Evidence for the substantia nigra pars compacta as an essential component of a memory system independent of the hippocampal memory system

Cunha, Cláudio Da; Wietzikoski, Samantha; Wietzikoski, Evellyn Claudia; Miyoshi, Edmar; Ferro, Marcelo Machado; Anselmo-Franci, Janete Aparecida; Canteras, Newton S.

doi:10.1016/s1074-7427(03)00008-x

Cited by 86 publications

(60 citation statements)

References 30 publications

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“…These neurons were specifically labeled by tyrosine hydroxylase (TH). 21,22 We found no significant change in the number of TH-positive neurons in the substantia nigra pars compacta of bf mice at 10 mo of age (Fig. 1F).…”

Section: Resultsmentioning

confidence: 83%

Impairment of autophagosome-lysosome fusion in the buff mutant mice with the VPS33A^D251E mutation

Zhen

2015

Autophagy

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-associated membrane protein 1; LRO, lysosome-related organelle; MAP1LC3/LC3, microtubule-associated protein 1 light chain 3; MEF, mouse embryonic fibroblast; RFP, red fluorescent protein; SNARE, soluble Nethylmaleimide-sensitive attachment protein (SNAP) receptor; SQSTM1/p62, sequestosome 1; STX, syntaxin; TH, tyrosine hydroxylase; VAMP, vesicle associated membrane protein/synaptobrevin; VPS, vacuole protein sorting; WT, wild type.The HOPS (homotypic fusion and protein sorting) complex functions in endocytic and autophagic pathways in both lower eukaryotes and mammalian cells through its involvement in fusion events between endosomes and lysosomes or autophagosomes and lysosomes. However, the differential molecular mechanisms underlying these fusion processes are largely unknown. Buff (bf) is a mouse mutant that carries an Asp251-to-Glu point mutation (D251E) in the VPS33A protein, a tethering protein and a core subunit of the HOPS complex. Bf mice showed impaired spontaneous locomotor activity, motor learning, and autophagic activity. Although the gross anatomy of the brain was apparently normal, the number of Purkinje cells was significantly reduced. Furthermore, we found that fusion between autophagosomes and lysosomes was defective in bf cells without compromising the endocytic pathway. The direct association of mutant VPS33A D251E with the autophagic SNARE complex, STX17 (syntaxin 17)-VAMP8-SNAP29, was enhanced. In addition, the VPS33A D251E mutation enhanced interactions with other HOPS subunits, namely VPS41, VPS39, VPS18, and VPS11, except for VPS16. Reduction of the interactions between VPS33A Y440D and several other HOPS subunits led to decreased association with STX17. These results suggest that the VPS33A D251E mutation plays dual roles by increasing the HOPS complex assembly and its association with the autophagic SNARE complex, which selectively affects the autophagosome-lysosome fusion that impairs basal autophagic activity and induces Purkinje cell loss.

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Section: Resultsmentioning

confidence: 83%

Impairment of autophagosome-lysosome fusion in the buff mutant mice with the VPS33A^D251E mutation

Zhen

2015

Autophagy

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“…Both praxic and taxon strategies can be understood as a stimulus-response-based navigation (Redish, 1999). 1 Several studies have been designed to assess the use of spatial information as opposed to simple cue response in solving a navigational task, that is, the dissociation of a locale vs a taxon strategy (Packard et al, 1989;Packard and McGaugh, 1996;Pearce et al, 1998;Devan and White, 1999;Chang and Gold, 2003;Da Cunha et al, 2003). They have shown that hippocampal lesions impair the learning of spatial tasks, but have little or no effect in navigating toward visible goals.…”

Section: Parallel Navigation Systemsmentioning

confidence: 99%

A Computational Model of Parallel Navigation Systems in Rodents

Chavarriaga

Strösslin

Sheynikhovich

et al. 2005

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“…in the hippocampus or dorsal striatum) in the preference for place or S-R strategies (Whishaw et al 1987, Packard et al 1989, Pearce et al 1998, Da Cunha et al 2003. As mentioned previously, substantial evidence supports the idea that the hippocampus mediates spatial learning, whereas the dorsal striatum is involved in S-R learning (see Redish 1999, Packard and Knowlton 2002, White and McDonald 2002.…”

Section: Experimental Approaches Dissociating Parallel Navigation Sysmentioning

confidence: 67%

Competition between cue response and place response: a model of rat navigation behaviour

et al. 2005

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Different neural systems are involved in animal navigation depending on the type of task. Experimental studies support the idea that the hippocampus is necessary to learn a spatial representation required to navigate toward hidden goals (place response), whereas the dorsolateral striatum is involved in the learning of stimulus-response associations when navigating toward visible (or cued) goals. These systems compete for action selection according to the characteristics of the task, previous experience (e.g. training procedure) or endogenous factors. This paper reviews both experimental data on the theory of multiple memory systems involved in navigation, and a recent computational model of action selection based on the competition of place and cue responses learnt during training. The model implements separately the two types of response, i.e. place response and stimulus response. Furthermore, competition takes place to select which behaviour will actually be performed. The model was tested in a simulated environment using a protocol analogous to those used in experiments with animals.

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Evidence for the substantia nigra pars compacta as an essential component of a memory system independent of the hippocampal memory system

Cited by 86 publications

References 30 publications

Impairment of autophagosome-lysosome fusion in the buff mutant mice with the VPS33A^D251E mutation

Impairment of autophagosome-lysosome fusion in the buff mutant mice with the VPS33A^D251E mutation

A Computational Model of Parallel Navigation Systems in Rodents

Competition between cue response and place response: a model of rat navigation behaviour

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Evidence for the substantia nigra pars compacta as an essential component of a memory system independent of the hippocampal memory system

Cited by 86 publications

References 30 publications

Impairment of autophagosome-lysosome fusion in the buff mutant mice with the VPS33AD251E mutation

Impairment of autophagosome-lysosome fusion in the buff mutant mice with the VPS33AD251E mutation

A Computational Model of Parallel Navigation Systems in Rodents

Competition between cue response and place response: a model of rat navigation behaviour

Contact Info

Product

Resources

About

Impairment of autophagosome-lysosome fusion in the buff mutant mice with the VPS33A^D251E mutation

Impairment of autophagosome-lysosome fusion in the buff mutant mice with the VPS33A^D251E mutation