The methods outlined here are directed at analyzing the activity of individual neurons as a means of assessing their role in pharmacological responses or behavioral actions. This is based on the premise that the discharge of a neuron in some manner reflects its release of a transmitter onto a postsynaptically located target neuron. As such, biochemical measures of neurotransmitter levels would be predicted to correspond to the activity changes occurring during electrophysiological recordings from neurons (Roth 1987). In several cases, such approaches have helped to define the physiological relevance of recorded neuron activity. One case in which this has proven valuable is in the analysis of firing pattern. For example, dopamine neurons, like many other cell types in the central nervous system, are capable of discharging trains of action potentials in two patterns of activity: single spiking and burst firing. However, their range of firing rates is comparatively restricted, with most cells firing only between 2 and 8 Hz. Nonetheless, information on the temporal relationship between spikes and bursts (Grace and Bunney 1984a) has been used in in vivo voltammetry studies to measure dopamine levels. Dopamine cells firing in bursts will release two to three times more neurotransmitter per spike from their terminals than those discharging at similar frequencies but in a steady firing pattern (Gonon 1988). Therefore, in this case, knowledge of the physiological firing pattern provided information to the electrochemist that resulted in the elucidation of the physiological consequence of burst firing in this system.
However, the extrapolation between biochemical and electrophysiological measures may not always be valid. Thus, recordings from single neurons may not necessarily reflect the activity across the population of neurons of interest. Therefore, a drug that exerts an action via activation of the nonfiring population of neurons may be overlooked if its actions are assessed on single spontaneously discharging neurons (Bunney and Grace 1978; Grace and Bunney 1984b). Furthermore, the response may be confined to a topographically defined subset of neurons mediating a particular response (e.g., a change in the activity of neurons regulating movement of the leg would not be predicted if the response involves a reaching movement of the arm). With respect to biochemical measurements, actions of transmitters at presynaptic terminals could dramatically alter the amount of neurotransmitter they release independent of neuronal discharge (e.g., Grace 1991). On the other hand, electrophysiological measurements enable researchers to examine responses that occur very rapidly. Indeed, a massive but transient activation of spike discharge in a neuronal system may evoke a substantial behavioral response, whereas biochemical measurements of neurotransmitter release performed over a long time course may dilute the impact of the transient event. Therefore, although the results obtained from each measure may not be directly comparable, the electrophysiological measurements are better optimized for detecting transient events.
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