Double dissociation of function within the hippocampus: A comparison of dorsal, ventral, and complete hippocampal cytotoxic lesions.

Bannerman, David M.; Yee, B. K.; Good, Mark Andrew; Heupel, M. J.; Iversen, Susan D.; Rawlins, J. N. P.

doi:10.1037/0735-7044.113.6.1170

Cited by 359 publications

(296 citation statements)

References 53 publications

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“…Environmental enrichment had a positive effect upon the motor and sensorimotor behavior of the mutant mice, but did not exert a beneficial effect upon their MWM performance, a dissociation which may suggest that the aberrant phenotype caused by the PLC-b1 null mutation is mediated by distinct pathways differentially responsive to the effects of enrichment. Alternatively, given the dissociation we observe in the effects of environmental enrichment, it is of significant interest that learning and memory are particularly susceptible to dorsal hippocampal manipulations, 42,43 while locomotor activity and PPI, which are modulated, but not mediated, by the hippocampus (in that its involvement is not critical to performance of the behavior), have been shown to be much more susceptible to ventral hippocampal lesions. 44 Environmental enrichment may be regionally specific, providing another potential explanation for the discrepancy in the enrichment effect; however, further experiments would be required in order to resolve this question.…”

Section: Discussionmentioning

confidence: 98%

Phospholipase C-β1 knockout mice exhibit endophenotypes modeling schizophrenia which are rescued by environmental enrichment and clozapine administration

et al. 2007

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Phospholipase C-b1 (PLC-b1) is a rate-limiting enzyme implicated in postnatal-cortical development and neuronal plasticity. PLC-b1 transduces intracellular signals from specific muscarinic, glutamate and serotonin receptors, all of which have been implicated in the pathogenesis of schizophrenia. Here, we present data to show that PLC-b1 knockout mice display locomotor hyperactivity, sensorimotor gating deficits as well as cognitive impairment. These changes in behavior are regarded as endophenotypes homologous to schizophrenialike symptoms in rodents. Importantly, the locomotor hyperactivity and sensorimotor gating deficits in PLC-b1 knockout mice are subject to beneficial modulation by environmental enrichment. Furthermore, clozapine but not haloperidol (atypical and typical antipsychotics, respectively) rescues the sensorimotor gating deficit in these animals, suggesting selective predictive validity. We also demonstrate a relationship between the beneficial effects of environmental enrichment and levels of M1/M4 muscarinic acetylcholine receptor binding in the neocortex and hippocampus. Thus we have demonstrated a novel mouse model, displaying disruption of multiple postsynaptic signals implicated in the pathogenesis of schizophrenia, a relevant behavioral phenotype and associated gene-environment interactions.

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Section: Discussionmentioning

confidence: 98%

Phospholipase C-β1 knockout mice exhibit endophenotypes modeling schizophrenia which are rescued by environmental enrichment and clozapine administration

et al. 2007

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“…On the days of PCP administration (days 7, 9, and 11), only the dentate gyrus of the hippocampus is still developing (Bayer et al, 1993). Since this structure is crucial for spatial learning (Bannerman et al, 1999;Moser et al, 1995) and allocentric orientation (Czéh et al, 2001), it seems possible that injury to the hippocampus by perinatal injection of NMDA antagonists leads to the same behavioral anomalies observed after surgical lesions of the dorsal hippocampus (Pouzet et al, 2002), and consequently after impairing processes that enable the rats to retain spatial information (Morris et al, 1982;Morris and Frey, 1997). Since the striatum develops earlier than the hippocampus (Bayer et al, 1993), and is consequently not altered by our perinatal treatment with PCP, the animals can still use idiocentric strategies, characterized by large loop-shaped swim paths, and following the edge of the pool.…”

Section: Discussionmentioning

confidence: 99%

Spatial Memory Deficits Induced by Perinatal Treatment of Rats with PCP and Reversal Effect of D-Serine

Andersen

Pouzet

2004

Neuropsychopharmacol

119

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It has been suggested that perinatal treatment with the noncompetitive N-methyl-D-aspartate (NMDA) receptor antagonist phencyclidine (PCP) induces transient neurodegeneration in the limbic and cortical structures of rats. Since dysfunction of these structures is associated with cognitive deficits in patients with schizophrenia, we studied the effects of subchronic treatment with PCP in perinatal rats with respect to spatial reference, reversal, and spatial working memories using the Morris water maze task in adulthood. In addition, we investigated the effect of D-serine, which has clinical relevance for the treatment of cognitive deficits in patients with schizophrenia. Our goal was to develop a neurodevelopmental model with predictive validity for the cognitive dysfunction described in patients with schizophrenia. Male and female Sprague-Dawley rats were treated with either saline or PCP (8.7 mg/kg s.c.) on days 7, 9, and 11, postnatal, and the long-term behavioral effects were investigated in adulthood. Male PCP-treated rats were slightly impaired during the spatial reference memory task, but strongly impaired during the reversal and spatial working memory tasks. Female rats were not significantly affected by this treatment. This cognitive deficit was reversed by chronic treatment with D-serine. We suggest that this model mimics some of the cognitive deficits of patients with schizophrenia and might be appropriate for the screening of putative antipsychotic agents for the treatment of these cognitive deficits.

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“…The dorsal CA1 hippocampus is implicated in the processing of contextual information (Bannerman et al, 2002;Bannerman et al, 1999;Kjelstrup et al, 2002;Moser et al, 1993;Moser and Moser, 1998). Therefore, to evaluate if GABA B(1a) receptors within the dorsal CA1 region of the hippocampus are required for precise contextual memory and limiting generalized fear, animals received infusions of CGP 36216 or vehicle into the dorsal CA1 immediately after context fear training (Figure 4a) or 5 min before testing (Figure 4d).…”

Section: Hippocampal Gaba B(1a) Receptors Constrain Contextual Fear Gmentioning

confidence: 99%

“…GABA B(1a) receptors are located at glutamatergic terminals in neocortical and hippocampal pyramidal neurons (Jacobson et al, 2007b;Shaban et al, 2006;Vigot et al, 2006). Given the involvement of these structures both in processing contextual information (Bannerman et al, 2002;Bannerman et al, 1999;Kjelstrup et al, 2002;Moser et al, 1993;Moser and Moser, 1998), and in fear generalization (Cullen et al, 2014;Cullen et al, 2015), the current study was designed to explore when presynaptic GABA B(1a) receptors contribute to contextual discrimination, thereby constraining generalized fear. In order to assess this, C57BL/6 male mice received cannula implants aimed at the lateral ventricle and were infused with a GABA B(1a) receptor-specific antagonist CGP 36216.…”

Section: Introductionmentioning

confidence: 99%

Hippocampal GABAB(1a) Receptors Constrain Generalized Contextual Fear

Lynch

Winiecki

Gilman

et al. 2016

Neuropsychopharmacol

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Many anxiety disorders are characterized by generalization of fear responses to neutral or ambiguous stimuli. Therefore, a comprehensive understanding of the mechanisms contributing to generalized fear is essential for formulating successful treatments for anxiety disorders. Previous research shows that GABA-mediated presynaptic inhibition has a critical role in cued fear generalization, as animals with genetically deleted presynaptic GABA B(1a) receptors cannot discriminate between CS+ and CS − tones. Work from our laboratory has further identified that GABA B(1a) receptors are necessary for maintaining contextual memory precision, thereby constraining generalized contextual fear. We previously found that GABA B(1a) KO mice show generalized fear to a neutral context 24 h after training, but not 2 h after training. A similar pattern was observed with object location and recognition, suggesting that this receptor subtype affects consolidation and/or retrieval of precise contextual and spatial memories. Here we sought to specifically examine the involvement of GABA B(1a) receptors in consolidation or retrieval of a precise fear memory. To do so, we infused a selective GABA B(1a) receptor antagonist, CGP 36216, intracerebroventricularly (ICV), or locally into the dorsal hippocampus, ventral hippocampus, or anterior cingulate cortex (ACC), during consolidation and retrieval of context fear training. Blockade of GABA B(1a) receptors through ICV, dorsal hippocampal, or ventral hippocampal infusions 'after' training (consolidation) resulted in fear generalization to the neutral context when mice were tested 24, but not 6 h after training. Post-training infusions of CGP into the ACC, however, did not promote generalized fear. In addition, ICV, dorsal hippocampal, ventral hippocampal, or ACC infusions immediately 'before' testing (retrieval) did not result in context fear generalization. These data suggest that GABA-mediated presynaptic inhibition is not critical for retrieval of precise contextual memory, but rather has an important role in the long-term consolidation of precise contextual memories and constrains generalized fear responses.

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Double dissociation of function within the hippocampus: A comparison of dorsal, ventral, and complete hippocampal cytotoxic lesions.

Cited by 359 publications

References 53 publications

Phospholipase C-β1 knockout mice exhibit endophenotypes modeling schizophrenia which are rescued by environmental enrichment and clozapine administration

Phospholipase C-β1 knockout mice exhibit endophenotypes modeling schizophrenia which are rescued by environmental enrichment and clozapine administration

Spatial Memory Deficits Induced by Perinatal Treatment of Rats with PCP and Reversal Effect of D-Serine

Hippocampal GABAB(1a) Receptors Constrain Generalized Contextual Fear

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