Functional anatomy of human hippocampal formation and related structures

Data on the internal organization, and neuronal connections of the human hippocampal formation and related structures of the limbic system are briefly reviewed. In the healthy brain, somatosensory, visual, and auditory input proceeds through neocortical core and belt fields to a variety of association areas, and from here the data is transported via long corticocortical pathways to the extended prefrontal association cortex. Tracts generated from this highest organization level of the brain guide the data via the frontal belt (premotor cortex) to the frontal core (primary motor area). The striatal and cerebellar loops provide the major routes for this data transfer. The main components of the limbic system (the hippocampal formation, the entorhinal region, and the amygdala) maintain a strategic position between the sensory and the motor association areas. Part of the stream of data from the sensory association areas to the prefrontal cortex branches off and eventually converges on the entorhinal region and the amygdala, These connections establish the afferent leg of the limbic loop. In addition, the limbic centers receive substantial input from nuclei processing viscerosensory information. The entorhinal region, the hippocampal formation, and the amygdala are densely interconnected. Important among these connections is the perforant path, which originates in the entorhinal cortex and projects to the hippocampal formation (fascia dentata, Ammon's horn, and subiculum). The subiculum projects to the amygdala, entorhinal region, mamillary nuclei, and anterior and midline thalamic nuclei. The hippocampal formation, the entorhinal region, and the amygdala generate the efferent leg of the limbic loop, which is directed toward the prefrontal cortex. Additional projections reach the key nuclei that control endocrine and autonomic functions. Furthermore, the amygdala exerts influence on all nonthalamic nuclei projecting in a nonspecific manner to the cerebral cortex (ie, the cholinergic magnocellular forebrain nuclei, the histaminergic tuberomamillary nucleus, the dopaminergic nuclei of the ventral tegmentum, the serotonergic anterior raphe nuclei, and the noradrenergic locus ceruleus). The limbic loop centers thus are in the unique strategic position to perform integration of exteroceptive sensory data of various sources with interoceptive stimuli from autonomic centers. Their efferent projections exert influence on both the prefrontal association cortex and the key centers controlling endocrine and autonomic functions.