IIBBA   05544
INSTITUTO DE INVESTIGACIONES BIOQUIMICAS DE BUENOS AIRES
Unidad Ejecutora - UE
artículos
Título:
Knocking-down the NMDAR1 subunit in a limited amount of neurons in the rat hippocampus impairs learning
Autor/es:
CHELI V; ADROVER M; BLANCO C; FERRARI C; CORNEA A; PITOSSI F; EPSTEIN AL; JERUSALINSKY D
Revista:
JOURNAL OF NEUROCHEMISTRY
Referencias:
Año: 2006 p. 68 - 73
ISSN:
0022-3042
Resumen:
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 67% 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.
Keywords: herpes simplex vector, hippocampus, learning
and memory, NMDA receptors.