This time in the Donders Beauty of the Brain Series, a picture of a hippocampal brain slice made with a confocal microscope is presented. This brain slice is of a transgenic mouse in which a subset (~20%) of the inhibitory brain cell express a green fluorescent protein (GFP). To show the outer contours of the slice, in blue the nuclei of all neurons in the slice are visualized via immunolabeling with DAPI. These hippocampal slices are made from 7 day old mouse pups and kept in culture for up to 3 weeks, where they continue to develop in a physiological manner. In our research, we use the slices to look at inhibitory axons and the formation of new inhibitory connections (synapses).

Neuronal circuits in our brain have an enormous capacity to adapt during development, when learning, or in response to injury or disease. In a healthy brain, changes in excitatory and inhibitory synapses are coordinated to preserve neuronal and network function. Experimental and computational studies have demonstrated that particularly inhibitory synapses, even though only ~15% of all synapses in the brain are inhibitory, are very important in controlling synaptic plasticity and shaping information processing in the brain (Herstel and Wierenga, 2021). Inhibitory synapses also represent a vulnerability of the brain. Impaired inhibitory signaling is at the basis of many neurodevelopmental and other brain disorders, including autism and early stages of Alzheimer’s disease. 

In the Wierenga lab we are interested in the role of inhibitory synapses at the molecular, cellular and network level. We study the molecular mechanisms underlying the formation and plasticity of inhibitory synapses using a combination of two-photon microscopy, electrophysiology and molecular approaches in brain slices. Our live imaging studies show that inhibitory synapses are incredibly dynamic. They can be formed or eliminated rapidly depending on local demand. We already unraveled some of the molecular signals that govern the formation of inhibitory synapses and identified an unexpected role for endocannabinoids in local coordination of excitatory and inhibitory synapses within dendrites (Hu et al., 2019).