UNIT 6.13 Synaptic Plasticity in the Hippocampal Slice Preparation Zuner A. Bortolotto, 1 Mascia Amici, 1 William W. Anderson, 1 John T.R. Isaac, 2 and Graham L. Collingridge 1,3 1 MRC Centre for Synaptic Plasticity, School of Physiology and Pharmacology, University of Bristol, Bristol, United Kingdom 2 Eli Lilly & Co., Lilly Research Centre, Windlesham, Surrey, United Kingdom 3 Department of Brain and Cognitive Sciences, Seoul National University, Seoul, Korea ABSTRACT Synaptic plasticity is the process by which the brain alters the strength of its synaptic connections, a fundamental function of the brain that enables individuals to learn from experience. The study of synaptic plasticity often involves the application of standard in vitro electrophysiological techniques to hippocampal slice preparations. This unit discusses many of the special considerations that are applicable for the optimal study of synaptic plasticity in this system. Most of these principles also apply to the study of synaptic plasticity in other brain slice preparations. Curr. Protoc. Neurosci. 54:6.13.1- 6.13.26. C  2011 by John Wiley & Sons, Inc. Keywords: LTP  LTD  hippocampus  synaptic plasticity  glutamate receptors  organotypic slice  WinLTP INTRODUCTION The way that individuals learn from experience is by alterations in the efficiency of com- munication at their synapses in the brain. Thus, the strength of synapses (how effectively they relay information) is not fixed but can be modified by activity. This modifiability means that the brain is plastic (i.e., programmable). Indeed, the plasticity mediated by changes at synapses (i.e., synaptic plasticity) is the principal means by which the nervous system adapts to an organism’s external environment. Not surprisingly, therefore, the study of synaptic plasticity represents a major thrust of contemporary neuroscience. Synaptic plasticity is crucial to the development of the nervous system and thereafter to the ability of an individual to learn and remember new information and to adjust its behavior accordingly. Synaptic plasticity is also believed to be important in neurological disorders, such as epilepsy and neurodegeneration, and in recovery from neuronal injury. Synaptic plasticity is usually studied using electrophysiological techniques (UNITS 6.1 & 6.10). The hippocampal slice is the principal preparation for studying synaptic plasticity. This is due to its orderly anatomical arrangement, which facilitates experimentation, and because several pathways within the hippocampus display remarkably pronounced plas- ticity. The methods used to prepare and record electrical activity from the hippocampal slice preparation are presented in UNIT 6.4. The purpose of this unit is to highlight the special considerations required to effectively study synaptic plasticity in the hippocampal slice. These considerations also apply to other preparations, such as slice preparations from neocortex and cerebellum. The Basic Protocol describes a method for using extra- cellular recording techniques to study long-term potentiation (LTP) in the hippocampal slice. Current Protocols in Neuroscience 6.13.1-6.13.26, January 2011 Published online January 2011 in Wiley Online Library (wileyonlinelibrary.com). DOI: 10.1002/0471142301.ns0613s54 Copyright C  2011 John Wiley & Sons, Inc. Phenotypic Analysis 6.13.1 Supplement 54