Neuron anatomically addressed

Classically, the central nervous system has been envisioned as a series of hard-wired synaptic connections between neurons, not unlike millions of telephone wires within thousands upon thousands of cables (Fig. 1—4). This idea has been referred to as the anatomically addressed nervous system. The anatomically addressed brain is thus a complex wiring diagram, ferrying electrical impulses to wherever the wire is plugged in (i.e., at a synapse). There are an estimated 100 billion neurons, which make over 100 trillion synapses, in a single human brain. 

The wrong neuronal wiring of the anatomically addressed nervous system could thus be quite problematic for proper brain functioning. 

Inhaled nicotine is efficiently delivered to the brain (see chapter by Benowitz, this volume) where it selectively interacts with its central targets, the neuronal nicotinic acetylcholine receptors (nAChRs). The multiple subtypes of uAChR (see chapter by Collins et al, this volume) all bind nicotine but with different affinities, depending on the subunit composition of the uAChR. Binding may result in activation or desensitisation of uAChRs, reflecting the temporal characteristics of nicotine dehvery and local concentration of nicotine. Another level of complexity of the actions of nicotine reflects the widespread and non-uniform distribution of uAChR subtypes within the brain, such that nicotine can influence many centrally regulated functions in addition to the reward systems. In this chapter, we address the consequences of nicotine interactions with nAChRs at the molecular, cellular and anatomical levels. We critically evaluate experimental approaches, with respect to their relevance to human smoking, and contrast the acute and chronic effects of nicotine. 

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