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Chemical-LTP induce changes in the acetylation state of synaptic protein and PSD95 clustering in cultures of mice hippocampal neurons

Ricardo Sebastian Rivas

  • CABA,
  • Argentina
  • Sebastián Rivas ¹
  • , María Florencia Acutain ²
  • , Verónica Báez ²
  • , Ramiro Freudenthal ¹
  • 1 Instituto de Biociencias, Biotecnología y Biología traslacional-FCEN-UBA / CONICET
  • 2 Instituto de Biología Celular y Neurociencias-FMed-UBA-CONICET

Protein acetylation affects synaptic plasticity and memory, but its effects on synaptic composition are poorly understood. Previous work of our group shows a memory facilitation effect of an inhibitor of the cytoplasmic histone deacetylase 6. The literature reports an increase in the clustering of PSD95 after TSA treatment and also an augmented microtubule spine entry frequency after LTP induction in hippocampal neurons in culture.
We evaluate the changes induced by a high glycine LTP protocol (chLTP) in the PSD95, synapsin and acetylation clusters. The chLTP was applied to 18 DIV mice hippocampal neurons in culture and evaluated before treatment (ctrl), 0, 5, 15 and 45 minutes after it.
We found an increase in the fluorescence intensity, area and density of acetylation clusters after chLTP induction as well as an increase in the area and density of PSD95 clusters. Furthermore, the percentage of acetylated particles that colocalized with PSD95 was also increased, pointing that this change occurs in the PSD. In addition, we observed an increase in the proportion of small PSD95 particles 15 and 45 minutes after LTP induction. Finally, the puncta density of synapsin increased immediately after chLTP and puncta intensity diminished 15 minutes after it. This could be related to an LTP induced presynaptic vesicles accumulation and later depletion.
These findings show that learning-and-memory related mechanism as LTP affects protein acetylation state and composition at the PSD.