Dissociation of genotype-dependent cognitive and motor behavior in a strain of aging mice devoid of the prion protein

Janner, Daiane R.; Lima, Emanuelle V. de; Silva, Rachel T. da; Clarke, Julia R.; Linden, Rafael

doi:10.1016/j.bbr.2021.113386

Cited by 2 publications

(1 citation statement)

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“…Our results showed no motor alternations in the Prnp ZH3/ZH3 mice, but they need more sessions to learn the task compared to controls. Previous publications also showed any motor alterations in two different knock-out strains [45,65,67]. However, Nazor et al observed changes just in mice older than 95 days [61].…”

Section: Discussionmentioning

confidence: 89%

Analysis of co-isogenic prion protein deficient mice reveals behavioral deficits, learning impairment, and enhanced hippocampal excitability

et al. 2022

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Background Cellular prion protein (PrPC) is a cell surface GPI-anchored protein, usually known for its role in the pathogenesis of human and animal prionopathies. However, increasing knowledge about the participation of PrPC in prion pathogenesis contrasts with puzzling data regarding its natural physiological role. PrPC is expressed in a number of tissues, including at high levels in the nervous system, especially in neurons and glial cells, and while previous studies have established a neuroprotective role, conflicting evidence for a synaptic function has revealed both reduced and enhanced long-term potentiation, and variable observations on memory, learning, and behavior. Such evidence has been confounded by the absence of an appropriate knock-out mouse model to dissect the biological relevance of PrPC, with some functions recently shown to be misattributed to PrPC due to the presence of genetic artifacts in mouse models. Here we elucidate the role of PrPC in the hippocampal circuitry and its related functions, such as learning and memory, using a recently available strictly co-isogenic Prnp0/0 mouse model (PrnpZH3/ZH3). Results We performed behavioral and operant conditioning tests to evaluate memory and learning capabilities, with results showing decreased motility, impaired operant conditioning learning, and anxiety-related behavior in PrnpZH3/ZH3 animals. We also carried in vivo electrophysiological recordings on CA3-CA1 synapses in living behaving mice and monitored spontaneous neuronal firing and network formation in primary neuronal cultures of PrnpZH3/ZH3 vs wildtype mice. PrPC absence enhanced susceptibility to high-intensity stimulations and kainate-induced seizures. However, long-term potentiation (LTP) was not enhanced in the PrnpZH3/ZH3 hippocampus. In addition, we observed a delay in neuronal maturation and network formation in PrnpZH3/ZH3 cultures. Conclusion Our results demonstrate that PrPC promotes neuronal network formation and connectivity. PrPC mediates synaptic function and protects the synapse from excitotoxic insults. Its deletion may underlie an epileptogenic-susceptible brain that fails to perform highly cognitive-demanding tasks such as associative learning and anxiety-like behaviors.

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Section: Discussionmentioning

confidence: 89%

Analysis of co-isogenic prion protein deficient mice reveals behavioral deficits, learning impairment, and enhanced hippocampal excitability

et al. 2022

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Behavioral deficits, learning impairment, and enhanced hippocampal excitability in co-isogenic Prnp^ZH3/ZH3 mice

Matamoros‐Angles

Hervera

Soriano

et al. 2021

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The cellular prion protein (PrPC) has been associated with numerous cellular processes, such as cell differentiation and neurotransmission. Moreover, it was recently demonstrated that some functions were misattributed to PrPC since results were obtained from mouse models with genetic artifacts. Here we elucidate the role of PrPC in the hippocampal circuitry and its related functions, like learning and memory, using the new strictly co-isogenic Prnp0/0 mouse. Behavioral and operant conditioning tests were performed to evaluate memory and learning capabilities. In vivo electrophysiological recordings were carried out at CA3-CA1 synapses in living behaving mice, and spontaneous neuronal firing and network formation were monitored in primary neuronal cultures of PrnpZH3/ZH3vs. wild-type mice. Results showed decreased motility, impaired operant conditioning learning, and anxiety-related behavior in PrnpZH3/ZH3 animals. PrPC absence enhanced susceptibility to high-intensity stimulations and kainate-induced seizures. However, long-term potentiation (LTP) was not enhanced in the PrnpZH3/ZH3 hippocampus. In addition, we observed a delay in neuronal maturation and network formation in PrnpZH3/ZH3 cultures. In conclusion, PrPC mediates synaptic function and protects the synapse from excitotoxic insults. Its deletion might evoke a susceptible epileptogenic brain that would fail to perform highly cognitive-demanding tasks such as associative learning and anxiety-like behaviors.

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Dissociation of genotype-dependent cognitive and motor behavior in a strain of aging mice devoid of the prion protein

Cited by 2 publications

References 20 publications

Analysis of co-isogenic prion protein deficient mice reveals behavioral deficits, learning impairment, and enhanced hippocampal excitability

Analysis of co-isogenic prion protein deficient mice reveals behavioral deficits, learning impairment, and enhanced hippocampal excitability

Behavioral deficits, learning impairment, and enhanced hippocampal excitability in co-isogenic Prnp^ZH3/ZH3 mice

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Dissociation of genotype-dependent cognitive and motor behavior in a strain of aging mice devoid of the prion protein

Cited by 2 publications

References 20 publications

Analysis of co-isogenic prion protein deficient mice reveals behavioral deficits, learning impairment, and enhanced hippocampal excitability

Analysis of co-isogenic prion protein deficient mice reveals behavioral deficits, learning impairment, and enhanced hippocampal excitability

Behavioral deficits, learning impairment, and enhanced hippocampal excitability in co-isogenic PrnpZH3/ZH3 mice

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Behavioral deficits, learning impairment, and enhanced hippocampal excitability in co-isogenic Prnp^ZH3/ZH3 mice