Partial unilateral inactivation of the dorsal hippocampus impairs spatial memory in the MWM

Cimadevilla, José Manuel; Miranda, Rubén; López, Laudino; Árias, Jorge L.

doi:10.1016/j.cogbrainres.2005.09.001

Cited by 21 publications

(24 citation statements)

References 29 publications

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“…The use of different procedures and training protocols can perhaps explain different degrees of impairment. In addition, unilateral blockade also alters consolidation, confirming previously published results (Cimadevilla et al, 2005).…”

Section: Discussionsupporting

confidence: 89%

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Bilateral and Unilateral Hippocampal Inactivation Did not Differ in their Effect on Consolidation Processes in the Morris Water Maze

Cimadevilla

Miranda

López

et al. 2008

International Journal of Neuroscience

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Consolidation processes were studied in the rat by using functional inactivation techniques. Previous results showed that unilateral hippocampal inactivation alters consolidation. It is not clear if bilateral treatments increase the impairment. Wistar rats were trained in the Morris water maze during 4 consecutive days. Subjects received saline or tetrodotoxin in the dorsal hippocampus 1 min after training. Results showed that bilateral as well as unilateral treatments impair consolidation to the same degree, as shown by the mean latency to reach the platform. In both cases, the impairment is only visible in the first trial of the session following the blockade.

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Section: Discussionsupporting

confidence: 89%

“…Recently, it was reported that partial unilateral inactivation of the dorsal hippocampus in the Morris water maze (MWM) slightly interferes with consolidation of spatial information (Cimadevilla et al, 2005). This introduces a new question: Can bilateral interventions impair consolidation processes more severely than unilateral treatments?…”

Section: Introductionmentioning

confidence: 99%

Bilateral and Unilateral Hippocampal Inactivation Did not Differ in their Effect on Consolidation Processes in the Morris Water Maze

Cimadevilla

Miranda

López

et al. 2008

International Journal of Neuroscience

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“…Another explanation for this observation might be neural reorganization or partial regeneration of the lesioned hippocampus during the recovery phase. In contrast to our present findings, unilateral inactivation of the hippocampal formation with tetrodoxin, the sodium channel blocker, is known to induce spatial learning deficit in tasks such as Carousel maze (Cimadevilla et al, 2000;Kubik and Fenton, 2005) or Morris water maze (Cimadevilla et al, 2005). However, these reports support the finding that NMDA induced hippocampal damage does not represent a model to inactivate the structure, but rather excitotoxicity triggered neurodegeneration.…”

Section: The Lesion Did Not Spread To Other Structures and Did Not Incontrasting

confidence: 57%

Rat intra-hippocampal NMDA infusion induces cell-specific damage and changes in expression of NMDA and GABAA receptor subunits

et al. 2016

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Excessive stimulation of NMDA receptors with glutamate or other potent agonists such as NMDA leads to excitotoxicity and neural injury. In this study, we aimed to provide insight into an animal model of brain excitotoxic damage; single unilateral infusion of NMDA at mild dose into the hippocampal formation. NMDA infusion induced chronic, focal neurodegeneration in the proximity of the injection site. The lesion was accompanied by severe and progressive neuroinflammation and affected preferentially principal neurons while sparing GABAergic interneurons. Furthermore, the unilateral lesion did not cause significant impairment of spatial learning abilities. Finally, GluN1 and GluN2B subunits of NMDA receptor were significantly upregulated up to 3 days after the NMDA infusion, while GABAA 5 subunit was downregulated at 30 days after the lesion. Taken together, a single infusion of NMDA into the hippocampal formation represents an animal model of excitotoxicity-induced chronic neurodegeneration of principal neurons accompanied by severe neuroinflammation and subunit specific changes in NMDA and GABAA receptors. Highlights:1. The infusion of NMDA induced degeneration of hippocampal principal cells. 2. Neurodegeneration was accompanied with progressive and severe neuroinflammation. 3. The lesion did not induce loss of GABAergic interneurons. 4. GluN1 and GluN2B subunits of NMDA receptor were upregulated at early time points.5. GABA A receptor α5 subunit was downregulated at 30 days after the lesion. ABSTRACTExcessive stimulation of NMDA receptors with glutamate or other potent agonists such as NMDA leads to excitotoxicity and neural injury. In this study, we aimed to provide insight into an animal model of brain excitotoxic damage; single unilateral infusion of NMDA at mild dose into the hippocampal formation. NMDA infusion induced chronic, focal neurodegeneration in the proximity of the injection site. The lesion was accompanied by severe and progressive neuroinflammation and affected preferentially principal neurons while sparing GABAergic interneurons. Furthermore, the unilateral lesion did not cause significant impairment of spatial learning abilities. Finally, GluN1 and GluN2B subunits of NMDA receptor were significantly upregulated up to 3 days after the NMDA infusion, while GABA A α5 subunit was downregulated at 30 days after the lesion. Taken together, a single infusion of NMDA into the hippocampal formation represents an animal model of excitotoxicity-induced chronic neurodegeneration of principal neurons accompanied by severe neuroinflammation and subunit specific changes in NMDA and GABA A receptors.

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“…The specific engagement of the left hippocampus in spatial short-term memory suggested by Poe et al (2000), who used hippocampal tetracaine inactivation in aged rats, does not contradict this view. During retrieval, however, the operations necessary for memory recall might preferentially require the participation of the right hippocampus, as shown by Cimadevilla et al (2005) and Cimadevilla and Arias (2008). Indeed, whereas right inactivation before the probe trial impaired retrieval, performance was still above chance.…”

Section: Right Versus Left Hippocampus: Inactivation Studymentioning

confidence: 89%

Hippocampal‐dependent spatial memory functions might be lateralized in rats: An approach combining gene expression profiling and reversible inactivation

et al. 2009

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The hippocampus is involved in spatial memory processes, as established in a variety of species such as birds and mammals including humans. In humans, some hippocampal-dependent memory functions may be lateralized, the right hippocampus being predominantly involved in spatial navigation. In rodents, the question of possible lateralization remains open. Therefore, we first microdissected the CA1 subregion of the left and right dorsal hippocampi for analysis of mRNA expression using microarrays in rats having learnt a reference memory task in the Morris water-maze. Relative to untrained controls, 623 genes were differentially expressed in the right hippocampus, against only 74 in the left hippocampus, in the rats that had learnt the hidden platform location. Thus, in the right hippocampus, 299 genes were induced, 324 were repressed, and about half of them participate in signaling and transport, metabolism, and nervous system functions. In addition, most differentially expressed genes associated with spatial learning have been previously related to synaptic plasticity and memory. We then subjected rats to unilateral (left or right) or bilateral reversible functional inactivations in the dorsal hippocampus; lidocaine was infused either before each acquisition session or before retrieval of a reference spatial memory in the Morris water maze. We found that after drug-free acquisition, right or bilateral lidocaine inactivation (vs. left, or bilateral phosphate buffered saline (PBS) infusions) of the dorsal hippocampus just before a delayed (24 h) probe trial impaired performance. Conversely, left or bilateral hippocampus inactivation (vs. right, or bilateral PBS infusions) before each acquisition session weakened performance during a delayed, drug-free probe trial. Our data confirm a functional association between transcriptional activity within the dorsal hippocampus and spatial memory in the rat. Further, they suggest that there could be a leftward bias of hippocampal functions in engram formation or information transfer, and a rightward bias in spatial memory storage/retrieval processes.

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Partial unilateral inactivation of the dorsal hippocampus impairs spatial memory in the MWM

Cited by 21 publications

References 29 publications

Bilateral and Unilateral Hippocampal Inactivation Did not Differ in their Effect on Consolidation Processes in the Morris Water Maze

Bilateral and Unilateral Hippocampal Inactivation Did not Differ in their Effect on Consolidation Processes in the Morris Water Maze

Rat intra-hippocampal NMDA infusion induces cell-specific damage and changes in expression of NMDA and GABAA receptor subunits

Hippocampal‐dependent spatial memory functions might be lateralized in rats: An approach combining gene expression profiling and reversible inactivation

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