V-036 | The Cdk5/p35 complex regulates working memory and neuronal activation in a mouse model of Attention Deficit Hyperactivity Disorder

Cognition, Behavior, and Memory
Author: Gimena Berardo | Email: gimenaberardo4@gmail.com

Gimena Berardo^1°, Florencia Dadam^1°2°,Osvaldo Martín Basmadjian^1°, María Gabriela Paglini^1°3°

^1° Instituto de Investigación Médica Mercedes y Martín Ferreyra, INIMEC-CONICET-UNC
^2° Facultad de Psicologia.Universidad Nacional de Córdoba
^3° Instituto de Virología “Dr. José María Vanella”, In.Vi.V.-CONICET-UNC

Attention-Deficit/Hyperactivity Disorder (ADHD) is a neurodevelopmental condition characterized by hyperactivity, impulsivity, and memory deficits. One of the crucial symptoms of ADHD is working memory (WM) impairment, a cognitive function essential for temporary storage and manipulation of information during complex tasks such as planning, decision making, and problem solving. WM relies heavily on the prefrontal cortex, which coordinates attention and executive control, as well as the hippocampus, which is involved in the formation of long-term memory.
Using transgenic mice lacking p35 (p35KO), the activating subunit of Cdk5, which models key ADHD features, we studied the role of the complex Cdk5/p35 in WM and neuronal activity in ADHD-relevant brain areas, considering potential sex differences. We used p35KO and wild-type (WT) mice (21-25 days postnatal) to assess WM using the Y-maze task and neuronal activity in relevant brain areas with c-FOS immunostaining
p35KO male mice exhibited altered WM compared to WT. Furthermore, a lower number of c-FOS positive cells were observed in different brain nuclei of both, the prefrontal cortex and the hippocampus, indicating altered neuronal activation in these regions.
In conclusion, our study emphasizes the importance of the Cdk5/p35 complex in WM processes and suggests that dysfunction in these brain areas contributes to WM deficits, which significantly impairs individual’s ability to plan and execute complex cognitive tasks.