Not Itself Histamine, but H3R Antagonists/Inverse Agonist Thioperamide Enhances Long-term Potentiation in the Dentate Gyrus of Urethane- Anesthetized Rats

Cem Suer,Seda Arta Ay

doi:10.21767/2171-6625.1000270

Abstract

Purpose: Although the histamine receptor antagonists have been reported to enhance consolidation of memory in diverse disease states of the central nervous system, their contribution to the long-term potentiation (LTP), a cellular form of learning and memory, remains unknown. Herein, we evaluate the effect of H3 receptor (H3R) antagonist thioperamide (inverse agonist) on the LTP in healthy rats and compare the effect with that of histamine as an agonist, and pyrilamine, as a H2R antagonist. Methods: LTP was induced in the dentate gyrus, where field potentials were recorded during infusions of saline, histamine, thioperamide or pyrilamine alone by application of high- frequency stimulation protocols. Results: The short-term and long-temp potentiation of EPSP, not of PS, in the thioperamide group were significantly higher in comparison with controls, indicating that induction and maintenance of synaptic, not somatic, LTP further enhanced by H3R antagonism. There were also significant differences in short-term and long-term potentiation of PS between the histamine and pyrilamine groups, indicating H1R-mediated dyssynchrony in granule cell of the dentate gyrus. Conclusion: Histamine seems not to play a significant functional role in the perforant pathway- dentate gyrus synapses, but the antagonism of H3R should be considered in treatment of cognitive dysfunctions, although other forms of synaptic plasticity such as longterm depression and depotentiation of LTP are needed.

Highlights

Several lines of evidence indicate that the DG encodes the contextual memory engrams that represent discrete environments [1,2,3]
Pyrilamine or thioperamide has no effect on baseline transmission in the synapses between perforant pathway and the dentate gyrus
The input/output curve represents a global relationship between stimulus intensity and the synaptic (EPSP slope) and spike (PS amplitude) components of the compound field potential, namely the baseline synaptic transmission

Summary

Introduction

Several lines of evidence indicate that the DG encodes the contextual memory engrams that represent discrete environments [1,2,3]. The granule cells in the dentate gyrus region of the hippocampus are able to induce long-term potentiation (LTP), which is a cellular model of learning and memory [4]. They receive their primary excitatory afferent input from the entorhinal cortex via the so-called perforant pathway [5]. In the hippocampal formation the dentate gyrus contains the highest density of H3R binding sites in rat brain [23] These receptors are presynaptically located, are negatively coupled to adenylyl cyclase and mediate presynaptic inhibition of neuronal histamine release [24] as well as other neurotransmitters [25]. The action of thioperamide was completely different from both histamine and pyrilamine, suggesting post-synaptic H3R involvement in the dentate gyrus LTP

Materials and Methods

Results

Discussion