What Are the Limitations to Place Cell Research

Single-cell recordings allow the study of information processing by individual neurons of a particular region within the brain with enough temporal precision to correlate activity of individual neurons with particular behaviors. The power of single-cell recordings is limited, however, by the facts that the electrodes sample a very small selection of the neurons from only one subregion of the brain, monitoring numerous brain regions simultaneously is difficult (but see Lee et al., 2004), and the anatomical locations and connections of the recorded neurons can be defined only in general terms. For example, the CA1 hippocampus contains roughly 400,000 pyramidal cells (Rosenzweig and Barnes, 2003); even the published ''world record'' for number of place cells recorded simultaneously of 141 cells (Wilson and McNaughton, 1993) manages only a small sample of the hippocampus. Furthermore, single-cell recordings are highly invasive and cannot be done in human subjects (although see Ekstrom et al., 2003).

Electrophysiological recording of single-cells is not the only means of studying neuronal activity. For example, the fMRI technique is a noninvasive way to study activation over the entire human brain, while the subject thinks about a computer screen (for applications relevant to aging, see Chapter 12 by Small). However, the spatial precision of fMRI is far from individual neurons, the trials must be averaged, which reduces temporal precision, and the subjects are restricted in behavior. Recently in animal research, gene activation studies have proved capable of studying the activity of single neurons simultaneously across many brain regions. cFos, Arc, and Homer are genes whose expression is induced immediately following neuronal activity. Through immunostaining, these genes provide a marker for which neurons have been activated during a particular time period prior to sacrifice of the rat. A drawback of the immediate-early gene technique to study neuronal activation is that the rat must be sacrificed in order to get the information. This means that one cannot measure changes in activity across different behavioral settings or across learning, as one can do with in vivo electrophysiology.

Monitoring of place cells contributes one piece to our understanding of cognitive aging through their insight into spatial memory, but there is convincing evidence that the hippocampus handles more than just spatial information (reviewed by Eichenbaum et al., 1999). Important studies have, therefore, examined the activity of single cells during a nonspatial task in aged rabbits (for example, McEchron et al., 2001). Moreover, to reap the full benefit of the single-cell recording technique, place cell results must be placed in the context of well-researched age-related behavioral impairments and deteriorations to hippocampal connectivity and plasticity (for reviews of this, see Foster, 1999; Wu et al., 2002; Rosenzweig and Barnes, 2003; Wilson, 2005). Many of these neuroanatomical changes to the aging brain are discussed in Chapter 32 by Bizon and Nicolle. Each technique provides its own insight into the mechanisms underlying age-related memory impairments; by putting many technique pieces together, we can begin to understand why the aging brain is sometimes impaired.

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Blood Pressure Health

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