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Elucidating the Neuronal Circuits of the Somatosensory System
Elucidating the Neuronal Circuits of the Somatosensory System
Elucidating the Neuronal Circuits of the Somatosensory System

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자료유형  
 학위논문 서양
최종처리일시  
20250211151005
ISBN  
9798381954388
DDC  
616
저자명  
Lawlor, Kristen J.
서명/저자  
Elucidating the Neuronal Circuits of the Somatosensory System
발행사항  
[Sl] : Columbia University, 2024
발행사항  
Ann Arbor : ProQuest Dissertations & Theses, 2024
형태사항  
169 p
주기사항  
Source: Dissertations Abstracts International, Volume: 85-09, Section: B.
주기사항  
Advisor: Sajda, Paul.
학위논문주기  
Thesis (Ph.D.)--Columbia University, 2024.
초록/해제  
요약As animals explore and interact with their surroundings, information about their environment is constantly processed from sensory stimuli into perception. This information informs their behavior, decision-making, and understanding of their world. Information processing and perception have long been thought to be modulated by the behavior state of the animal (Cano et al. 2006; Niell and Stryker 2010; Polack et al. 2013; Poulet & Petersen, 2008; Briggs 2013, Scholvinck et al. 2015). Previous research has shown that behavior state strongly correlates with perceptual performance in a sensory discrimination task in rodents (McGinley et al. 2015, Schriver et al., 2018). However, the neural correlates behind this modulation of perception, information processing, and behavioral performance are not yet fully understood.The first part of this work investigates the relationship between cell-type specific spontaneous cortical activity and behavior state as defined by pupil-linked arousal. Spontaneous activity is essential in understanding the link between behavior state and information processing as it serves as the baseline state of activity prior to processing any stimuli information. Within the sensory cortices, excitatory and inhibitory neurons work in unison to dictate network activity. Three main classes of cortical inhibitory neurons are somatostatin-expressing neurons (SST), vasointestinal peptide-expressing neurons (VIP), and parvalbumin-expressing neurons (PV). These four cell types comprise the VIP disinhibitory circuit, in which VIP neurons disinhibit excitatory neurons by inhibiting PV and SST neurons. PV and SST neurons directly inhibit excitatory cells, so by suppressing their activity VIP neurons indirectly disinhibit excitatory cells. This circuit is a vitally important system used to modify excitatory activity in all cortical regions. The spontaneous activity of excitatory neurons and three classes of inhibitory neurons (somatostatin-expressing neurons (SST), vasointestinal peptide-expressing neurons (VIP), and parvalbumin-expressing neurons (PV)) was individually examined in this study.To visualize in-vivo spontaneous cortical activity, a genetically encoded calcium indicator (GCaMP) was expressed in the somatosensory cortex, and the population-level neural activity was imaged using fiber photometry. Despite the relationship between these neurons as defined by the VIP disinhibitory circuit, the spontaneous activity of excitatory, VIP, PV, and SST neurons was found to positively correlate with pupil size for all of these neuron types. This supports the theory that VIP and other interneuron types may be active in various functions, not just the disinhibition of excitatory cells. Pupil-evoked activity, or spontaneous activity during highly aroused states, was also found to positively correlate with pupil size for all cell types and had the strongest correlation for all correlation types. Therefore, pupil-linked arousal level relates to the increased activity of both excitatory and inhibitory cortical cells.While the first chapter focuses on spontaneous activity, the second focuses on stimulus-evoked activity. Stimulus-evoked activity in the somatosensory pathway can be caused by both internally generated stimuli and external stimuli. In the first step of sensory processing, the sensory receptors cannot distinguish between these two types of stimuli. However, the differentiation between the two is necessary in order to distinguish self from non-self. The motor-related timing signals that influence sensory processing and enable distinction between internally generated and external stimuli is termed corollary discharge. Where and how the mechanism of corollary discharge occurs in the somatosensory system is not well understood.To investigate corollary discharge in the somatosensory system, the neural activity in the somatosensory cortex was analyzed during internally generated stimuli and during delivery of external stimuli. More specifically, the activity in the vibrissa somatosensory cortex of rodents during self-induced whisking and during delivery of an air puff to the whiskers was examined. In the primary and secondary somatosensory cortex, excitatory activity was inhibited just prior to whisking and suppressed to a lower level during whisking in comparison to the activity level during air puff delivery. The three main classes of inhibitory neurons were studied to explore the possibility of local inhibition causing this suppression of the excitatory signal during whisking. VIP, PV and SST neurons all exhibited a similar pre-whisking inhibition and suppression of activity during whisking, eliminating the possibility of their role in pre-whisking inhibition and whisking activity suppression. Other regions involved in the somatosensory pathway and sensorimotor processing, such as the thalamus and motor cortex, were also found to not contribute to pre-whisking inhibition or whisking activity suppression as they were also found to exhibit the same phenomenon.After ruling out cortical inhibitory neurons and somatosensory regions in the involvement of corollary discharge, external higher-order regions were investigated. Previous studies on the sources of corollary discharge in the cerebellum have shown corollary discharge signals originate from coordination of several different higher-order brain regions (Person A., 2019). To determine these potential regions for somatosensory corollary discharge, viral tracing vectors were used to locate regions with long-range inhibitory projections to the somatosensory cortex. The globus pallidus (GP) was first investigated due to its role in voluntary movement and projections to the frontal cortex (Saunders et al. 2015). However, no inhibitory projections from the GP to the somatosensory cortex were found. The striatum, which is mainly GABAergic (and therefore inhibitory), also seemed to be a likely candidate. Preliminary tracing results suggest the striatum does have inhibitory projections to the somatosensory cortex. Further studies of both retrograde and anterograde tracing must be performed to confirm this finding. Nonetheless, the evidence of corollary discharge as seen through pre-whisking inhibition and the suppression of activity during whisking in S1, S2, thalamus, and motor cortex is a novel finding and opens up many avenues for further research.
일반주제명  
Neurosciences
일반주제명  
Physiology
일반주제명  
Medical imaging
일반주제명  
Psychobiology
일반주제명  
Behavioral sciences
키워드  
Somatosensory system
키워드  
Neuronal circuits
키워드  
Corollary discharge
키워드  
Parvalbumin-expressing neurons
키워드  
Somatostatin-expressing neurons
기타저자  
Columbia University Biomedical Engineering
기본자료저록  
Dissertations Abstracts International. 85-09B.
전자적 위치 및 접속  
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■1001  ▼aLawlor,  Kristen  J.
■24510▼aElucidating  the  Neuronal  Circuits  of  the  Somatosensory  System
■260    ▼a[Sl]▼bColumbia  University▼c2024
■260  1▼aAnn  Arbor▼bProQuest  Dissertations  &  Theses▼c2024
■300    ▼a169  p
■500    ▼aSource:  Dissertations  Abstracts  International,  Volume:  85-09,  Section:  B.
■500    ▼aAdvisor:  Sajda,  Paul.
■5021  ▼aThesis  (Ph.D.)--Columbia  University,  2024.
■520    ▼aAs  animals  explore  and  interact  with  their  surroundings,  information  about  their  environment  is  constantly  processed  from  sensory  stimuli  into  perception.  This  information  informs  their  behavior,  decision-making,  and  understanding  of  their  world.  Information  processing  and  perception  have  long  been  thought  to  be  modulated  by  the  behavior  state  of  the  animal  (Cano  et  al.  2006;  Niell  and  Stryker  2010;  Polack  et  al.  2013;  Poulet  &  Petersen,  2008;  Briggs  2013,  Scholvinck  et  al.  2015).  Previous  research  has  shown  that  behavior  state  strongly  correlates  with  perceptual  performance  in  a  sensory  discrimination  task  in  rodents  (McGinley  et  al.  2015,  Schriver  et  al.,  2018).  However,  the  neural  correlates  behind  this  modulation  of  perception,  information  processing,  and  behavioral  performance  are  not  yet  fully  understood.The  first  part  of  this  work  investigates  the  relationship  between  cell-type  specific  spontaneous  cortical  activity  and  behavior  state  as  defined  by  pupil-linked  arousal.  Spontaneous  activity  is  essential  in  understanding  the  link  between  behavior  state  and  information  processing  as  it  serves  as  the  baseline  state  of  activity  prior  to  processing  any  stimuli  information.  Within  the  sensory  cortices,  excitatory  and  inhibitory  neurons  work  in  unison  to  dictate  network  activity.  Three  main  classes  of  cortical  inhibitory  neurons  are  somatostatin-expressing  neurons  (SST),  vasointestinal  peptide-expressing  neurons  (VIP),  and  parvalbumin-expressing  neurons  (PV).  These  four  cell  types  comprise  the  VIP  disinhibitory  circuit,  in  which  VIP  neurons  disinhibit  excitatory  neurons  by  inhibiting  PV  and  SST  neurons.  PV  and  SST  neurons  directly  inhibit  excitatory  cells,  so  by  suppressing  their  activity  VIP  neurons  indirectly  disinhibit  excitatory  cells.  This  circuit  is  a  vitally  important  system  used  to  modify  excitatory  activity  in  all  cortical  regions.  The  spontaneous  activity  of  excitatory  neurons  and  three  classes  of  inhibitory  neurons  (somatostatin-expressing  neurons  (SST),  vasointestinal  peptide-expressing  neurons  (VIP),  and  parvalbumin-expressing  neurons  (PV))  was  individually  examined  in  this  study.To  visualize  in-vivo  spontaneous  cortical  activity,  a  genetically  encoded  calcium  indicator  (GCaMP)  was  expressed  in  the  somatosensory  cortex,  and  the  population-level  neural  activity  was  imaged  using  fiber  photometry.  Despite  the  relationship  between  these  neurons  as  defined  by  the  VIP  disinhibitory  circuit,  the  spontaneous  activity  of  excitatory,  VIP,  PV,  and  SST  neurons  was  found  to  positively  correlate  with  pupil  size  for  all  of  these  neuron  types.  This  supports  the  theory  that  VIP  and  other  interneuron  types  may  be  active  in  various  functions,  not  just  the  disinhibition  of  excitatory  cells.  Pupil-evoked  activity,  or  spontaneous  activity  during  highly  aroused  states,  was  also  found  to  positively  correlate  with  pupil  size  for  all  cell  types  and  had  the  strongest  correlation  for  all  correlation  types.  Therefore,  pupil-linked  arousal  level  relates  to  the  increased  activity  of  both  excitatory  and  inhibitory  cortical  cells.While  the  first  chapter  focuses  on  spontaneous  activity,  the  second  focuses  on  stimulus-evoked  activity.  Stimulus-evoked  activity  in  the  somatosensory  pathway  can  be  caused  by  both  internally  generated  stimuli  and  external  stimuli.  In  the  first  step  of  sensory  processing,  the  sensory  receptors  cannot  distinguish  between  these  two  types  of  stimuli.  However,  the  differentiation  between  the  two  is  necessary  in  order  to  distinguish  self  from  non-self.  The  motor-related  timing  signals  that  influence  sensory  processing  and  enable  distinction  between  internally  generated  and  external  stimuli  is  termed  corollary  discharge.  Where  and  how  the  mechanism  of  corollary  discharge  occurs  in  the  somatosensory  system  is  not  well  understood.To  investigate  corollary  discharge  in  the  somatosensory  system,  the  neural  activity  in  the  somatosensory  cortex  was  analyzed  during  internally  generated  stimuli  and  during  delivery  of  external  stimuli.  More  specifically,  the  activity  in  the  vibrissa  somatosensory  cortex  of  rodents  during  self-induced  whisking  and  during  delivery  of  an  air  puff  to  the  whiskers  was  examined.  In  the  primary  and  secondary  somatosensory  cortex,  excitatory  activity  was  inhibited  just  prior  to  whisking  and  suppressed  to  a  lower  level  during  whisking  in  comparison  to  the  activity  level  during  air  puff  delivery.  The  three  main  classes  of  inhibitory  neurons  were  studied  to  explore  the  possibility  of  local  inhibition  causing  this  suppression  of  the  excitatory  signal  during  whisking.  VIP,  PV  and  SST  neurons  all  exhibited  a  similar  pre-whisking  inhibition  and  suppression  of  activity  during  whisking,  eliminating  the  possibility  of  their  role  in  pre-whisking  inhibition  and  whisking  activity  suppression.  Other  regions  involved  in  the  somatosensory  pathway  and  sensorimotor  processing,  such  as  the  thalamus  and  motor  cortex,  were  also  found  to  not  contribute  to  pre-whisking  inhibition  or  whisking  activity  suppression  as  they  were  also  found  to  exhibit  the  same  phenomenon.After  ruling  out  cortical  inhibitory  neurons  and  somatosensory  regions  in  the  involvement  of  corollary  discharge,  external  higher-order  regions  were  investigated.  Previous  studies  on  the  sources  of  corollary  discharge  in  the  cerebellum  have  shown  corollary  discharge  signals  originate  from  coordination  of  several  different  higher-order  brain  regions  (Person  A.,  2019).  To  determine  these  potential  regions  for  somatosensory  corollary  discharge,  viral  tracing  vectors  were  used  to  locate  regions  with  long-range  inhibitory  projections  to  the  somatosensory  cortex.  The  globus  pallidus  (GP)  was  first  investigated  due  to  its  role  in  voluntary  movement  and  projections  to  the  frontal  cortex  (Saunders  et  al.  2015).  However,  no  inhibitory  projections  from  the  GP  to  the  somatosensory  cortex  were  found.  The  striatum,  which  is  mainly  GABAergic  (and  therefore  inhibitory),  also  seemed  to  be  a  likely  candidate.  Preliminary  tracing  results  suggest  the  striatum  does  have  inhibitory  projections  to  the  somatosensory  cortex.  Further  studies  of  both  retrograde  and  anterograde  tracing  must  be  performed  to  confirm  this  finding.  Nonetheless,  the  evidence  of  corollary  discharge  as  seen  through  pre-whisking  inhibition  and  the  suppression  of  activity  during  whisking  in  S1,  S2,  thalamus,  and  motor  cortex  is  a  novel  finding  and  opens  up  many  avenues  for  further  research.
■590    ▼aSchool  code:  0054.
■650  4▼aNeurosciences
■650  4▼aPhysiology
■650  4▼aMedical  imaging
■650  4▼aPsychobiology
■650  4▼aBehavioral  sciences
■653    ▼aSomatosensory  system
■653    ▼aNeuronal  circuits
■653    ▼aCorollary  discharge
■653    ▼aParvalbumin-expressing  neurons
■653    ▼aSomatostatin-expressing  neurons
■690    ▼a0317
■690    ▼a0574
■690    ▼a0349
■690    ▼a0602
■690    ▼a0719
■71020▼aColumbia  University▼bBiomedical  Engineering.
■7730  ▼tDissertations  Abstracts  International▼g85-09B.
■790    ▼a0054
■791    ▼aPh.D.
■792    ▼a2024
■793    ▼aEnglish
■85640▼uhttp://www.riss.kr/pdu/ddodLink.do?id=T17160362▼nKERIS▼z이  자료의  원문은  한국교육학술정보원에서  제공합니다.

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