
Molecular Mechanisms of recognition memory – study of mitochondrial NADH dehydrogenase II subunit and src kinase complex during visual imprinting in c
The major purpose of the project is to analyze molecular mechanisms of recognition memory of visual
imprinting in chicks. Strong converging evidence indicates that a restricted part of the chick forebrain, the
intermediate and medial part of the mesopallium (IMM) stores information acquired through imprinting. In the light
of this evidence for the localization of the memory trace, imprinting affords a powerful model for analyzing the neural
basis of memory [1].
Our recent data indicates that mitochondria of the left IMM, are involved in imprinting [2-4 ]. Recently we
have shown that in the left IMM 24h after training significant hypo methylation occurs with learning at 4 CpG
positions, including genes coding for NADH dehydrogenase II subunit(NADHII) and NADHIV subunits. NADHII
is mitochondrial genome coded only one protein, which exists outside of mitochondria and specifically interacts with
Src protein kinase [5]. This interaction takes place outside of mitochondria at excitatory synapses. NADHII acts as an
adaptor protein and links Src protein kinase with N-methyl-D-aspartate (NMDA) receptors and increases NMDA
receptor currents. Previously we have shown learning-specific up regulation NMDA NR2B subunits in the left IMM.
All these data rise an intriguing possibility of NADHII-Src protein kinase-NMDA receptor complex involvement in
imprinting.
The tasks of the projects are: (i) study of transcription changes 24h after imprinting in NADHII, NADHIV
(subjected to hypo methylation) and NADHI genes (not subjected to any significant changes in methylation); (ii) The
identification of other protein components in the NADHII-Src protein kinase - NMDA receptor complex. (iii) Study
of changes in the Src protein kinase and NMDA glutamate receptor subunits linked with NADHII 24h after training.
Immuprecipitation will be carried out by antibodies against NADHII. (iv) Study of changes in the NADHII and NMDA
glutamate receptor subunits linked with Src 24h after training. Immunoprecipitation will be carried out by antibodies
against Src. These experiments are analogous to Task (iii) and will be control and complement for it; (v) Study of
changes in Src protein kinase phosphorylation on 2 sites: one involved in its activation and another in its inhibition.
Obtained results will shed a new light on a molecular mechanisms of involvement NADHII-Src protein kinaseNMDA receptor complex in long-term memory of imprinting
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