University of Wisconsin investigators will use cellular imaging in laboratory cultures of neurons to explore how regulation of certain neuronal structures may affect brain plasticity,” the development of new neural network connections in the brain.
Brain cells (neurons) communicate by passing neurotransmitters from one cell to another. When a neurotransmitter travels down one neuron’s axon, it is released into a minute space (called the “synaptic junction”) and binds to receptors on a neighboring neuron’s dendrite. Axons and dendrites branch out extensively, creating an estimated 10 trillion synaptic junctions in the human brain. These synaptic junctions hold the potential for creating myriad neural networks. Dendrites have tiny protrusions, called dendritic spines. Spine shapes vary and change in response to activation. Spine shape directly affects the efficiency of neuronal synaptic communication. Large spines are associated with stronger synaptic connections. A stronger response by dendritic spines, termed “long-term potentiation,” is an experimental model of memory formation. Understanding how spine shapes are regulated, according to the University of Wisconsin researchers, may provide fundamental insight into how memory-related brain plasticity occurs and how plasticity may be altered in developmental disorders and cognitive diseases, such as Alzheimer’s.
Their initial evidence suggests that regulation of spine shapes occurs through a direct route from the neuronalcell body to the synapse via “microtubules.” These are long, hollow tubes that transport material within neurons. The researchers hypothesize that microtubules remodel dendritic spines in response to changes in neuronal activity. They will test this hypothesis using total internal reflection fluorescence microscopy (TIRFM) in laboratory cultures of cortical and hippocampal neurons, while manipulating neuronal activity. They also will use two-photon confocal microscopy in cortical and hippocampal brain slices to determine if microtubule invasion of dendritic spines occurs in an intact brain tissue preparation.
Significance: The results eventually may lead to a new understanding of how memory-related changes in brain plasticity occur and reveal targets for genetic and pharmacologic treatments for developmental and cognitive disorders.