Re-evaluating the role of the mammillary bodies in memory

School of Psychology, Cardiff University, Tower Building, 70 Park Place, Cardiff CF10 3AT, UK
Neuropsychologia (Impact Factor: 3.3). 07/2010; 48(8):2316-2327. DOI: 10.1016/j.neuropsychologia.2009.10.019
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Although the mammillary bodies were among the first brain regions to be implicated in amnesia, the functional importance of this structure for memory has been questioned over the intervening years. Recent patient studies have, however, re-established the mammillary bodies, and their projections to the anterior thalamus via the mammillothalamic tract, as being crucial for recollective memory. Complementary animal research has also made substantial advances in recent years by determining the electrophysiological, neurochemical, anatomical and functional properties of the mammillary bodies. Mammillary body and mammillothalamic tract lesions in rats impair performance on a number of spatial memory tasks and these deficits are consistent with impoverished spatial encoding. The mammillary bodies have traditionally been considered a hippocampal relay which is consistent with the equivalent deficits seen following lesions of the mammillary bodies or their major efferents, the mammillothalamic tract. However, recent findings suggest that the mammillary bodies may have a role in memory that is independent of their hippocampal formation afferents; instead, the ventral tegmental nucleus of Gudden could be providing critical mammillary body inputs needed to support mnemonic processes. Finally, it is now apparent that the medial and lateral mammillary nuclei should be considered separately and initial research indicates that the medial mammillary nucleus is predominantly responsible for the spatial memory deficits following mammillary body lesions in rats.

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Available from: Seralynne D Vann,
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    • "Gudden's tegmental nuclei comprise two distinct divisions (Petrovicky, 1971): the dorsal tegmental nucleus (DTg) and the ventral tegmental nucleus (VTg). In the rat brain, their connections with the mammillary bodies are segregated so that DTg innervates the lateral mammillary nucleus, supporting navigation through its influence upon the head direction system (Vann and Aggleton, 2004; Vann, 2005, 2011; Taube, 2007; Clark et al., 2013; Dwyer et al., 2013), while VTg innervates the medial mammillary nucleus (Hayakawa and Zyo, 1984; Allen and Hopkins, 1989; Hopkins, 2005), again supporting spatial learning in the rat (Vann, 2009, 2013), but in ways that are different to the DTg pathway (Vann, 2010; Dillingham et al., 2015). It is known that some cells in both VTg and DTg of the rat are positive for markers of GABA, leuenkephalin , and glutamate (Allen and Hopkins, 1989; Wirtshafter and Stratford, 1993; Gonzalo-Ruiz et al., 1999), which are also found on some neurons that innervate the mammillary bodies. "
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    ABSTRACT: The principal projections to the mammillary bodies arise from just two sites, Gudden's tegmental nuclei (dorsal and ventral nuclei) and the hippocampal formation (subiculum and pre/postsubiculum). The present study sought to compare the neurochemical properties of these mammillary body inputs in the rat, with a focus on calcium-binding proteins. Neuronal calretinin (CR) immunoreactivity was sparse in Gudden's tegmental nuclei and showed no co-localization with neurons projecting to the mammillary bodies. In contrast, many of the ventral tegmental nucleus of Gudden cell that project to the mammillary bodies were parvalbumin (PV)-positive whereas a smaller number of mammillary inputs stained for calbindin (CB). Only a few mammillary body projection cells in the dorsal tegmental nucleus of Gudden co-localized with PV and none co-localized with CB. A very different pattern was found in the hippocampal formation. Here, a large proportion of postsubiculum cells that project to the mammillary bodies co-localized with CR, but not CB or PV. While many neurons in the dorsal and ventral subiculum projected to the mammillary bodies, these cells did not co-localize with the immunofluorescence of any of the three tested proteins. These findings highlight marked differences between hippocampal and tegmental inputs to the rat mammillary bodies as well as differences between the medial and lateral mammillary systems. These findings also indicate some conserved neurochemical properties in Gudden's tegmental nuclei across rodents and primates.
    Frontiers in Neuroanatomy 09/2015; 9. DOI:10.3389/fnana.2015.00103 · 3.54 Impact Factor
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    • "As already mentioned, the lateral mammillary nuclei showed differences between both groups. In this regard, lesion studies support the idea of the mammillary bodies being involved in spatial memory [17]. Additionally, lateral mammillary nuclei has been related to rapid new spatial learning, as it lesion produce mild impairments in this task execution [47]. "
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    ABSTRACT: Several studies suggest a prefrontal cortex involvement during the acquisition and consolidation of spatial memory, suggesting an active modulating role at late stages of acquisition processes. Recently, we have reported that the prelimbic and infralimbic areas of the prefrontal cortex, among other structures, are also specifically involved in late phases of spatial memory extinction. This study aimed to evaluate whether the inactivation of the prelimbic area of the prefrontal cortex impaired spatial memory extinction. For this purpose, male Wistar rats were implanted bilaterally with cannulae into the prelimbic region of the prefrontal cortex. Animals were trained during five consecutive days in a hidden platform task and tested for reference spatial memory immediately after the last training session. One day after completing the training task, bilateral infusion of the GABAA receptor agonist muscimol was performed before the extinction protocol was carried out. Additionally, cytochrome c oxidase histochemistry was applied to map the metabolic brain activity related to the spatial memory extinction under prelimbic cortex inactivation. Results show that animals acquired the reference memory task in the water maze, and the extinction task was successfully completed without significant impairment. However, analysis of the functional brain networks involved by cytochrome oxidase activity interregional correlations showed changes in brain networks between the group treated with muscimol as compared to the saline-treated group, supporting the involvement of the mammillary bodies at a the late stage in the memory extinction process. Copyright © 2015. Published by Elsevier B.V.
    Behavioural brain research 03/2015; 287. DOI:10.1016/j.bbr.2015.03.033 · 3.03 Impact Factor
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    • "Importantly, the patients with MD lesions who were amnesic showed additional damage to the MTT. Lesion to the MTT has been long known to be a strong predictor of anterograde amnesia (Vann, 2010; Carlesimo et al., 2011). While a strong relation exists between MTT damage and anterograde memory impairment (Cipolotti et al., 2008), no study has directly contrasted MTT and thalamic integrity with regard to episodic memory performance. "
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    ABSTRACT: Effects of thalamic nuclei damage and related white matter tracts on memory performance are still debated. This is particularly evident for the medio-dorsal thalamus which has been less clear in predicting amnesia than anterior thalamus changes. The current study addresses this issue by assessing 7 thalamic stroke patients with consistent unilateral lesions focal to the left medio-dorsal nuclei for immediate and delayed memory performance on standard visual and verbal tests of anterograde memory, and over the long-term (>24 h) on an object-location associative memory task. Thalamic patients showed selective impairment to delayed recall, but intact recognition memory. Patients also showed accelerated forgetting of contextual details after a 24 h delay, compared to controls. Importantly, the mammillothalamic tract was intact in all patients, which suggests a role for the medio-dorsal nuclei in recall and early consolidation memory processes.
    Frontiers in Behavioral Neuroscience 09/2014; 8:320. DOI:10.3389/fnbeh.2014.00320 · 3.27 Impact Factor
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