{"created":"2023-06-20T13:22:06.436101+00:00","id":2513,"links":{},"metadata":{"_buckets":{"deposit":"10d279e1-fee1-4d22-ab8d-af5e82a63bd7"},"_deposit":{"created_by":21,"id":"2513","owners":[21],"pid":{"revision_id":0,"type":"depid","value":"2513"},"status":"published"},"_oai":{"id":"oai:ir.soken.ac.jp:00002513","sets":["2:430:22"]},"author_link":["0","0","0"],"item_1_creator_2":{"attribute_name":"著者名","attribute_type":"creator","attribute_value_mlt":[{"creatorNames":[{"creatorName":"中川, 直"}],"nameIdentifiers":[{}]}]},"item_1_creator_3":{"attribute_name":"フリガナ","attribute_type":"creator","attribute_value_mlt":[{"creatorNames":[{"creatorName":"ナカガワ　, ナオ"}],"nameIdentifiers":[{}]}]},"item_1_date_granted_11":{"attribute_name":"学位授与年月日","attribute_value_mlt":[{"subitem_dategranted":"2011-03-24"}]},"item_1_degree_grantor_5":{"attribute_name":"学位授与機関","attribute_value_mlt":[{"subitem_degreegrantor":[{"subitem_degreegrantor_name":"総合研究大学院大学"}]}]},"item_1_degree_name_6":{"attribute_name":"学位名","attribute_value_mlt":[{"subitem_degreename":"博士（理学）"}]},"item_1_description_12":{"attribute_name":"要旨","attribute_value_mlt":[{"subitem_description":"Pyramidal neurons in the cerebral cortex are principal neurons projecting their outputs to various brain areas. A salient feature of pyramidal neurons is their distinct apical and basal dendrites, which protrude from the apex and the basal of the soma. These neurons receive excitatory inputs from various cells on their numerous dendritic spines, which amount to several thousands. The elucidation of signal integration mechanisms in the neuron with numerous inputs is pivotal to the understanding of cortical information processing. Neuronal connectivity in visual cortex has been intensively studied and specific neuronal connections are considerably unraveled. For example, layer 2/3 pyramidal neurons, sending output signals to other cortex, receive various inputs including those from outside of the cortex, such as the thalamus and other cortex, as well as those from nearby cortical cells in layer 2/3, 4 and 5. It is known that inputs from the higher-order cortex target the distal part of apical dendrites. Recent studies have clearly demonstrated that specific and non-specific thalamic neurons send their outputs mainly on the basal and distal apical dendrites, respectively. However, the spatial distribution of inputs from nearby cortical neurons on dendrites is not well resolved yet, mainly due to technical difficulties. Because apical and basal dendrites in pyramidal cells are separated by the soma which integrates signals sent from synaptic sites that distributed broadly on dendrites, synaptic inputs on apical and basal dendrites may contribute differently to the signal integration at the cellular level.<br/>I attempted to determine whether postsynaptic responses in pyramidal neurons in the lower part of layer 2/3 (layer 3) are mediated by inputs from nearby cortical cells on apical or basal dendrites in rat visual cortex. There are no excitatory synapses on the soma and the proximal part of apical dendrites. This spatial arrangement of the excitatory synapses was utilized to resolve this issue. I conducted dual whole-cell voltage-clamp recordings from the dendrite and the soma of the same pyramidal cell. I placed one patch pipette on the primary apical dendrite and the other on the soma, so that there were no excitatory synapses between the two pipettes. In this condition, it is expected that excitatory postsynaptic currents (EPSCs) recorded from the dendrite would be larger than those recorded from the soma if the excitatory inputs impinge on the apical dendrites, while opposite results would be obtained if the excitatory inputs impinge on the basal dendrites.<br/>In order to investigate this issue, I first analyzed inward currents evoked by focal photostimulation of the apical and basal dendrites with glutamate uncaging in the presence of the Na+ channel blocker tetrodotoxin (TTX). The relationship between the direct responses recorded by the two electrodes was consistent with our expectations. I attempted to separate miniature EPSCs (mEPSCs) into those mediated by inputs to the apical and basal dendrites. In the graph plotting the amplitude of responses recoded from the dendrite against the amplitude of the responses recorded from the soma, mEPSCs were clearly separated into two groups. One group of mEPSCs was distributed along a linear regression line with a slope larger than 1, while the other group was distributed along another line with a slope smaller than 1. Direct responses evoked by the stimulation of apical and basal dendrites of the cell were exactly distributed along the former and latter regression lines, respectively, suggesting that it is possible to determine whether individual mEPSCs originated from apical or basal dendrites based on the amplitude ratio of responses recorded simultaneously.<br/>I computed a frequency distribution of the log ratios of the dendritic response amplitude to the somatic response amplitude (logR), to promote this identification of the mEPSC origin. The logR distribution for mEPSCs was well fitted by a sum of two Gaussian curves, which peaked at a negative and a positive logR value, and clearly separated by a trough at around 0 between the two peaks. The direct responses evoked by apical and basal dendrites were distributed around either the positive or negative peak. This clear dichotomy supports the view that a logR larger or smaller than the value at the trough reliably indicates apical and basal dendritic origin, respectively.<br/>This method seemed applicable to the analysis of evoked EPSCs (eEPSCs), because the frequency distribution for spontaneous EPSCs (sEPSCs) recorded in a normal solution without TTX was also fitted with a sum of two Gaussian curves exactly as the distribution for mEPSCs. This suggests that sEPSCs were mostly mediated by inputs to either apical or basal dendrites, just like the mEPSCs. I analyzed the eEPSCs by activating cortical neurons with laser-scanning photostimulation. In most of the frequency distribution of logR for the eEPSCs, a large negative peak was clearly seen, while the positive peak was vague and small, and some of the eEPSC were located around 0. This suggests that cortical inputs target far more basal than apical dendrites. In addition, some of inputs likely target apical and basal dendrites together.<br/>The number of eEPSCs derived from one experiment was not enough to reliably quantify the proportion of eEPSCs mediated by inputs from each layer on the basal or apical dendrites alone, or common inputs to both apical and basal dendrites. Therefore, I normalized the frequency distribution of logR so that the negative and positive peaks were converted to -1 and +1, respectively, and then constructed a pooled distribution for all of the tested cells. The pooled distribution was fitted with a sum of two Gaussian curves with the peaks at -1 and 1 using eEPSCs with abscissa values smaller than -1 or larger than 1, because these eEPSCs are considered to be mediated by basal or apical dendrites alone. I estimated the percentage of apical and basal eEPSCs from the fitting curve with negative and positive values, respectively, and then that of the eEPSCs due to common inputs from the difference between the distribution and the fitting curve.<br/>The majority of inputs targeted either the basal or the apical dendrite alone, while the remaining minor inputs impinged on both dendrites. There were far more basal eEPSCs (66%) than apical eEPSCs (20%). The proportion of eEPSCs with common inputs (14%) was only slightly lower than that of the apical eEPSCs. The same type of analysis for responses evoked by the stimulation of layer 2/3, 4 and 5 showed that layer 3 pyramidal neurons received more synaptic inputs on their basal than apical dendrites from any of layer 2/3, 4 and 5. The innervations of both apical and basal dendrites were preferentially found for source neurons located near the target neuron. The strength of synaptic inputs to layer 3 pyramidal neurons was different depending on the laminar location of presynaptic neurons and the synaptic site of the dendrites. These results suggest that synaptic inputs from different kinds of adjacent cortical neurons are integrated differently.<br/>","subitem_description_type":"Other"}]},"item_1_description_7":{"attribute_name":"学位記番号","attribute_value_mlt":[{"subitem_description":"総研大甲第1441号","subitem_description_type":"Other"}]},"item_1_select_14":{"attribute_name":"所蔵","attribute_value_mlt":[{"subitem_select_item":"有"}]},"item_1_select_8":{"attribute_name":"研究科","attribute_value_mlt":[{"subitem_select_item":"生命科学研究科"}]},"item_1_select_9":{"attribute_name":"専攻","attribute_value_mlt":[{"subitem_select_item":"20 生理科学専攻"}]},"item_1_text_10":{"attribute_name":"学位授与年度","attribute_value_mlt":[{"subitem_text_value":"2010"}]},"item_creator":{"attribute_name":"著者","attribute_type":"creator","attribute_value_mlt":[{"creatorNames":[{"creatorName":"NAKAGAWA, Nao","creatorNameLang":"en"}],"nameIdentifiers":[{}]}]},"item_files":{"attribute_name":"ファイル情報","attribute_type":"file","attribute_value_mlt":[{"accessrole":"open_date","date":[{"dateType":"Available","dateValue":"2016-02-17"}],"displaytype":"simple","filename":"甲1441_要旨.pdf","filesize":[{"value":"353.0 kB"}],"format":"application/pdf","licensetype":"license_11","mimetype":"application/pdf","url":{"label":"要旨・審査要旨","url":"https://ir.soken.ac.jp/record/2513/files/甲1441_要旨.pdf"},"version_id":"3753567e-033c-498f-a7c2-996f5b346217"}]},"item_language":{"attribute_name":"言語","attribute_value_mlt":[{"subitem_language":"eng"}]},"item_resource_type":{"attribute_name":"資源タイプ","attribute_value_mlt":[{"resourcetype":"thesis","resourceuri":"http://purl.org/coar/resource_type/c_46ec"}]},"item_title":"Dendritic domain-selectivity of intracortical excitatory inputs onto layer 2/3 pyramidal neurons","item_titles":{"attribute_name":"タイトル","attribute_value_mlt":[{"subitem_title":"Dendritic domain-selectivity of intracortical excitatory inputs onto layer 2/3 pyramidal neurons"},{"subitem_title":"Dendritic domain-selectivity of intracortical excitatory inputs onto layer 2/3 pyramidal neurons","subitem_title_language":"en"}]},"item_type_id":"1","owner":"21","path":["22"],"pubdate":{"attribute_name":"公開日","attribute_value":"2012-01-16"},"publish_date":"2012-01-16","publish_status":"0","recid":"2513","relation_version_is_last":true,"title":["Dendritic domain-selectivity of intracortical excitatory inputs onto layer 2/3 pyramidal neurons"],"weko_creator_id":"21","weko_shared_id":-1},"updated":"2023-06-20T15:50:30.814947+00:00"}