Local translation in presynaptic terminals: Proteins carry out most of the functions in cells, including neurons, which are one of the most morphologically complex cell types in the body. This poses challenges for how proteins can be supplied to remote regions where connections (synapses) are made with other neurons. One solution to the neuron protein-supply problem involves the local synthesis of proteins from messenger RNA (mRNA) molecules located at or near synapses. Hafner et al. used RNA sequencing methods and superresolution microscopy to show that axon terminals contain hundreds of mRNA molecules as well as the machinery needed for protein synthesis. Furthermore, the axon terminals were able to use these components to make proteins that participate in synaptic transmission. Science , this issue p. eaau3644

Parvalbumin expressing (PV+) GABAergic interneurons are fast spiking neurons that provide powerful but relatively short-lived inhibition to principal excitatory cells in the brain. They play a vital role in feedforward and feedback synaptic inhibition, preventing run away excitation in neural networks. Hence, their dysfunction can lead to hyperexcitability and increased susceptibility to seizures. PV+ interneurons are also key players in generating gamma oscillations, which are synchronized neural oscillations associated with various cognitive functions. PV+ interneuron are particularly vulnerable to aging and their degeneration has been associated with cognitive decline and memory impairment in dementia and Alzheimer’s disease (AD). Overall, dysfunction of PV+ interneurons disrupts the normal excitatory/inhibitory balance within specific neurocircuits in the brain and thus has been linked to a wide range of neurodevelopmental and neuropsychiatric disorders. This review focuses on the role of dysfunctional PV+ inhibitory interneurons in the generation of epileptic seizures and cognitive impairment and their potential as targets in the design of future therapeutic strategies to treat these disorders. Recent research using cutting-edge optogenetic and chemogenetic technologies has demonstrated that they can be selectively manipulated to control seizures and restore the balance of neural activity in the brains of animal models. This suggests that PV+ interneurons could be important targets in developing future treatments for patients with epilepsy and comorbid disorders, such as AD, where seizures and cognitive decline are directly linked to specific PV+ interneuron deficits.