Research Projects

Memories of life events are vital for survival. In neurons, higher spine density supports memory, while spine loss links to memory loss. Recent studies challenge old ideas, showing spine loss is not just due to less activity or local plasticity, but due to poor synchrony with nearby synapses. This underlines the role of coordinated spine clustering. Also, plasticity rules differ by compartment, with unique traits in basal versus apical dendrites. So, spine arrangement during plasticity is crucial for encoding memory and may reflect memory content in neural circuits. Due to the high energy demand during spine remodeling and synaptic plasticity, cellular metabolism is gaining increasing attention. Spine formation needs local ATP and calcium buffering, both provided by Mitochondria (Mt). However, Mt are unevenly spread in compartments. Many presynaptic boutons lack them, while postsynaptically, one Mt can serve several spines. This raises questions on how dendrites meet energy demands for spines. In culture, Mt form stable ~30 μm clusters along dendrites, unlike in axons, and show compartment-specific shapes: fused in apical tufts, fragmented in basal or oblique branches. In living mice under stress, Mt gain/loss strongly links with spine formation/elimination. Together, these findings highlight a spatiotemporal cross-correlation between Mt and spine clusters, and may potentially represent memory content at the dendritic level. Furthermore, unlike electrical stimulation, optogenetic activation of channelrhodopsin (ChR)-expressing neurons alters calcium-dependent plasticity processes and boosts neurotransmitter release. Recent advances in engineering ion-specific opsins, such as calcium-permeable ChR (CapChR), open new ways to fine-tune intracellular calcium levels. Our theoretical work suggests that activating CapChR can induce calcium-dependent plasticity at spines, offering a tool to artificially induce plasticity. Experimental testing of CapChR-induced plasticity is important. It will reveal how spine and Mt clusters reorganize over time, and how this controlled plasticity compares with natural, behavior-driven changes. This could uncover fundamental rules of how neurons encode and store memories and provide new strategies to repair or boost plasticity in disease conditions. In the proposed research, we hypothesize that the cross-clustering of dendritic spines and Mt along dendrites is a representation of memory content. We will record how these dendritic clusters change during plasticity triggered by behavior tasks or targeted optogenetic stimulation. By measuring the cross-correlation and relative ratios of mitochondria and spines across different dendritic compartments and in neurons with and without induced plasticity, we hope to uncover compartment-specific rules for memory storage. These insights will guide future research on how stress and brain disorders disrupt these patterns and affect learning and memory.