Overview of brain microdialysis

Abstract

The technique of microdialysis enables sampling and collecting of small-molecular-weight substances from the interstitial space. It is a widely used method in neuroscience and is one of the few techniques available that permits quantification of neurotransmitters, peptides, and hormones in the behaving animal. More recently, it has been used in tissue preparations for quantification of neurotransmitter release. This unit provides a brief review of the history of microdialysis and its general application in the neurosciences. The authors review the theoretical principles underlying the microdialysis process, methods available for estimating extracellular concentration from dialysis samples (i.e., relative recovery), the various factors that affect the estimate of in vivo relative recovery, and the importance of determining in vivo relative recovery to data interpretation. Several areas of special note, including impact of tissue trauma on the interpretation of microdialysis results, are discussed. Step-by-step instructions for the planning and execution of conventional and quantitative microdialysis experiments are provided.

Figure 7.1.1

Representation of the “inside view” of a microdialysis probe. The microdialysis probe, which consists of an inflow and outflow tubing (A) separated by tubing made of dialysis membrane, is implanted surgically into a specific area within the brain (B). The enlarged view (C) illustrates the complex composition of the fluid through which analytes (black dots) must diffuse to get to the microdialysis probe. The presence of impermeable cells such as blood vessels (V) reduces the fluid volume surrounding the probe and increases the diffusional path (arrow) of analytes moving toward the probe. The net effect is a decreased diffusivity in this phase.

Figure 7.1.2

No-net-flux microdialysis of DA under well-stirred conditions in vitro at 37°C and in vivo in mouse nucleus accumbens (vehicle-treated controls). (A) Plot of the average gain or loss of DA ( $C_{\text{d}}^{\text{in}}-C_{\text{d}}^{\text{out}}$) to or from perfusate and the average linear regression fit of the data: in vitro (open circles), in vivo (filled circles). The slope of the regression line represents the extraction fraction ( $E_{\text{d}}^{\text{ws}}$ in vitro, E_d in vivo). (B) Bar graph of extraction fraction values expressed as the mean ± S.E.M. (*) Denotes significant difference in between in vitro and in vivo measurements. Reproduced with permission from Chefer et al., 2006.