Examination of the hippocampal contribution to serotonin 5-HT2A receptor-mediated facilitation of object memory in C57BL/6J mice.
The rodent hippocampus supports non-spatial object memory. Serotonin 5-HT2A receptors (5-HT2AR) are widely expressed throughout the hippocampus. We previously demonstrated that the activation of 5-HT2ARs enhanced the strength of object memory assessed 24 h after a limited (i.e., weak memory) training procedure. Here, we examined the subcellular distribution of 5-HT2ARs in the hippocampal CA1 region and underlying mechanisms of 5-HT2AR-mediated object memory consolidation. Analyses with immuno-electron microscopy revealed the presence of 5-HT2ARs on the dendritic spines and shafts of hippocampal CA1 neurons, and presynaptic terminals in the CA1 region. In an object recognition memory procedure that places higher demand on the hippocampus, only post-training systemic or intrahippocampal administration of the 5-HT2AR agonist TCB-2 enhanced object memory. Object memory enhancement by TCB-2 was blocked by the 5-HT2AR antagonist, MDL 11,937. The memory-enhancing dose of systemic TCB-2 increased extracellular glutamate levels in hippocampal dialysate samples, and increased the mean in vivo firing rate of hippocampal CA1 neurons. In summary, these data indicate a pre- and post-synaptic distribution of 5-HT2ARs, and activation of 5-HT2ARs selectively enhanced the consolidation of object memory, without affecting encoding or retrieval. The 5-HT2AR-mediated facilitation of hippocampal memory may be associated with an increase in hippocampal neuronal firing and glutamate efflux during a post-training time window in which recently encoded memories undergo consolidation.
College of Basic Medical Sciences, Anhui Medical University, 81 Meishan Road, Hefei, Anhui 230032, China; Department of Psychology and Life Science Initiative, Charles E. Schmidt College of Science, Florida Atlantic University, 5353 Parkside Drive, Jupiter, FL 33458, USA. Electronic address: gzhang@fau.edu.
Gongliang
G
Zhang
Department of Psychology and Life Science Initiative, Charles E. Schmidt College of Science, Florida Atlantic University, 5353 Parkside Drive, Jupiter, FL 33458, USA.
David
D
Cinalli
Department of Psychology and Life Science Initiative, Charles E. Schmidt College of Science, Florida Atlantic University, 5353 Parkside Drive, Jupiter, FL 33458, USA.
Sarah J
SJ
Cohen
Department of Psychology and Life Science Initiative, Charles E. Schmidt College of Science, Florida Atlantic University, 5353 Parkside Drive, Jupiter, FL 33458, USA.
Kristina D
KD
Knapp
Department of Psychology and Life Science Initiative, Charles E. Schmidt College of Science, Florida Atlantic University, 5353 Parkside Drive, Jupiter, FL 33458, USA.
Lisa M
LM
Rios
Instituto de Investigación en Discapacidades Neurológicas (IDINE), Dept. Ciencias Medicas, Facultad de Medicina, Universidad de Castilla-La Mancha, Campus Biosanitario, Albacete, Spain.
José
J
Martínez-Hernández
Instituto de Investigación en Discapacidades Neurológicas (IDINE), Dept. Ciencias Medicas, Facultad de Medicina, Universidad de Castilla-La Mancha, Campus Biosanitario, Albacete, Spain.
Rafael
R
Luján
Department of Psychology and Life Science Initiative, Charles E. Schmidt College of Science, Florida Atlantic University, 5353 Parkside Drive, Jupiter, FL 33458, USA. Electronic address: rstackma@fau.edu.
Robert W
RW
Stackman
D000818:Animals; D004305:Dose-Response Relationship, Drug; D006624:Hippocampus / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D008568:Memory / Q000187:drug effects / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D044402:Receptor, Serotonin, 5-HT2A / Q000378:metabolism*; D021641:Recognition, Psychology / Q000187:drug effects / Q000502:physiology*; D058830:Serotonin 5-HT2 Receptor Antagonists / Q000494:pharmacology
D044402:Receptor, Serotonin, 5-HT2A; D058830:Serotonin 5-HT2 Receptor Antagonists
Glutamate; Microdialysis; Object memory; Serotonin 2A receptor; Single-unit recording