Viral Vectors to Study Synaptic Function - Viral Vector Approaches in Neurobiology and Brain Diseases - page 109

Chapter 6

Viral Vectors to Study Synaptic Function

Hélène Marie

Abstract

Neurons display strong plasticity of their cellular properties, especially by modulation of their synaptic
inputs. The development of viral vectors as biological tools has been extremely useful to molecularly
manipulate protein expression in the rodent brain for a better understanding of the molecular mechanisms
governing such synaptic plasticity. The use of viruses has several advantages. First, it allows for expression
of a protein of interest in a temporally and spatially restricted manner. Second, it allows for a direct com-
parison of cellular properties between neurons expressing the protein of interest and neighboring control
neurons from the same animal. Finally, when these viral vectors are used in vivo, the neurons expressing
the virally encoded recombinant proteins are allowed to do so while remaining in their physiological envi-
ronment in freely behaving animals. In this chapter, we describe how these viral vectors can be used to
study synaptic function. As an example, we focus on the use of sindbis viruses to express mutant proteins
in the rat hippocampus in vivo for investigation of their role in synaptic function.

Key words Viral vectors, Sindbis virus, Synaptic plasticity, Hippocampus, Electrophysiology, CREB

1 Introduction

The hippocampus is composed of a trisynaptic pathway consisting
of the three main types of excitatory cells: the granule cells of the
dentate gyrus connecting to CA3 pyramidal neurons connecting to
CA1 pyramidal neurons. The synaptic plasticity of these neurons is
a central process driving hippocampus-dependent memory encod-
ing. The molecular mechanisms underlying hippocampal synaptic
activity and plasticity are quite complex but relatively well defi ned
in the CA1 pyramidal neurons [ 1 ]. Two main types of plasticities
have been described in these neurons: a Hebbian plasticity and a
homeostatic plasticity. Excitatory synapses on these cells contain
2-amino-3-(5-methyl-3-oxo-1,2-oxazol-4-yl)propanoic acid
(AMPA) and N -Methyl-d-aspartic acid (NMDA) ionotropic gluta-
mate receptors (AMPAR and NMDAR, respectively) within the
postsynaptic density (PSD) located in dendritic spines. Basal synap-
tic transmission is largely mediated by AMPARs. Brief periods of