In Vivo Electrophysiological Recordings

Protocols that use the in vivo preparation focus on the living, intact, anesthetized animal as the subject of the study. Recording the activity of neurons in the intact animal has numerous advantages over studies of isolated tissues. For example, the health of the tissue or neuron under study is more easily maintained and monitored. Furthermore, the neuron can be examined in its normal ionic and cellular microenvironment, with its normal complement of afferent connections intact. In addition, neurons recorded in vivo are more likely to be spontaneously active, facilitating the use of extracellular recordings and investigations into the actions of inhibitory neurotransmitters.

With respect to psychopharmacological research, the in vivo preparation provides the most direct link between neurophysiology and behavior. A drug that elicits a characteristic behavioral response can be administered systemically to examine how the drug affects neurons that are likely to participate in the behavioral response. For similar reasons, this preparation is also the most effective for investigating the mode of action of psychoactive drugs on specific neuronal systems. Although the precise locus of action through which the systemically administered drugs achieve these effects may be difficult to determine directly, whether a given drug ultimately influences the activity of a neuronal system of interest can be determined.

Experimental parameters present difficulties that, although not insurmountable, add complexity to the experimental paradigm. For example, the researcher cannot visually identify the nucleus or the cell to be recorded and must often rely on indirect techniques for cell identification. However, methods are available to enhance the ability to identify cell types. Thus, unlike the in vitro preparations, cells may be identified with respect to the projection sites of their axons by employing antidromic activation—that is, stimulation of the axon terminal region to evoke an action potential that is conducted back down the axon and subsequently recorded at the soma. Furthermore, by using in vivo intracellular recording, the neuron in question may be stained with dye and its location, morphology, and neurotransmitter content identified post hoc by various histochemical and immunocytochemical techniques (e.g., Grace and Bunney 1983; Onn et al. 1994). In addition, although the precise locus of action of systemically administered drugs cannot be determined, the drug effects obtained can be compared with those produced by directly applying the drug to the neuron through microiontophoresis (Figure 5-7) (Bloom 1974). With microiontophoresis, the drug is applied locally to the recording site, affecting the soma and proximal dendrites of the neuron recorded. However, this may be a shortcoming when the afferents to be examined synapse distally on the dendritic tree of the neuron.

FIGURE 5-7. Determining the effects of systemic and direct drug administration on neuronal activity.

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