Laura Cocas

Start Year: 2019
Starting Institution: Santa Clara University
Project Title: The Role of Synaptic Adhesion Proteins in Neuronal Glial Connectivity and Myelination

NG2 cells are oligodendrocyte progenitor cells that express a chondroitin sulfate proteoglycan, and are one of the largest pools of dividing cells in the postnatal brain. NG2 cells express postsynaptic adhesion proteins, and the expression of these proteins is developmentally regulated in the brain, peaking during synapse formation. While many NG2 cells receive synapses from neurons, the function of these synapses is poorly understood. NG2 cells produce new oligodendrocytes that remyelinate axons after injury and in demyelinating diseases such as Multiple Sclerosis. Many NG2 cells differentiate into myelinating oligodendrocytes, and part of this differentiation process involves the loss of glutamatergic presynaptic inputs. We hypothesize that these synaptic adhesion proteins are critical for the formation of neuron to NG2 cell synapses and that their loss will lead to defects in the total number of neuron to NG2 synapses, as well as the strength of those synaptic connections and loss of myelin during developmental myelination. We will test these hypotheses by examining the number of neuron to NG2 synaptic connections in the hippocampus in mice with mutations in these synaptic adhesion proteins. We will determine whether these proteins are necessary for neuron to OPC synapse function by examining the strength and conduction velocity of these synaptic connections through whole cell patch clamp recordings in brain slices. We will examine spontaneous activity and evoked activity, measuring excitatory and inhibitory synaptic inputs onto NG2 cells. We will also induce LTP and examine the ability of NG2 cells to undergo LTP. We will examine the conduction velocity of the myelinated fibers of the hippocampus, as well as a loss of myelin using electron microscopy. This will allow us to determine whether these adhesion proteins are important for synaptic transmission in neuron to NG2 cell connections.


Associate Director