Research Project: role of 5-HT2A receptors in cognitive flexibility and memory interference during a spatial working memory task.

CARLOS PRETELL; JUAN BELFORTE; NOELIA WEISSTAUB

huerta grande

Congreso; XXVIII Congreso Anual de la Sociedad Argentina de Investigaciones en neurocienicas; 2013

Sociedad Argentina de Neurociencias

Our ability to adjust our behavior to dynamic changes in the environment is called "cognitive flexibility" and it is part of the repertoire of executive functions. Memory interference is the result of competing memory traces. Both mechanisms are postulated to depend on the activity of the Prefrontal Cortex. Clinical and pre clinical data support a role of the serotonergic system (5-HTS) in cognitive flexibility and memory interference. The 5-HT2a receptor (5-HT2AR) it is one of the most important post-synaptic receptors of the 5-HTS and highly expressed in cortical regions and the limbic system. One of the main problems addressing the role of 5-HT2AR in cognitive functions is the lack of specific drugs. We are using a genetically modified mouse model to study the role of the 5-HT2AR in a spontaneous alternation task. Spontaneous alternation paradigms model the natural tendency of rodents to flexibly shift between different spatial options and it is a good paradigm to simultaneously address behavioral flexibility and proactive memory interference. 5-HT2AR knock-out mice (htr2a -/-) show a deficit in working memory (without preservative responses) when measured with the Y maze spontaneous alternation task. Immunohistochemical analysis of various regions after completion of the behavioral task showed increased expression of c-fos in htr2a-/- mice compared  with controls suggesting that lack of 5-HT2A protein alter brain reactivity during a particular class of working memory task.