Neuroanatomical investigations of the projections of the Papez circuit, with an emphasis on connections to the diencephalon


The projections of the extended hippocampal formation are still to a surprising extent under-described and under-investigated, despite the Papez circuit having been first postulated in 1937.  James Papez originally proposed that “the hypothalamus, the anterior thalamic nuclei, the gyrus cinguli, the hippocampus and their interconnections constitute a harmonious mechanism which may elaborate the functions of central emotion, as well as participate in emotional expression”. This was a hugely influential concept and he correctly highlighted a major circuit critical for hippocampal function (though his emphasis on emotion proved somewhat misplaced).

In the pair of papers below, we describe some of the circuit anatomy of this region, focusing on the output regions of the hippocampal formation (especially subiculum), and how they project to the diencephalon in particular.

Anatomical pictures can be staggeringly beautiful, as in this example:


This shows that there is a segregation of the outputs from subiculum, with separate projections to the mammillary bodies and the anterior thalamic nuclei.

J Comp Neurol. 2013 Sep 1;521(13):2966-86. doi: 10.1002/cne.23325.

Segregation of parallel inputs to the anteromedial and anteroventral thalamic nuclei of the rat. [Download the paper]

Wright NFVann SDErichsen JTO’Mara SMAggleton JP.

Many brain structures project to both the anteroventral thalamic nucleus and the anteromedial thalamic nucleus. In the present study, pairs of different tracers were placed into these two thalamic sites in the same rats to determine the extent to which these nuclei receive segregated inputs. Only inputs from the laterodorsal tegmental nucleus, the principal extrinsic cholinergic source for these thalamic nuclei, showed a marked degree of collateralization, with approximately 13% of all cells labeled in this tegmental area projecting to both nuclei. Elsewhere, double-labeled cells were very scarce, making up ∼1% of all labeled cells. Three general patterns of anterior thalamic innervation were detected in these other areas. In some sites, e.g., prelimbic cortex, anterior cingulate cortex, and secondary motor area, cells projecting to the anteromedial and anteroventral thalamic nuclei were closely intermingled, with often only subtle distribution differences. These same projections were also often intermingled with inputs to the mediodorsal thalamic nucleus, but again there was little or no collateralization. In other sites, e.g., the subiculum and retrosplenial cortex, there was often less overlap of cells projecting to the two anterior thalamic nuclei. A third pattern related to the dense inputs from the medial mammillary nucleus, where well-defined topographies ensured little intermingling of the neurons that innervate the two thalamic nuclei. The finding that a very small minority of cortical and limbic inputs bifurcates to innervate both anterior thalamic nuclei highlights the potential for parallel information streams to control their functions, despite arising from common regions.

PMID: 23504917

J Comp Neurol. 2010 Jun 15;518(12):2334-54. doi: 10.1002/cne.22336.

Parallel but separate inputs from limbic cortices to the mammillary bodies and anterior thalamic nuclei in the rat. [Download the paper]

Wright NFErichsen JTVann SDO’Mara SMAggleton JP.

The proposal that separate populations of subicular cells provide the direct hippocampal projections to the mammillary bodies and anterior thalamic nuclei was tested by placing two different fluorescent tracers in these two sites. In spite of varying the injection locations within the mammillary bodies and within the three principal anterior thalamic nuclei and the lateral dorsal thalamic nucleus, the overall pattern of results remained consistent. Neurons projecting to the thalamus were localized to the deepest cell populations within the subiculum while neurons projecting to the mammillary bodies consisted of more superficially placed pyramidal cells within the subiculum. Even when these two cell populations become more intermingled, e.g., in parts of the intermediate subiculum, almost no individual cells were found to project to both diencephalic targets. In adjacent limbic areas, i.e., the retrosplenial cortex, postsubiculum, and entorhinal cortex, populations of cells that project to the anterior thalamic nuclei and mammillary bodies were completely segregated. This segregated pattern included afferents to those nuclei comprising the head-direction system. The sole exception was a handful of double-labeled cells, mainly confined to the ventral subiculum, that were only found after pairs of injections in the anteromedial thalamic nucleus and mammillary bodies. The projections to the anterior thalamic nuclei also had a septal-temporal gradient with relatively fewer cells projecting from the ventral (temporal) subiculum. These limbic projections to the mammillary bodies and anterior thalamus comprise a circuit that is vital for memory, within which the two major components could convey parallel, independent information.

PMID: 20437531

Author: Shane O'Mara

Neuroscientist, Psychologist, Writer

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