For proper functioning of neurons, excitatory and inhibitory synaptic inputs should be well attuned. We recently discovered that coordination between excitation and inhibition is regulated locally within the dendrites of CA1 pyramidal neurons. We found that when dendrites receive strong input from clustered excitatory synapses, they can trigger the growth of a new inhibitory synapse via retrograde endocannabinoid signaling (Hu, Kruijssen et al. Cell Reports 2019). Here we aim to determine how the dendrite integrates multiple signals to actively maintain a local coordination between excitatory and inhibitory inputs. We will also examine whether dendrites can coordinate activity dependent removal of inhibitory synapses.
The PhD student will use a combination of electrophysiology and two-photon microscopy in CA1 pyramidal cells in organotypic slices of transgenic mice to study activity dependent growth and shrinkage of dendritic inhibitory synapses. In addition, the student will employ a CRISPR/Cas9 gene editing approach to monitor recruitment of labeled proteins to newly formed inhibitory synapses.