IJPPP Copyright © 2009-All rights reserved. Published by e-Century Publishing Corporation, Madison, WI 53711
Int J Physiol Pathophysiol Pharmacol 2012;4(4):201-210

Review Article
Serotonergic modulation of Neural activities in the
entorhinal cortex

Saobo Lei

Department of Pharmacology, Physiology and Therapeutics, School of Medicine and Health Sciences, University
of North Dakota, Grand Forks, ND 58203, USA

Received November 27, 2012; Accepted December 19, 2012; Epub December 26, 2012; Published December
31, 2012

Abstract: The entorhinal cortex (EC) is considered as the gate to control the flow of information into and out of the
hippocampus. The EC is important for numerous physiological functions such as emotional control, learning and
memory and pathological disorders including Alzheimer’s disease, schizophrenia and temporal lobe epilepsy. Serotonin
is a classical neurotransmitter which may modify these physiological functions and pathology of neurological
diseases. The EC receives profuse serotonergic innervations from the raphe nuclei in the brainstem and expresses
high density of serotonergic receptors including 5-HT1A, 5-HT1D, 5-HT1E, 5-HT2A, 5-HT3 and 5-HT6. The prominent innervation
by serotonergic neurons and the dense expression of serotonergic receptors in the EC suggest that serotonin
is a major modulator in this brain region. Serotonin exerts inhibitory effects in the EC. Serotonin hyperpolarizes
entorhinal neurons and inhibits the excitatory synaptic transmission via activation of 5-HT1A receptors but facilitates
GABA release via activation of 5-HT2A receptors. Both 5-HT1A and 5-HT2A receptors are required for serotonin-induced
inhibition of epileptiform activity although 5-HT3 receptors may be involved in serotonin-mediated inhibition of acetylcholine
release in the EC. Furthermore, the functions of serotonin in the EC may be implicated in Parkinson’s
disease, Alzheimer’s disease and depression. Thus, understanding the roles of serotonergic modulation in the EC
is of major clinical importance. Here, I review recent findings concerning the effects of serotonin on neural circuitry
activity in the EC. (IJPPP1211003).

Keywords: Glutamate, GABA, synaptic transmission, epilepsy, neurotransmitter, G-protein coupled receptor

Address all correspondence to:
Dr. Saobo Lei
Department of Pharmacology, Physiology and Therapeutics
School of Medicine and Health Sciences, University of North Dakota
Grand Forks, ND 58203, USA.
Phone: 701-7774745; Fax: 701-7774490
E-mail: saobo.lei@med.und.edu