Understanding mechanisMS responsible for the regulation of presynaptic strengths on a dendritic tree in rat hippocampal networks

Abstract

Information transmission and storage in the brain is majoritively encoded by two main components of a neuron – axon and dendrite. Terminals and release sites of axons pair with spines on their dendritic counterparts forming synapses. Structurally, a synapse has two components – a presynaptic release site on an axon and a complementary postsynaptic receptive site on the spine of a dendrite. The release site is characterized by clusters of vesicles sitting at axonal compartments called boutons whereas the postsynaptic side is defined by a set of receptor/voltage-gated channels present on the corresponding spine surface. The strengths of these components, termed as pre and postsynaptic strengths, are stipulated mainly by the release probability of vesicles and number of receptors on the spine. These strengths are found to be fairly heterogeneous throughout the network. But the mechanisms by which these strengths are modified and regulated are not well discerned. Recently, another type of cells called astrocytes which previously were considered to be playing a supportive role are gaining recognition for their subtle involvement in synaptic transmission and strength regulation. Consequently, the view that astrocytes indeed form a communicative framework across different synapses for global strength regulation is emerging. The project broadly aims at understanding the mechanisms underlying this strength regulation in pyramidal hippocampal cells and the role of astrocytes in the same. In particular, we tested the hypothesis that astrocytes control the heterogeneity of presynaptic strengths of multiple synapses received by a postsynaptic neuron. We validated the use of an optical imaging approach using the FM 1-43 styryl dye for effectively monitoring the release probabilities of multiple synapses received by excitatory neurons. With this technique, we set out to examine the effects of pharmacological inhibition of astrocyte Calcium signaling in primary hippocampal cell cultures. All the experimental accomplishments and difficulties faced during the course of project are interpreted and discussed in this dissertation.