Knocking-down the NMDAR1 subunit in a limited amount of neurons in the rat hippocampus impairs learning.
Amplicon vectors derived from herpes simplex virus type 1 were built to modify NMDA receptors by expressing antisense RNA for the essential NR1 subunit. Their ability to modify endogenous levels of NR1 was tested in cultures of rat embryo neocortical neurons. We studied behaviour and tested for expression in adult rats injected with those vectors into the dorsal hippocampus to find out which cells and how many appear involved in memory formation. Rats injected with vectors expressing NR1 antisense performed significantly worse than control rats in an inhibitory avoidance task. Immunohistochemistry was performed in brain slices from the same animals. The transduced cells represented 6-7% of pyramidal neurons in CA1, showing that a single gene knockdown of NR1 in a small number of neurons significantly impaired memory formation. Perhaps neurons undergoing synaptic plasticity are more susceptible to NR1 knockdown, and hence NMDAR are particularly required in those neurons undergoing synaptic plasticity during learning, or perhaps, and more likely, there is not a high level of redundancy in the hippocampal circuits involved, leading to the idea that a certain level of NR1 expression/availability appears necessary for memory formation in most of CA1 pyramidal neurons.
Cheli
V
V
Institute of Cellular Biology and Neuroscience Professor E De Robertis, School of Medicine, University of Buenos Aires, Argentina.
Adrover
M
M
Blanco
C
C
Ferrari
C
C
Cornea
A
A
Pitossi
F
F
Epstein
A L
AL
Jerusalinsky
D
D
D000818:Animals; D002478:Cells, Cultured; D015870:Gene Expression; D005822:Genetic Vectors; D049452:Green Fluorescent Proteins / Q000235:genetics; D018259:Herpesvirus 1, Human / Q000235:genetics; D006624:Hippocampus / Q000166:cytology / Q000502:physiology*; D015151:Immunoblotting; D007150:Immunohistochemistry; D007858:Learning / Q000502:physiology*; D008297:Male; D008568:Memory / Q000502:physiology; D018613:Microscopy, Confocal; D009474:Neurons / Q000502:physiology*; D016372:RNA, Antisense / Q000235:genetics; D051381:Rats; D017208:Rats, Wistar; D016194:Receptors, N-Methyl-D-Aspartate / Q000235:genetics / Q000502:physiology*; D011993:Recombinant Fusion Proteins; D014162:Transfection
D049452:Green Fluorescent Proteins; D016372:RNA, Antisense; D016194:Receptors, N-Methyl-D-Aspartate; D011993:Recombinant Fusion Proteins