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The role of serotonin in memory: interactions with neurotransmitters and downstream signaling

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Abstract

Serotonin, or 5-hydroxytryptamine (5-HT), is found to be involved in many physiological or pathophysiological processes including cognitive function. Seven distinct receptors (5-HT1–7), each with several subpopulations, have been identified for serotonin, which are different in terms of localization and downstream signaling. Because of the development of selective agonists and antagonists for these receptors as well as transgenic animal models of cognitive disorders, our understanding of the role of serotonergic transmission in learning and memory has improved in recent years. A large body of evidence indicates the interplay between serotonergic transmission and other neurotransmitters including acetylcholine, dopamine, γ-aminobutyric acid (GABA) and glutamate, in the neurobiological control of learning and memory. In addition, there has been an alteration in the density of serotonergic receptors in aging and Alzheimer’s disease, and serotonin modulators are found to alter the process of amyloidogenesis and exert cognitive-enhancing properties. Here, we discuss the serotonin-induced modulation of various systems involved in mnesic function including cholinergic, dopaminergic, GABAergic, glutamatergic transmissions as well as amyloidogenesis and intracellular pathways.

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Abbreviations

2PSDT:

Two-platform spatial discrimination task

3xTg-AD:

Triple-transgenic mouse model of Alzheimer’s disease

5-HT:

5-Hydroxytryptamine

AC:

Adenylate cyclase

Ach:

Acetylcholine

AD:

Alzheimer’s disease

APP:

Amyloid precursor protein

ARN:

Anterior raphe nucleus

Aβ:

Amyloid β

cAMP:

Cyclic adenosine monophosphate

cGMP:

Cyclic guanosine monophosphate

CPP:

Conditioned place preference

CREB:

cAMP-response element binding

DA:

Dopamine

DH:

Dorsal hippocampus

DMTS:

Delayed matching to sample

DNPTP:

Delayed non-matching to position

DRN:

Dorsal raphe nucleus

EPAC:

Exchange proteins activated by cAMP

EPSCs:

Excitatory postsynaptic currents

ERK:

Extracellular signal-regulated kinase

FC:

Frontal cortex

GABA:

Gamma (γ)-aminobutyric acid

GAD:

Glutamic acid decarboxylase

Gi :

Inhibitory G-protein

Glu:

Glutamate

GPCRs:

G-protein-coupled receptors

Gs:

Stimulatory G-protein

GSK3:

Glycogen synthase kinase 3

i.c.v.:

Intracerebroventricular

i.p.:

Intraperitoneal

i.v.:

Intravenous

LTP:

Long-term potentiation

LTD:

Long-term depression

MAPK:

Mitogen-activated protein kinases

MBN:

Magnocellular nucleus basalis

mGluR:

Metabotropic glutamate receptor

MS/vDB:

Medial septum and the adjacent vertical limb of the diagonal band of Broca area

MWM:

Morris water maze

NAc:

Nucleus accumbens

NMDA:

N-Methyl-D-aspartate

NO:

Nitric oxide

ORT:

Object recognition task

PA:

Passive avoidance

PCA:

p-Chloroamphetamine

PDE:

Phosphodiesterase

PFC:

Prefrontal cortex

PI:

Pavlovian/instrumental autoshaping

PKA:

Protein kinase A

PKC:

Protein kinase C

PKG:

Protein kinase G

PKM:

Protein kinase M

PLA2:

Phospholipase A2

PS1:

Presenilin-1

PT:

Pass through

s.c.:

Subcutaneous

SA:

Self-administration

sIPSC:

Spontaneous inhibitory postsynaptic current

VTA:

Ventral tegmental area

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Authors and Affiliations

  1. Department of Molecular Imaging, The Persian Gulf Biomedical Sciences Research Institute, Bushehr University of Medical Sciences, Bushehr, Iran

    Mohammad Seyedabadi

  2. Department of Psychiatry and Neuroscience, Université Laval, Quebec, QC, Canada

    Gohar Fakhfouri

  3. Institut Universitaire en Santé Mentale de Québec (IUSMQ) Research Center, Quebec, QC, Canada

    Gohar Fakhfouri

  4. Department of Pharmaceutics, Faculty of Pharmacy, Shahid Sadoughi University of Medical Sciences, Yazd, Iran

    Vahid Ramezani

  5. Department of Pharmacology, School of Medicine, Tehran University of Medical Sciences, P. O. Box 13145-784, Tehran, Iran

    Shahram Ejtemaei Mehr & Reza Rahimian

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  1. Mohammad Seyedabadi
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Seyedabadi, M., Fakhfouri, G., Ramezani, V. et al. The role of serotonin in memory: interactions with neurotransmitters and downstream signaling. Exp Brain Res 232, 723–738 (2014). https://doi.org/10.1007/s00221-013-3818-4

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