structural plasticity

Homeostatic structural plasticity of neuronal connectivity triggered by optogenetic stimulation

Ever since Bliss and Lømo discovered the phenomenon of long-term potentiation (LTP) in rabbit dentate gyrus in the 1960s, Hebb’s rule—neurons that fire together wire together—gained popularity to explain learning and memory. Accumulating evidence, however, suggests that neural activity is homeostatically regulated. Homeostatic mechanisms are mostly interpreted to stabilize network dynamics. However, recent theoretical work has shown that linking the activity of a neuron to its connectivity within the network provides a robust alternative implementation of Hebb’s rule, although entirely based on negative feedback. In this setting, both natural and artificial stimulation of neurons can robustly trigger network rewiring. We used computational models of plastic networks to simulate the complex temporal dynamics of network rewiring in response to external stimuli. In parallel, we performed optogenetic stimulation experiments in the mouse anterior cingulate cortex (ACC) and subsequently analyzed the temporal profile of morphological changes in the stimulated tissue. Our results suggest that the new theoretical framework combining neural activity homeostasis and structural plasticity provides a consistent explanation of our experimental observations.

Structural plasticity by neurotrophins and Tolls in Drosophila

Imaging memory consolidation in wakefulness and sleep

New memories are initially labile and have to be consolidated into stable long-term representations. Current theories assume that this is supported by a shift in the neural substrate that supports the memory, away from rapidly plastic hippocampal networks towards more stable representations in the neocortex. Rehearsal, i.e. repeated activation of the neural circuits that store a memory, is thought to crucially contribute to the formation of neocortical long-term memory representations. This may either be achieved by repeated study during wakefulness or by a covert reactivation of memory traces during offline periods, such as quiet rest or sleep. My research investigates memory consolidation in the human brain with multivariate decoding of neural processing and non-invasive in-vivo imaging of microstructural plasticity. Using pattern classification on recordings of electrical brain activity, I show that we spontaneously reprocess memories during offline periods in both sleep and wakefulness, and that this reactivation benefits memory retention. In related work, we demonstrate that active rehearsal of learning material during wakefulness can facilitate rapid systems consolidation, leading to an immediate formation of lasting memory engrams in the neocortex. These representations satisfy general mnemonic criteria and cannot only be imaged with fMRI while memories are actively processed but can also be observed with diffusion-weighted imaging when the traces lie dormant. Importantly, sleep seems to hold a crucial role in stabilizing the changes in the contribution of memory systems initiated by rehearsal during wakefulness, indicating that online and offline reactivation might jointly contribute to forming long-term memories. Characterizing the covert processes that decide whether, and in which ways, our brains store new information is crucial to our understanding of memory formation. Directly imaging consolidation thus opens great opportunities for memory research.

Imaging the influences of sensory experience on visual system circuit development

Using a combination of in vivo imaging of neuronal circuit functional and structural dynamics, we have investigated the mechanisms by which patterned neural activity and sensory experience alter connectivity in the developing brain. We have identified, in addition to the long-hypothesized Hebbian structural plasticity mechanisms, a kind of plasticity induced by the absence of correlated firing that we dubbed “Stentian plasticity”. In the talk I will discuss the phenomenology and some mechanistic insights regarding Stentian mechanisms in brain development. Further, I will show how glia may have a key role in circuit remodeling during development. These studies have led us to an appreciation of the importance of neuron-glia interactions in early development and the ability of patterned activity to guide circuit wiring.

Brief Sensory Deprivation Triggers Cell Type-Specific Structural and Functional Plasticity in Olfactory Bulb Neurons

Can alterations in experience trigger different plastic modifications in neuronal structure and function, and if so, how do they integrate at the cellular level? To address this question, we interrogated circuitry in the mouse olfactory bulb responsible for the earliest steps in odor processing. We induced experience-dependent plasticity in mice of either sex by blocking one nostril for one day, a minimally invasive manipulation that leaves the sensory organ undamaged and is akin to the natural transient blockage suffered during common mild rhinal infections. We found that such brief sensory deprivation produced structural and functional plasticity in one highly specialized bulbar cell type: axon-bearing dopaminergic neurons in the glomerular layer. After 24 h naris occlusion, the axon initial segment (AIS) in bulbar dopaminergic neurons became significantly shorter, a structural modification that was also associated with a decrease in intrinsic excitability. These effects were specific to the AIS-positive dopaminergic subpopulation because no experience-dependent alterations in intrinsic excitability were observed in AIS-negative dopaminergic cells. Moreover, 24 h naris occlusion produced no structural changes at the AIS of bulbar excitatory neurons, mitral/tufted and external tufted cells, nor did it alter their intrinsic excitability. By targeting excitability in one specialized dopaminergic subpopulation, experience-dependent plasticity in early olfactory networks might act to fine-tune sensory processing in the face of continually fluctuating inputs. (https://www.jneurosci.org/content/41/10/2135)

Local and global organization of synaptic inputs on cortical dendrites

Synaptic inputs on cortical dendrites are organized with remarkable subcellular precision at the micron level. This organization emerges during early postnatal development through patterned spontaneous activity and manifests both locally where synapses with similar functional properties are clustered, and globally along the axis from dendrite to soma. Recent experiments reveal species-specific differences in the local and global synaptic organization in mouse, ferret and macaque visual cortex. I will present a computational framework that implements functional and structural plasticity from spontaneous activity patterns to generate these different types of organization across species and scales. Within this framework, a single anatomical factor - the size of the visual cortex and the resulting magnification of visual space - can explain the observed differences. This allows us to make predictions about the organization of synapses also in other species and indicates that the proximal-distal axis of a dendrite might be central in endowing a neuron with powerful computational capabilities.

Structural Plasticity in the Monkey Entorhinal and Perirhinal Cortices Following Selective Hippocampal Lesion

Maturing neurons and dual structural plasticity enable flexibility and stability of olfactory memory

COSYNE 2023

Activity-based anorexia-induced alteration of membrane-associated glucocorticoid receptors and structural plasticity in the hippocampus of adolescent female rats

Microglia motility depends on neuronal activity and is associated with structural plasticity of dendritic spines in the hippocampus

Modeling effects of Repetitive Transcranial Magnetic Stimulation protocols in recurrent neural networks with homeostatic structural plasticity: exploring the rTMS parameter space

Multimodal analysis of structural plasticity of cortical grey matter volume in chronic pain

Structural plasticity of dendritic spines within cocaine-seeking neuronal ensembles

Structural plasticity during vision-dependent learning in mouse visual cortex

Structural plasticity with a Gaussian activity rule predicts deprivation-induced network remodeling

Activation of Ca2+-permeable AMPARs and intracellular calcium stores are required for structural plasticity induced by sTBS in the mouse hippocampus

FENS Forum 2024

Cortical inactivation of Darpp-32 impairs synaptic and structural plasticity associated with motor learning

FENS Forum 2024

Extracellular proteolytic cascade remodels the ECM to promote structural plasticity

FENS Forum 2024

The role of tenascin-C in the structural plasticity of perineuronal nets and synaptic expression in the murine hippocampus

FENS Forum 2024

VEGFD signaling balances stability and activity-dependent structural plasticity of dendrites

FENS Forum 2024