Understanding SNARE protein mediation of neuromodulator release from dense-core vesicles

How are long term memories encoded in the hippocampus?

Project Abstract

The Lochner lab seeks to understand the biochemical underpinnings of long-
term memory formation in a region of the brain called the hippocampus. Neurons, core cells in the brain, communicate at junctions known as synapses. Activity-dependent structural and chemical changes at synapses allow neurons to strengthen intercellular communication. This process, referred to as synaptic strengthening, underlies the creation of long-term memories in the hippocampus. One component of synaptic strengthening involves the synaptic release of neuromodulatory proteins from dense-core vesicles (DCVs). Specialized SNARE protein complexes that drive membrane fusion mediate synaptic neuromodulatory protein release. Much has been elucidated regarding SNARE complexes in other biological settings, including neurotransmitter release from synaptic vesicles. However, limited information exists as to SNARE mediation of DCV release in hippocampal neurons. The Lochner lab employs molecular cloning techniques, disruption of gene expression, and super-resolution fluorescence microscopy to identify key proteins involved in the secretion of neuromodulators from DCVs. The syntaxin family of SNARE proteins is of particular interest because the positions of these proteins determine the sites of DCV release. These findings will extend knowledge of the biochemical mechanisms involved in learning, memory, and pathological processes.

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