings we therefore analyzed the subthreshold dynamics leading to spiking in a variety of network and behavioral states in the hippocampus, a region known to be involved in spatial navigation, learning and memory, as well as in a model neocortical region, the primary somatosensory cortex. We discovered that the majority of spikes are in fact preceded not only by a fast, monotonic rise in voltage over a few milliseconds, consistent with fast input integration within a neuron, but also by a prolonged, gradual (tens to hundreds of ms) depolarization from baseline, which appeared to exert a gating function on subsequent inputs. Unlike the fast voltage rises, these gradual voltage rises are shared across some, but not all, neurons in the network. We propose that the gradual rises in membrane voltage constitute a novel form of activated state, intermediate both in timescale and in what proportion of neurons participate. By gating a neuron's ability to respond to subsequent inputs, these network-mediated intermediate, or mesoscale, activated states could play a key role in phenomena such as cell ensemble formation, gain modulation and selective attention.","abstract_html":"Neuronal action potentials ('spikes') are thought to be the fundamental units of information in the brain, hence the ability to record them and to understand their genesis is crucial to our comprehension of the biological underpinnings of our thoughts, memories, and feelings. Over the past several decades an extensive body of work has focused on the mechanisms and timescales over which neurons integrate inputs toward spike threshold. However, most of the work has been carried out in vitro or in silico, and our understanding of what underlies the generation of spike patterns in the awake brain has remained limited. Current models emphasize either seconds-scale global states shared by most neurons in a network, or the fast input integration occurring in single neurons over the few milliseconds preceding spiking, but it's not known whether these represent just the extremes of a continuum. Combining a virtual reality environment with an optimized robotic system for intracellular recordings we therefore analyzed the subthreshold dynamics leading to spiking in a variety of network and behavioral states in the hippocampus, a region known to be involved in spatial navigation, learning and memory, as well as in a model neocortical region, the primary somatosensory cortex. We discovered that the majority of spikes are in fact preceded not only by a fast, monotonic rise in voltage over a few milliseconds, consistent with fast input integration within a neuron, but also by a prolonged, gradual (tens to hundreds of ms) depolarization from baseline, which appeared to exert a gating function on subsequent inputs. Unlike the fast voltage rises, these gradual voltage rises are shared across some, but not all, neurons in the network. We propose that the gradual rises in membrane voltage constitute a novel form of activated state, intermediate both in timescale and in what proportion of neurons participate. By gating a neuron's ability to respond to subsequent inputs, these network-mediated intermediate, or mesoscale, activated states could play a key role in phenomena such as cell ensemble formation, gain modulation and selective attention.","abstract_has_math":false,"creators":["Talei Franzesi, Giovanni"],"institution":"Massachusetts Institute of Technology","degree_name":null,"degree_level":null,"degree_discipline":null,"degree_department":"Program in Media Arts and Sciences (Massachusetts Institute of Technology)","school":null,"contributors":[],"advisors":["Edward S. Boyden."],"committee_chairs":[],"committee_members":[],"year":2016,"date_issued":"2016","date_published":"2016","updated_at":"2026-07-22T22:21:25Z","subjects":["Program in Media Arts and Sciences ()"],"languages":["eng"],"rights":["M.I.T. theses are protected by copyright. They may be viewed from this source for any purpose, but reproduction or distribution in any format is prohibited without written permission. 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Current models emphasize either seconds-scale global states shared by most neurons in a network, or the fast input integration occurring in single neurons over the few milliseconds preceding spiking, but it's not known whether these represent just the extremes of a continuum. Combining a virtual reality environment with an optimized robotic system for intracellular recordings we therefore analyzed the subthreshold dynamics leading to spiking in a variety of network and behavioral states in the hippocampus, a region known to be involved in spatial navigation, learning and memory, as well as in a model neocortical region, the primary somatosensory cortex. We discovered that the majority of spikes are in fact preceded not only by a fast, monotonic rise in voltage over a few milliseconds, consistent with fast input integration within a neuron, but also by a prolonged, gradual (tens to hundreds of ms) depolarization from baseline, which appeared to exert a gating function on subsequent inputs. Unlike the fast voltage rises, these gradual voltage rises are shared across some, but not all, neurons in the network. We propose that the gradual rises in membrane voltage constitute a novel form of activated state, intermediate both in timescale and in what proportion of neurons participate. By gating a neuron's ability to respond to subsequent inputs, these network-mediated intermediate, or mesoscale, activated states could play a key role in phenomena such as cell ensemble formation, gain modulation and selective attention."]},{"key":"dc:description.degree","label":"Dc Description Degree","values":["Ph. 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Current models emphasize either seconds-scale global states shared by most neurons in a network, or the fast input integration occurring in single neurons over the few milliseconds preceding spiking, but it's not known whether these represent just the extremes of a continuum. Combining a virtual reality environment with an optimized robotic system for intracellular recordings we therefore analyzed the subthreshold dynamics leading to spiking in a variety of network and behavioral states in the hippocampus, a region known to be involved in spatial navigation, learning and memory, as well as in a model neocortical region, the primary somatosensory cortex. We discovered that the majority of spikes are in fact preceded not only by a fast, monotonic rise in voltage over a few milliseconds, consistent with fast input integration within a neuron, but also by a prolonged, gradual (tens to hundreds of ms) depolarization from baseline, which appeared to exert a gating function on subsequent inputs. Unlike the fast voltage rises, these gradual voltage rises are shared across some, but not all, neurons in the network. We propose that the gradual rises in membrane voltage constitute a novel form of activated state, intermediate both in timescale and in what proportion of neurons participate. By gating a neuron's ability to respond to subsequent inputs, these network-mediated intermediate, or mesoscale, activated states could play a key role in phenomena such as cell ensemble formation, gain modulation and selective attention."],"dc:description.degree":["Ph. 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