Synchronization by Distal Dendrite-targeting Interneurons

Synchronization among neurons arises from the cooperative interaction of various cell types through excitation and inhibition. The mechanisms behind this type of neuronal orchestration are as versatile as almost no other coordination task in the brain, making its comprehension heavily challenging...

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Autor principal: Hilscher, Markus Michael
Outros Autores: Leão, Emelie Katarina Svahn
Formato: doctoralThesis
Idioma:por
Publicado em: Brasil
Assuntos:
Sincronização
Hipocampo
Células OLM
Cortex
Células Martinotti
CNPQ::OUTROS::CIENCIAS: NEUROCIÊNCIAS
Endereço do item:https://repositorio.ufrn.br/jspui/handle/123456789/24680
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id ri-123456789-24680
record_format dspace
institution Repositório Institucional
collection RI - UFRN
language por
topic Sincronização
Hipocampo
Células OLM
Cortex
Células Martinotti
CNPQ::OUTROS::CIENCIAS: NEUROCIÊNCIAS
spellingShingle Sincronização
Hipocampo
Células OLM
Cortex
Células Martinotti
CNPQ::OUTROS::CIENCIAS: NEUROCIÊNCIAS
Hilscher, Markus Michael
Synchronization by Distal Dendrite-targeting Interneurons
description Synchronization among neurons arises from the cooperative interaction of various cell types through excitation and inhibition. The mechanisms behind this type of neuronal orchestration are as versatile as almost no other coordination task in the brain, making its comprehension heavily challenging. Among many others, the high number of involved cell types, the diversity of synaptic processes as well as the contribution of a multitude of ion channels and currents span the plurality of neuronal synchronization mechanisms in our brains. Focusing on two brain areas, the hippocampus and the neocortex, this thesis aims to understand the role of distal dendritetargeting interneurons in shaping pyramidal cell activity and the timing of their action potentials. The distribution of ion channels and synaptic receptors in pyramidal cell dendrites is extremely anisotropic. Thus, interneurons innervating the proximal or distal areas of the dendrites cause different effects in the target cell when activated. For example, the distal portions of the pyramidal cell dendrites contain one of the most prominent pacemaker channels: the hyperpolarizationactivated cyclic nucleotide-gated channels. These channels produce a cationic depolarizing current (Ih) and play an essential role in the regulation of neuronal excitability. Using computational modeling, this thesis shows how the amount of Ih in certain cell types determines their spike rate, synchrony as well as power and frequency of ongoing network oscillations. Moreover, since Ih differs between brain regions as well as cell types and location, this thesis electrophysiologically explores how Ih differs along the dorsoventral axis of hippocampus in oriens-lacunosum moleculare (OLM) cells, the main distal dendrite-targeting interneurons of that region. Utilizing the main distal dendrite-targeting interneuron of the neocortex, the Martinotti cell, this thesis also shows how a defined population of interneurons can be manipulated in order to control and align pyramidal cell firing. By providing the right amount and frequency of inhibition, Martinotti cells are able to synchronize trains of subtype-specific pyramidal cells. Using optogenetic approaches to activate/inactivate populations of Martinotti cells, these dendrite-targeting interneurons are shown to trigger rebound action potentials in pyramidal cells when temporally aligned. The rebound action potentials in turn are the result of strong inhibition by Martinotti cells, giving these distal dendrite-targeting interneurons the power to reset pyramidal cell firing. Overall, Martinotti cells and OLM cells show quite striking similarities in morphological, neurochemical and electrophysiological properties. Especially, their long axonal projections to upper layers as well as their low-threshold, slow spiking fashion and the accommodating firing make these distal dendrite-targeting interneurons so special for neuronal synchronization.
author2 Leão, Emelie Katarina Svahn
author_facet Leão, Emelie Katarina Svahn
Hilscher, Markus Michael
format doctoralThesis
author Hilscher, Markus Michael
author_sort Hilscher, Markus Michael
title Synchronization by Distal Dendrite-targeting Interneurons
title_short Synchronization by Distal Dendrite-targeting Interneurons
title_full Synchronization by Distal Dendrite-targeting Interneurons
title_fullStr Synchronization by Distal Dendrite-targeting Interneurons
title_full_unstemmed Synchronization by Distal Dendrite-targeting Interneurons
title_sort synchronization by distal dendrite-targeting interneurons
publisher Brasil
publishDate 2018
url https://repositorio.ufrn.br/jspui/handle/123456789/24680
work_keys_str_mv AT hilschermarkusmichael synchronizationbydistaldendritetargetinginterneurons
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spelling ri-123456789-246802022-06-10T18:53:28Z Synchronization by Distal Dendrite-targeting Interneurons Hilscher, Markus Michael Leão, Emelie Katarina Svahn https://orcid.org/0000-0001-7295-1233 http://lattes.cnpq.br/1279823352935722 Leão, Richardson Naves http://lattes.cnpq.br/0683942077872227 Kushmerick, Christopher http://lattes.cnpq.br/6998917765406696 Silberberg, Gilad Schmidt, Kerstin Erika Cammarota, Martin Pablo https://orcid.org/0000-0001-9741-5074 http://lattes.cnpq.br/4888317387600937 Sincronização Hipocampo Células OLM Cortex Células Martinotti CNPQ::OUTROS::CIENCIAS: NEUROCIÊNCIAS Synchronization among neurons arises from the cooperative interaction of various cell types through excitation and inhibition. The mechanisms behind this type of neuronal orchestration are as versatile as almost no other coordination task in the brain, making its comprehension heavily challenging. Among many others, the high number of involved cell types, the diversity of synaptic processes as well as the contribution of a multitude of ion channels and currents span the plurality of neuronal synchronization mechanisms in our brains. Focusing on two brain areas, the hippocampus and the neocortex, this thesis aims to understand the role of distal dendritetargeting interneurons in shaping pyramidal cell activity and the timing of their action potentials. The distribution of ion channels and synaptic receptors in pyramidal cell dendrites is extremely anisotropic. Thus, interneurons innervating the proximal or distal areas of the dendrites cause different effects in the target cell when activated. For example, the distal portions of the pyramidal cell dendrites contain one of the most prominent pacemaker channels: the hyperpolarizationactivated cyclic nucleotide-gated channels. These channels produce a cationic depolarizing current (Ih) and play an essential role in the regulation of neuronal excitability. Using computational modeling, this thesis shows how the amount of Ih in certain cell types determines their spike rate, synchrony as well as power and frequency of ongoing network oscillations. Moreover, since Ih differs between brain regions as well as cell types and location, this thesis electrophysiologically explores how Ih differs along the dorsoventral axis of hippocampus in oriens-lacunosum moleculare (OLM) cells, the main distal dendrite-targeting interneurons of that region. Utilizing the main distal dendrite-targeting interneuron of the neocortex, the Martinotti cell, this thesis also shows how a defined population of interneurons can be manipulated in order to control and align pyramidal cell firing. By providing the right amount and frequency of inhibition, Martinotti cells are able to synchronize trains of subtype-specific pyramidal cells. Using optogenetic approaches to activate/inactivate populations of Martinotti cells, these dendrite-targeting interneurons are shown to trigger rebound action potentials in pyramidal cells when temporally aligned. The rebound action potentials in turn are the result of strong inhibition by Martinotti cells, giving these distal dendrite-targeting interneurons the power to reset pyramidal cell firing. Overall, Martinotti cells and OLM cells show quite striking similarities in morphological, neurochemical and electrophysiological properties. Especially, their long axonal projections to upper layers as well as their low-threshold, slow spiking fashion and the accommodating firing make these distal dendrite-targeting interneurons so special for neuronal synchronization. A sincronização neuronal surge de uma interação cooperativa de vários tipos celulares através de excitação e inibição. Os mecanismos por trás desse tipo de coordenação neuronal são, provavelmente, os mais dinâmicos entre as funções cerebrais, dificultando sua compreensão. Entre os fatores que dificultam o estudo da sincronia, pode-se citar: o vasto número de tipos de celulares, a diversidade de processos sinápticos, a contribuição de uma multiplicidade de canais e correntes iônicas, entre outros. Essa tese tem como objetivo entender o papel de interneurônios que especificamente inervam o domínio distal dos dendritos de células piramidais do hipocampo e neocórtex, na sincronização de neurônios em suas respectivas redes. A distribuição de canais iônicos e receptors sinápticos em dendritos de células piramidais é extremamente anisotrópica. Assim, interneurônios que inervam domínios proximais e distais dos dendritos causam efeitos distintos na célula alvo quando ativados. Por exemplo, porções distais dos dendritos contém em abundância um dos principais canais marcapassos em neurônios: o canal regulado por nucleotídeo cíclico ativado por hiperpolarização. Esses canais produzem uma corrente catiônica despolarizante (Ih) e tem um papel importante na regulação da excitabilidade neuronal alterando dramaticamente as propriedades de disparo de neurônios. Usando modelagem computacional, essa tese mostra como a amplitude de Ih em certos tipos celulares muda a taxa de disparo de um neurônio, sua sincronia além da energia espectral e frequência de oscilações. Além disso, como a expressão de Ih difere entre regiões cerebrais, localização e tipos celulares, essa tese, fazendo o uso de patch clamp, explora como Ih difere ao longo do eixo dorsoventral do hipocampo em células oriens-lacunosum moleculare (OLM), que são os principais interneurônios que inervam dendritos distais dessa região. Ademais, estudou-se aqui as células Martinotti, interneurônios que inervam os dendritos distais do neocórtex. Nesse estudo, mostrou-se como uma população definida de interneurônios pode ser manipulada com o objetivo de controlar e coordenar o disparo de células piramidais. Ao fornecer inibição com energia e frequência adequada, as células Martinotti afetam especificamente um único tipo de célula piramidal. Usando optogenética para ativar/desativar populações de células Martinotti, é possível gerar potenciais de ação rebote em células piramidais quando alinhadas temporalmente. Os potenciais de ação rebote, por sua vez, são resultado de uma forte inibição produzida pelas células Martinotti, o que faz com que esses esses interneurônios possam resetar o disparo de células piramidais. De forma geral, células Martinotti e células OLM mostram similaridades surpreendentes em propriedades morfológicas, neuroquímicas e eletrofisiológicas. Especialmente, suas longas projeções axonais para camadas superiores assim como seus modos de disparo lentos, com baixos limiares e acomodativos tornam esses neurônios singulares em suas capacidades de sincronizar os circuitos nos quais estão inseridos. 2018-01-29T12:29:16Z 2018-01-29T12:29:16Z 2016-12-01 doctoralThesis HILSCHER, Markus Michael. Synchronization by Distal Dendrite-targeting Interneurons. 2016. 151f. Tese (Doutorado em Neurociências) - Universidade Federal do Rio Grande do Norte, Universidade Federal do Rio Grande do Norte, Natal, 2016. https://repositorio.ufrn.br/jspui/handle/123456789/24680 por Acesso Aberto application/pdf Brasil UFRN PROGRAMA DE PÓS-GRADUAÇÃO EM NEUROCIÊNCIAS

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