Serotonin deficiency increases context-dependent fear learning through modulation of hippocampal activity
Waider J., Popp S., Mlinar B., Montalbano A., Bonfiglio F., Aboagye B., Thuy E., Kern R., Thiel C., Araragi N., Svirin E. P., Schmitt-Böhrer A. G., Corradetti R., Lowry C. A., Lesh K. Yu.
Frontiers in Neuroscience
Vol.13, IssueAPR, Num.245
Опубликовано: 2019
Тип ресурса: Статья
DOI:10.3389/fnins.2019.00245
Аннотация:
Brain serotonin (5-hydroxytryptamine, 5-HT) system dysfunction is implicated in exaggerated fear responses triggering various anxiety-, stress-, and trauma-related disorders. However, the underlying mechanisms are not well understood. Here, we investigated the impact of constitutively inactivated 5-HT synthesis on context-dependent fear learning and extinction using tryptophan hydroxylase 2 (Tph2) knockout mice. Fear conditioning and context-dependent fear memory extinction paradigms were combined with c-Fos imaging and electrophysiological recordings in the dorsal hippocampus (dHip). Tph2 mutant mice, completely devoid of 5-HT synthesis in brain, displayed accelerated fear memory formation and increased locomotor responses to foot shock. Furthermore, recall of context-dependent fear memory was increased. The behavioral responses were associated with increased c-Fos expression in the dHip and resistance to foot shock-induced impairment of hippocampal long-term potentiation (LTP). In co
Ключевые слова:
Extinction; Fear learning; Hippocampus; Immediate-early gene; Knockout; Long-term potentiation; Serotonin deficiency; Tryptophan hydroxylase 2
protein c fos; serotonin; tryptophan hydroxylase 2; adult; animal experiment; Article; controlled study; fear; footshock; hippocampus; knockout mouse; learning; locomotion; long term potentiation; male; memory; mouse; neuromodulation; nonhuman; protein expression; reinforcement
Язык текста: Английский
ISSN: 1662-453X
Waider J.
Popp S.
Mlinar B.
Montalbano A.
Bonfiglio F.
Aboagye B.
Thuy E.
Kern R.
Thiel C.
Araragi N.
Svirin E. P. Evgenij Pavlovich 1991-
Schmitt-Böhrer A. G.
Corradetti R.
Lowry C. A.
Lesh K. Yu. Klaus-Peter Yulius 1957-
Wаидер Й.
Попп С.
Млинар Б.
Монталбано А.
Бонфиглио Ф.
Абоагье Б.
Тхуy Е.
Керн Р.
Тхиел C.
Арараги Н.
Свирин Е. П. Евгений Павлович 1991-
Счмитт-Бöхрер А. Г.
Cоррадетти Р.
Лоwрy C. А.
Леш К. Ю. Клаус-Петер Юлиус 1957-
Serotonin deficiency increases context-dependent fear learning through modulation of hippocampal activity
Текст визуальный непосредственный
Frontiers in Neuroscience
Frontiers Research Foundation
Vol.13, IssueAPR Num.245
2019
Статья
Extinction Fear learning Hippocampus Immediate-early gene Knockout Long-term potentiation Serotonin deficiency Tryptophan hydroxylase 2
protein c fos serotonin tryptophan hydroxylase 2 adult animal experiment Article controlled study fear footshock hippocampus knockout mouse learning locomotion long term potentiation male memory mouse neuromodulation nonhuman protein expression reinforcement
Brain serotonin (5-hydroxytryptamine, 5-HT) system dysfunction is implicated in exaggerated fear responses triggering various anxiety-, stress-, and trauma-related disorders. However, the underlying mechanisms are not well understood. Here, we investigated the impact of constitutively inactivated 5-HT synthesis on context-dependent fear learning and extinction using tryptophan hydroxylase 2 (Tph2) knockout mice. Fear conditioning and context-dependent fear memory extinction paradigms were combined with c-Fos imaging and electrophysiological recordings in the dorsal hippocampus (dHip). Tph2 mutant mice, completely devoid of 5-HT synthesis in brain, displayed accelerated fear memory formation and increased locomotor responses to foot shock. Furthermore, recall of context-dependent fear memory was increased. The behavioral responses were associated with increased c-Fos expression in the dHip and resistance to foot shock-induced impairment of hippocampal long-term potentiation (LTP). In co