Neuronal Activity Regulates Blood-Brain Barrier Efflux Transport through Endothelial Circadian Genes.

The blood vessels in the central nervous system (CNS) have a series of unique properties, termed the blood-brain barrier (BBB), which stringently regulate the entry of molecules into the brain, thus maintaining proper brain homeostasis. We sought to understand whether neuronal activity could regulate BBB properties. Using both chemogenetics and a volitional behavior paradigm, we identified a core set of brain endothelial genes whose expression is regulated by neuronal activity. In particular, neuronal activity regulates BBB efflux transporter expression and function, which is critical for excluding many small lipophilic molecules from the brain parenchyma. Furthermore, we found that neuronal activity regulates the expression of circadian clock genes within brain endothelial cells, which in turn mediate the activity-dependent control of BBB efflux transport. These results have important clinical implications for CNS drug delivery and clearance of CNS waste products, including Aß, and for understanding how neuronal activity can modulate diurnal processes.

Powerhouse of the mind: mitochondrial plasticity at the synapse.

Neurons are highly polarized cells with extraordinary energy demands, which are mainly fulfilled by mitochondria. In response to altered neuronal energy state, mitochondria adapt to enable energy homeostasis and nervous system function. This adaptation, also called mitochondrial plasticity, can be observed as alterations in the form, function and position. The primary site of energy consumption in neurons is localized at the synapse, where mitochondria are critical for both pre- and postsynaptic functions. In this review, we will discuss molecular mechanisms regulating mitochondrial plasticity at the synapse and how they contribute to information processing within neurons.