Field potential recording from rat hippocampus provides a functional evaluation method for assessing demyelination and myelin repair Mahdieh Azin, Mahdi Goudarzvand, Javad Mirnajafi-Zadeh, Mohammad Javan Department of Physiology, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran Objectives: In multiple sclerosis (MS) demyelination occurs in both white and gray matter. Here we introduce an electrophysiological approach for studying functional demyelination and myelin repair in rat hippocampus, a gray matter structure, which is frequently affected in patients suffering from MS. Methods: Using a stereotaxic approach, bipolar stimulating and monopolar recording electrodes were respectively implanted into the perforant path and the dentate gyrus of the hippocampus of the adult male Sprague-Dawley rats weighing 280–320 g. Animals received intra-hippocampal injections of saline or lysolecithin (LPC) and afterward, changes in the parameters of field potentials recorded from the dentate gyrus granular cells in response to electrical stimulation of perforant path were investigated on days 7, 14, and 28, post-lesion. Changes in the electrophysiological parameters were compared with changes in the molecular markers of myelination (myelin basic protein, MBP) and repairing cells (Olig2). Results: On day 2, a significant decrease in the slope of the population excitatory postsynaptic potential (pEPSP) and the amplitude of population spike (PS) was observed. However, during days 7–28, these parameters were increased toward control. Decreased expression of MBP and increased expression of Olig2 were observed on days 2 and 7 while the expression levels were partially reversed toward control on day 28. Discussion: Our data showed the efficacy of field potential recording for studying demyelination and endogenous myelin repair in hippocampus. Changes in electrophysiological parameters were concomitant with the level of molecular markers. This recording method provides an opportunity for functional evaluation of myelin loss and repair and the effect of potential therapies. Keywords: Demyelination, Myelin repair, Hippocampus, Endogenous progenitor and stem cells, Field potential recording, Rat Introduction Cognitive impairment and some neurological dys- functions in multiple sclerosis (MS) patients seems to be due to cerebral cortex and hippocampal insults. 1,2 Demyelination is the common pathological hallmark of MS, which is usually followed by the replacement of damaged myelin in internodes and the restoration of saltatory action potential conduction, 3 although the newly formed myelin sheath is shorter and thinner than the one before demyelination, 4 As the disease progresses, the number of lesions with persistent demyelination increases, which contributes to clinical deterioration. 5 Within the central nervous system (CNS), the endogenous neural stem cells (NSCs) renew themselves and differentiate into new neurons or glial cells following a lesion. 6 Neural stem cells are located in special zones of the adult mammalian CNS, 7,8 includ- ing the subventricular zone (SVZ) of the lateral and third ventricle, dentate gyrus, cortex, the fourth ventricle, and the central canal of the spinal cord. 8–11 When stimulated by environmental signals, NSCs proliferate and migrate to the injured regions and differentiate into oligodendrocytes, neurons, or astro- cytes according to the required phenotype, which the lesion niche dictates. 8,12 The topographical organiza- tion of these cells suggests that neurogenesis and migration are integrated in SVZ. 13 In MS patients, the presence of pre-myelinating oligodendrocytes within the lesions is well documented. 14 While tissue staining and molecular approaches are commonly used for studying the myelin repair following white matter insults, electrophysiological Correspondence to: Mohammad Javan, Department of Physiology, Faculty of Medical Sciences, Tarbiat Modares University, Islamic Republic of Iran. Email: mjavan@modares.ac.ir ß W. S. Maney & Son Ltd 2013 DOI 10.1179/1743132813Y.0000000221 Neurological Research 2013 VOL. 35 NO.8 837