Hippocampal synaptic plasticity in mice devoid of cellular prion protein

• Published in: Brain research. Molecular brain research. Vol. 131; no. 1; pp. 58 - 64
• Main Authors: Maglio, Laura E., Perez, Mariela F., Martins, Vilma R., Brentani, Ricardo R., Ramirez, Oscar A.
• Format: Journal Article
• Language: English
• Published: Amsterdam Elsevier B.V 24.11.2004; Elsevier
• Subjects: Animals; Biological and medical sciences; Dentate gyrus; Dentate Gyrus - physiology; Dizocilpine Maleate - pharmacology; Encephalopathies; Excitatory Amino Acid Antagonists - pharmacology; Excitatory Postsynaptic Potentials - drug effects; Excitatory Postsynaptic Potentials - physiology; Fundamental and applied biological sciences. Psychology; Gene Expression; Hippocampus; In Situ Hybridization; Long-term potentiation; Long-Term Potentiation - physiology; Male; Mice; Mice, Inbred C57BL; Mice, Knockout; Neuronal Plasticity - physiology; NMDA receptor subunits; PrP c; PrPC Proteins - genetics; Receptors, N-Methyl-D-Aspartate - genetics; Vertebrates: nervous system and sense organs; Disorders of the nervous system; Dentate gyrus; Long-term potentiation; Encephalopathies; NMDA receptor subunits; PrP c; Hippocampus; Nervous system diseases; Rodentia; Central nervous system; Glutamate receptor; Subunit; Cerebral disorder; Vertebrata; Mammalia; PrPc; Mouse; Animal; Encephalopathy; Central nervous system disease; Synaptic plasticity; Prion; NMDA receptor
• ISSN: 0169-328X; 1872-6941
• DOI: 10.1016/j.molbrainres.2004.08.004

The cellular prion protein plays a role in the etiology of transmissible and inherited spongiform encephalopathies. However, the physiological role of the cellular prion protein is still under debate. Results regarding the synaptic transmission using the same strain of animals where the cellular prion protein gene was ablated are controversial, and need further investigation. In this work, we have studied the hippocampal synaptic transmission in mice devoid of normal cellular prion protein, and have shown that these animals present an increased excitability in this area by the lower threshold (20 Hz) to generate long-term potentiation (LTP) in hippocampal dentate gyrus when compared to wild-type animals. The mice devoid of normal cellular prion protein are also more sensitive to the blocking effects of dizocilpine and 2-amino-5-phosphonopentanoic acid on the hippocampal long-term potentiation generation. In situ hydridization experiments demonstrated overexpression of the mRNAs for the N-methyl- d-aspartate (NMDA) receptor NR2A and NR2B subunits in mice devoid of normal cellular prion protein. Therefore, our results indicate that these animals have an increased hippocampal synaptic plasticity which can be explained by a facilitated glutamatergic transmission. The higher expression of specific N-methyl- d-aspartate receptor subunits may account for these effects.