Structure-Function Relationships of Experience-Dependent Spine Plasticity

Icahn School Of Medicine At Mount Sinai, New York NY

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Abstract

The objective of this proposal is to determine the key functional properties at the single-spine level that are associated with experience-dependent gain and loss of spines. Spines are known to appear and disappear in an experience-dependent manner throughout life. Such changes have key implications for behaviors by physically rearranging the circuit connectivity. However, the specific functional properties of individual spines in vivo that are associated with gain and loss of spines are not known. Such information is important for a better understanding of and interventions into brain disorders accompanying spine deficits. A classical model of experience-dependent plasticity, ocular dominance plasticity in the primary visual cortex, accompanies gain and loss of spines during monocular deprivation in addition to the cellular changes in ocular preference. Recent advances in two-photon calcium imaging techniques have enabled direct observation of single-spine activity in vivo, and highly specific and diverse functional properties (e.g. orientation preference) of individual spines were revealed. However, little is known to what extent the functional properties of spines are related to the experience-dependent gain and loss of spines. By fluorescent visualization of local calcium transient using a green genetically encoded fluorescent indicator (GCaMP6) and visualization of spine structure with a red fluorescent protein, simultaneous time-lapse structural and functional two-photon imaging of ocular dominance at the single spine level in vivo will be achieved to test the overarching hypothesis that specific functional properties of individual spines are associated with their experience-dependent gain and loss which collectively impact the plasticity of parent neurons' output. In aim1, the functional signatures at single spines associated with the experience-dependent spine gain will be determined. In aim2, functional properties of single spines that predict experience-dependent loss of spines will be identified. At the completion of this study, we will have determined for the first time the key functional properties of spines associated with their experience-dependent gain and loss. Such findings will serve as novel targets for the development of therapeutic approaches for functional recovery in the adult brain disorders.