Biology subjects

Koekkoek, S. K. E.

Publications and source records attributed to Koekkoek, S. K. E..

3 recordsLinked to original sources

bioRxiv2024

Acute Aerobic Exercise Enhances Associative Learning in Active but not Sedentary Individuals

IntroductionPhysical exercise has repeatedly been reported to have advantageous effects on brain functions, including learning and memory formation. However, objective tools to measure such effects are often lacking. Eyeblink conditioning is a well-characterised method for studying the neural basis of associative learning. As such, this paradigm has potential as a tool to assess to what extent exercise affects one of the most basic forms of learning. Until recently, however, using this paradigm for testing human subjects in their daily life was technically challenging. As a consequence, no studies have investigated how exercise affects eyeblink conditioning in humans. Here we hypothesize that acute aerobic exercise is associated with improved performance in eyeblink conditioning. Furthermore, we explored whether the effects of exercise differed for people with an active versus a sedentary lifestyle. MethodsWe conducted a case-control study using a smartphone-based platform for conducting neurometric eyeblink conditioning in healthy adults aged between 18 - 40 years (n = 36). Groups were matched on age, sex, and education level. Our primary outcome measures included the amplitude and timing of conditioned eyelid responses over the course of eyeblink training. As a secondary measure, we studied the amplitude of the unconditioned responses. ResultsAcute exercise significantly enhanced the acquisition of conditioned eyelid responses; however, this effect was only true for individuals with an active lifestyle. No statistically significant effects were established for timing of the conditioned responses and amplitude of the unconditioned responses. DiscussionThis study highlights a facilitative role of acute aerobic exercise in associative learning and emphasises the importance of accounting for lifestyle when investigating the acute effects of exercise on brain functioning.

neuroscience↗

bioRxiv2023

Vascular abnormalities in heart and brain are associated with cardiovascular and neurological symptoms in a novel mouse model for Williams syndrome

Williams syndrome is a developmental disorder caused by a microdeletion entailing the loss of a single copy of 25-27 genes on chromosome 7q11.23. Patients suffer from cardiovascular and neuropsychological symptoms. Structural abnormalities of the cardiovascular system in Williams syndrome have been attributed to the hemizygous loss of the elastin (ELN) gene. In contrast, the neuropsychological consequences of Williams syndrome, including sensorimotor deficits, hypersociability and cognitive impairments, have been mainly attributed to altered expression of transcription factors like LIMK1, GTF2I and GTF2IRD1, while the potential impact of altered cerebrovascular function has been largely overlooked. To study the relationship between Williams syndrome mutations and vascularization of both the heart and brain, we generated a mouse model carrying a relatively long microdeletion (LD) that includes the Ncf1 gene, thereby minimizing the confounding impact of hypertension. LD mice had elongated and tortuous aortas but, unlike Eln haploinsufficient mice, showed no signs of structural cardiac hypertrophy. Remarkably, LD mice also displayed structural abnormalities in coronary and brain vessels, including disorganized extracellular matrices. Importantly, LD mice faithfully replicated both cardiovascular and neuropsychological symptoms observed in patients. The phenotype was even more comprehensive than former models, with structure-function correlations evident in aberrant auditory and motor behaviors resembling those in patients with Williams syndrome. Together, our findings suggest that not only cardiovascular but also neuropsychological symptoms in Williams syndrome may be driven in part by vascular abnormalities affecting both heart and brain. Significance StatementWilliams syndrome is caused by microdeletion of 25-27 genes on chromosome 7q11.23, resulting in cardiovascular and neuropsychological symptoms. It remains unclear how the affected genes interact and whether cardiovascular deficits influence brain function. We developed and characterized a mouse model with the longest Williams syndrome microdeletion to date. This model reveals interactions between genes that can be compensatory or additive: haploinsufficiency of Ncf1 may counteract the cardiac hypertrophy caused by Eln deletion, while vascular defects that are potentially due to Eln haploinsufficiency extend to the brain and may worsen neuropsychological symptoms. Our findings support the hypothesis that structural vascular deficits putatively contribute to both cardiac and cognitive phenotypes in Williams syndrome, opening new avenues for understanding and treating this syndrome.

systems biology↗

bioRxiv2021

Behavioral and molecular underpinnings of performance variability in eyeblink conditioning in male and female mice

The functional and molecular sources of behavioral variability in mice are not fully understood. As a consequence, the predominant use of male mice has become a standard in animal research, under the assumption that males are less variable than females. Similarly, to homogenize genetic background, neuroscience studies have almost exclusively used the C57BL/6 (B6) strain. Here, we examined individual differences in performance in the context of associative learning. We performed delayed eyeblink conditioning while recording locomotor activity in mice from both sexes in two strains (B6 and B6CBAF1). Further, we used a C-FOS immunostaining approach to explore brain areas involved in eyeblink conditioning across subjects and correlate them with behavioral performance. We found that B6 male and female mice show comparable variability in this task and that females reach higher learning scores. We found a strong positive correlation across sexes between learning scores and voluntary locomotion. C-FOS immunostainings revealed positive correlations between C-FOS positive cell density and learning in the cerebellar cortex, as well as multiple previously unreported extra-cerebellar areas. We found consistent and comparable correlations in eyeblink performance and C-fos expression in B6 and B6CBAF1 females and males. Taken together, we show that differences in motor behavior and activity across brain areas correlate with learning scores during eyeblink conditioning across strains and sexes.

neuroscience↗