title: Chronic Fluoxetine Induces the Enlargement of Perforant Path-Granule Cell Synapses in the Mouse Dentate Gyrus.
abstract: A selective serotonin reuptake inhibitor is the most commonly prescribed antidepressant for the treatment of major depression. However, the mechanisms underlying the actions of selective serotonin reuptake inhibitors are not fully understood. In the dentate gyrus, chronic fluoxetine treatment induces increased excitability of mature granule cells (GCs) as well as neurogenesis. The major input to the dentate gyrus is the perforant path axons (boutons) from the entorhinal cortex (layer II). Through voltage-sensitive dye imaging, we found that the excitatory neurotransmission of the perforant path synapse onto the GCs in the middle molecular layer of the mouse dentate gyrus (perforant path-GC synapse) is enhanced after chronic fluoxetine treatment (15 mg/kg/day, 14 days). Therefore, we further examined whether chronic fluoxetine treatment affects the morphology of the perforant path-GC synapse, using FIB/SEM (focused ion beam/scanning electron microscopy). A three-dimensional reconstruction of dendritic spines revealed the appearance of extremely large-sized spines after chronic fluoxetine treatment. The large-sized spines had a postsynaptic density with a large volume. However, chronic fluoxetine treatment did not affect spine density. The presynaptic boutons that were in contact with the large-sized spines were large in volume, and the volumes of the mitochondria and synaptic vesicles inside the boutons were correlated with the size of the boutons. Thus, the large-sized perforant path-GC synapse induced by chronic fluoxetine treatment contains synaptic components that correlate with the synapse size and that may be involved in enhanced glutamatergic neurotransmission.
authors.affiliation: Department of Pharmacology, Kurume University School of Medicine, 67 Asahi-machi, Kurume, Fukuoka, 830-0011, Japan.
authors.forename: Yosuke
authors.initials: Y
authors.lastname: Kitahara
authors.affiliation: Department of Anatomy, Kurume University School of Medicine, 67 Asahi-machi, Kurume, Fukuoka, 830-0011, Japan.
authors.forename: Keisuke
authors.initials: K
authors.lastname: Ohta
authors.affiliation: Department of Physiology, Kurume University School of Medicine, 67 Asahi-machi, Kurume, Fukuoka, 830-0011, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Hasuo
authors.affiliation: Department of Pharmacology, Kurume University School of Medicine, 67 Asahi-machi, Kurume, Fukuoka, 830-0011, Japan.
authors.forename: Takahide
authors.initials: T
authors.lastname: Shuto
authors.affiliation: Department of Pharmacology, Kurume University School of Medicine, 67 Asahi-machi, Kurume, Fukuoka, 830-0011, Japan.
authors.forename: Mahomi
authors.initials: M
authors.lastname: Kuroiwa
authors.affiliation: Department of Pharmacology, Kurume University School of Medicine, 67 Asahi-machi, Kurume, Fukuoka, 830-0011, Japan.
authors.forename: Naoki
authors.initials: N
authors.lastname: Sotogaku
authors.affiliation: Department of Anatomy, Kurume University School of Medicine, 67 Asahi-machi, Kurume, Fukuoka, 830-0011, Japan.
authors.forename: Akinobu
authors.initials: A
authors.lastname: Togo
authors.affiliation: Department of Anatomy, Kurume University School of Medicine, 67 Asahi-machi, Kurume, Fukuoka, 830-0011, Japan.
authors.forename: Kei-ichiro
authors.initials: K
authors.lastname: Nakamura
authors.affiliation: Department of Pharmacology, Kurume University School of Medicine, 67 Asahi-machi, Kurume, Fukuoka, 830-0011, Japan.
authors.forename: Akinori
authors.initials: A
authors.lastname: Nishi
mesh_terms: D000818:Animals; D018891:Dentate Gyrus / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D004594:Electrophysiology; D005473:Fluoxetine / Q000494:pharmacology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009474:Neurons / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D019580:Perforant Pathway / Q000187:drug effects*; D013569:Synapses / Q000187:drug effects / Q000502:physiology*; D009435:Synaptic Transmission / Q000187:drug effects*
chemical_list: D005473:Fluoxetine