Аннотация
Роль серотониновых рецепторов 5-НТ5А в модуляции миниатюрной тормозной синаптической активности исследована с помощью внутриклеточной регистрации миниатюрных глицинергических тормозных постсинаптических потенциалов (глимТПСП) в мотонейронах поясничных сегментов изолированного спинного мозга лягушки Rana ridibunda. В среде, содержащей ТТх, СNQX, DAP5, bicucullinе, аппликация агониста серотониновых рецепторов 5-СТ (10 мкМ) с высокой аффинностью к 5-НТ5А приводила к подавлению частоты на 86%, а также исчезновению высокоамплитудных глимТПСП (200- 500 мкВ) при сохранении редких потенциалов амплитудой около 100 мкВ, что свидетельствует о возможности пре- и постсинаптического действия 5-СТ в такой концентрации, не исчерпывающегося его действием только на 5-НТ5А рецепторы. Добавление в среду метисергида, блокатора 5-НТ 1,2 рецепторов, снижало среднюю частоту глимТПСП на 67 %, частоту высокоамплитудных событий в 5 раз и их среднюю амплитуду на 20%, что может свидетельствовать об участии 5-НТ5А рецепторов в пре- и постсинаптической модуляции в глимТПСП мотонейронов. Аппликация 1 мкМ 5-СТ приводила к уменьшению частоты глимТПСП на 49% без заметного изменения амплитуды глимТПСП, а последующее введение в раствор SB-699551, селективного антагониста 5-НТ5А рецепторов, увеличивало частоту событий на 41% , что подтверждает участие 5-НТ5А рецепторов в пресинаптической модуляции глимТПСП. Иммунофлуоресцентное исследование показало, что супра- и интраспинальные 5-НТ+ ir нейроны дают обильные ветвления в поясничном отделе с возможностью образования аксосоматических контактов с мечеными мотонейронами и аксодендритных контактов на проксимальных и дистальных участках их дендритов. Также возможно образование контактов в перимедулярном сплетении, пронизанном дистальными дендритами мотонейронов и астроцитарными отростками. Это представляет структурную основу для пост-, пре- и экстрасинаптической модуляции активности мотонейронов серотонином. Возможность постсинаптической модуляции активности мотонейронов через 5-НТ5А рецепторы подтверждает точечноподобная флуоресценция 5-НТ5АRlike+ сигнала на дендритах и телах меченых мотонейронов, который присутствует в нейропиле, но отсутствует в перимедулярном сплетении. Двойное мечение антителами к 5-НТ5А рецептору и Са 2+ -связывающему белку, парвальбумину (PV+ir), выявило локализацию 5-НТ5АRlike+ в миелиновой оболочке волокон дорсальных и вентромедиальных канатиков. На препаратах после длительной стимуляции вентральных корешков через всасывающие электроды при мечении мотонейронов биоцитином обнаружен яркий 5-НТ5АRlike+ сигнал в миелине моторных аксонов, дорсальнокорешковых волокон, входящих в мозг в области дорсального рога и отдельных волокон вентромедиального канатика. Обсуждается участие экстрасинаптических рецепторов 5-НТ5А в функционировании цепей обратной связи активности поясничных мотонейронов, с возможным участием в этих цепях глиальных элементов.
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