Effects of Gastrin-releasing Peptide on Hippocampal Neural Networks in Vascular Dementia Rats

Gastrin-releasing peptide (GRP) has been confirmed to exhibit a variety of physiological functions in the brain and play a role in many neurological diseases. Our previous research found that GRP could restore the impaired synaptic plasticity and the spatial learning and memory impairments induced by vascular dementia (VD). However, the specific mechanisms of GRP affecting hippocampus, especially the effects on the neuronal oscillations were still poorly understood. In this study, we examined the effects of GRP on the changes of the interactions between theta and gamma oscillations in the hippocampal CA3-CA1 pathway of VD rats and explored the potential electrophysiological mechanism. To this purpose, local field potentials (LFPs) simultaneously collected from hippocampal CA3 and CA1 were measured by the power spectrum, phase synchronization, phase-phase coupling (PPC) and phase-amplitude coupling (PAC). We found that GRP substantially restored the phase synchronization of the theta and gamma oscillations. The GRP also significantly improved the strength of theta-gamma cross-frequency coupling (including theta-gamma PPC and theta-gamma PAC) in the CA3-CA1 network. The results indicated that GRP could alleviate the changes of neural activities in hippocampal CA3-CA1 pathway induced by VD. This might be an electrophysiological mechanism for GRP preventing cognitive impairments induced by VD.

I. Introduction

Gastrin-releasing peptide (GRP) exhibits varieties of physiological functions by binding to the gastrin-releasing peptide receptor (GRPR, also called BB2) [1]. Some evidences in rodents suggested that dysfunctions in GRPR expression and GRP signaling might play a vital in varieties of cognitive function and central nervous system (CNS) disorders such as Parkinson's disease (PD) and Alzheimer's disease (AD) [2]-[5]. Moreover, a recent research indicated that GRP might relate to modulate neuronal and neurogenesis growth and might contribute to hippocampus function [6].