The legacy of the silver methods and the new anatomy of the basal forebrain: Implications for neuropsychiatry and drug abuse

The first part of the paper highlights the remarkable legacy of the silver methods, with special emphasis on the travails and opportunities offered by the various Nauta methods and their modifications. When the tracer methods based on axoplasmic flow were introduced in the early 1970s, they were exploited on a backdrop of a basic anatomical framework, which had already been established through the tracing of the major CNS pathways by the aid of the silver methods, especially the widely used Nauta–Gygax methods and their modifications. Some of the silver methods that were developed in the late 1960s for the staining of degenerating boutons (e.g. the Fink–Heimer method and de Olmos cupric silver method) provided the necessary technical improvements that eventually led to a new and more productive way to look at the basal forebrain functional/anatomical organization; if it was not for the silver methods, we would in all likelihood still be promoting the nebulous notion of the substantia innominata rather than the concepts of the ventral striatopallidal system and the extended amygdala. The discovery and elaboration of these two macroanatomical systems symbolize what might deservedly be called the “new anatomy” of the basal forebrain. Following a review of the critical experiments which led to the development of the new anatomy of the basal forebrain, its topography in the human is reviewed in drawings of an abbreviated series of coronal sections. The discovery of the ventral striatopallidal system and its thalamic projection to the mediodorsal thalamus rather than to the ventral anterior‐ventral lateral thalamic complex ushered in the idea of parallel cortico‐subcortical reentrant circuits, which to a large extent has replaced the limbic system as a theoretical framework for neuropsychiatric disorders. The extended amygdala, which appears as a large ring formation around the internal capsule, is still controversial in some quarters, although it is slowly but surely making its way into the general neuroscience literature, especially in the field of addictive disorders. The ventral striatopallidal system and the extended amygdala are interwoven in a complex fashion with the basal nucleus of Meynert within the basal forebrain. Together, these three systems represent important output channels for so‐called “limbic” forebrain regions, especially orbitomedial prefrontal cortex and medial temporal lobe structures, which are increasingly implicated in major neuropsychiatric disorders.