Neuroanatomical correlates of genetic risk for obesity in children.

Obesity has a strong genetic component, with up to 20% of variance in body mass index (BMI) being accounted for by common polygenic variation. Most genetic polymorphisms associated with BMI are related to genes expressed in the central nervous system. At the same time, higher BMI is associated with neurocognitive changes. However, the direct link between genetics of obesity and neurobehavioral mechanisms related to weight gain is missing. Here, we use a large sample of participants (n > 4000) from the Adolescent Brain Cognitive Development cohort to investigate how genetic risk for obesity, expressed as polygenic risk score for BMI (BMI-PRS), is related to brain and behavioral measures in adolescents. In a series of analyses, we show that BMI-PRS is related to lower cortical volume and thickness in the frontal and temporal areas, relative to age-expected values. Relatedly, using structural equation modeling, we find that lower overall cortical volume is associated with higher impulsivity, which in turn is related to an increase in BMI 1 year later. In sum, our study shows that obesity might partially stem from genetic risk as expressed in brain changes in the frontal and temporal brain areas, and changes in impulsivity.

Synergistic excitability plasticity in cerebellar functioning.

The cerebellum, a universal processor for sensory acquisition and internal models, and its association with synaptic and nonsynaptic plasticity have been envisioned as the biological correlates of learning, perception, and even thought. Indeed, the cerebellum is no longer considered merely as the locus of motor coordination and its learning. Here, we introduce the mechanisms underlying the induction of multiple types of plasticity in cerebellar circuit and give an overview focusing on the plasticity of nonsynaptic intrinsic excitability. The discovery of long-term potentiation of synaptic responsiveness in hippocampal neurons led investigations into changes of their intrinsic excitability. This activity-dependent potentiation of neuronal excitability is distinct from that of synaptic efficacy. Systematic examination of excitability plasticity has indicated that the modulation of various types of Ca2+ - and voltage-dependent K+ channels underlies the phenomenon, which is also triggered by immune activity. Intrinsic plasticity is expressed specifically on dendrites and modifies the integrative processing and filtering effect. In Purkinje cells, modulation of the discordance of synaptic current on soma and dendrite suggested a novel type of cellular learning mechanism. This property enables a plausible synergy between synaptic efficacy and intrinsic excitability, by amplifying electrical conductivity and influencing the polarity of bidirectional synaptic plasticity. Furthermore, the induction of intrinsic plasticity in the cerebellum correlates with motor performance and cognitive processes, through functional connections from the cerebellar nuclei to neocortex and associated regions: for example, thalamus and midbrain. Taken together, recent advances in neuroscience have begun to shed light on the complex functioning of nonsynaptic excitability and the synergy.