Dismantling the Papez circuit for memory in rats

Abstract

Over the last 50 years, anatomical models of memory have repeatedly highlighted the hippocampal inputs to the mammillary bodies via the postcommissural fornix. Such models downplay other projections to the mammillary bodies, leaving them largely ignored. The present study challenged this dominant view by removing, in rats, the two principal inputs reaching the mammillary bodies: the postcommissural fornix from the hippocampal formation and Gudden's ventral tegmental nucleus. The principal mammillary body output pathway, the mammillothalamic tract, was disconnected in a third group. Only mammillothalamic tract and Gudden's ventral tegmental nucleus lesions impaired behavioral tests of spatial working memory and, in particular, disrupted the use of extramaze spatial landmarks. The same lesions also produced widespread reductions in immediate-early gene (c-fos) expression in a network of memory-related regions, not seen after postcommissural fornix lesions. These findings are inconsistent with previous models of mammillary body function (those dominated by hippocampal inputs) and herald a new understanding of why specific diencephalic structures are vital for memory.DOI: http://dx.doi.org/10.7554/eLife.00736.001

Mammilliothalamic tract lesions disrupt tests of visuo-spatial memory.

“…This contrasts with the more profound and enduring deficit seen in the radial-maze task (Experiment 3) and elsewhere in other maze-based tasks (e.g., Vann, 2013; Vann & Aggleton, 2003). The relative mildness of the deficit observed on the location task in Experiment 1 may in part reflect the lack of a navigational component.…”

Functional heterogeneity of the limbic thalamus: From hippocampal to cortical functions

“…As proposed earlier, the anterior thalamus appears to support hippocampal functions (Aggleton, 2012;Brown, 1999, 2006;Carlesimo et al, 2011), or, more properly, to provide a major contribution to an extended system encompassing not only the hippocampus proper but also the diencephalon and the cingulate region. This extended system corresponds to the Papez circuit, possibly enriched by midbrain inputs from the nucleus of Gudden (Dillingham et al, 2014;Vann, 2009Vann, , 2013. There is no doubt that the anterior thalamus occupies a cardinal position within this system, at the crossroad between direct and indirect hippocampal and midbrain inputs, consistent with a fundamental role in spatial cognition.…”

“…It is therefore ideally located to integrate information computed by hippocampal place cells with directional information, which explains why this region appears to be a major contributor in the neural circuitry supporting self-location (Barry and Burgess, 2014). Furthermore, recent advances concerning the functional role of the mammillary bodies are discussed in this issue (Dillingham et al, 2014), showing that the non-hippocampal inputs to the mammillary bodies (from the tegmental nucleus of Gudden, a midbrain structure) contribute to "hippocampal-dependent" spatial memory (Vann, 2013;Vann et al, 2011). Again, the anterior thalamus would appear as the critical node in the circuit where information from the hippocampus and the midbrain could be integrated.…”

The subiculum

“…Remarkably, this surgery had no apparent effect on matching-to-place in the water maze (Vann et al, 2011). One interpretation is that the mammillary body involvement in spatial memory is not reliant on the subiculum, rather it is dependent on other afferents, e.g., from Gudden's tegmental nucleus (Vann, 2013). Another implication is that the spared fornical fibers projecting to other sites, e.g., the anterior thalamic nuclei and prefrontal cortex, may support this form of spatial learning when the mammillary bodies are disconnected.…”

“…It is evident that the subiculum has a key role in these interactions, assuming that they depend on hippocampal efferents. A potential caveat is that the principal direction of functional control could be from these sites to the hippocampus (Vann, 2013). Even so, the subicular complex would still remain in center stage (see below).…”