Dendritic spines

…noise, and the 3D structure of dendritic spines. In this talk I will describe one such project testing if wiring motifs from fly brain connectomes can improve performance of reservoir computers, a type of recurrent neural network

…their fast, brief incorporation in dendritic spines after LTP induction but offer limited insights into long-lasting changes in AMPAR content at potentiated spines[1,2]. Hence, a unified modeling framework is necessary to understand persistent synaptic changes in AMPAR numbers. Molecular trafficking, such as diffusion, active transport, endo/exocytos

…actively modulate the formation of new dendritic spines.To examine this relationship, we target microglia-synapse communicatio

The major neuropathologic feature of Parkinson’s disease is the presence of widespread intracellular inclusions of α-synuclein known as Lewy bodies. Evidence suggests that these misfolded protein inclusions spread through the brain with disease progression. Changes in synaptic function precede neurodegeneration, and this extracellular α-synuclein can affect synaptic transmission. However, whether and how the spreading of α-synuclein aggregates modulates synaptic function before neuronal loss remains unknown. In the present study, we investigated the effect of intrastriatal injection of α-synuc

…of both long-term potentiation and dendritic spines’ structure. At behavioral level, RNF10 downregulation suppres

Developmental myelination is a protracted process in the mammalian brain. One theory for why oligodendrocytes mature so slowly posits that myelination may stabilize neuronal circuits and temper neuronal plasticity as animals age. We tested this theory in the visual cortex, which has a well-defined critical period for experience-dependent neuronal plasticity. During adolescence, visual experience modulated oligodendrocyte maturation in visual cortex. To determine whether oligodendrocyte maturation in turn regulates neuronal plasticity, we genetically blocked oligodendrocyte differentiation and

Ventral pathway circuits are constituted by the interconnected brain areas that are distributed throughout the brain. They are primarily involved in processing of object related information in brain. However, their role in object recognition memory (ORM) enhancement remains unknown. In this study, we show that an activation of each of the brain areas interconnected to ventral pathway circuits individually induced enhancement in ORM; however, same treatment in brain areas not interconnected to ventral pathway circuits produced no effect. Further study in perirhinal cortex (PRh), area V2 of visu

The cerebellum is a multifunctional brain region, controlling various motor and non-motor behaviors. Alterations in its architecture/function contribute to neurodevelopmental disorders, including autism spectrum disorders. In Niemann-Pick C1 (NPC1) disease, a lysosomal lipid accumulation disorder, cerebellar granule cells (GCs) proliferation and migration are impaired, due to reduced levels of Shh and BDNF during early postnatal development, affecting cerebellar cytoarchitecture.Since GCs complete their differentiation in early postnatal life driven by BDNF signaling, establishing synaptic con

Dendritic spines of pyramidal neurons are thin protrusions of the neuron membrane and represent the main postsynaptic sites in the cerebral cortex. Spines can have different morphologies: investigating their shape gives indications about the functional state of synapses during brain development. Quantifying dendritic spine shape changes will boost the comprehension of several neuropathies, such as Alzheimer and autism spectrum. Detection of dendritic spines is challenged by optical limitations. We propose a fully automated pipeline to segment and cluster spines to classify them according to th

…synaptic transmission and improper dendritic spines morphogenesis, which are tough to underlies the bulk of the cognitive and behavioral defects exhibited by FXS patients. However, our current understanding of FXS physiopathology

Aim: Motor learning significantly impacts daily life, triggering notable changes in the primary motor cortex (M1) and basal ganglia (BG). Dopamine (DA) mediates these changes, with Darpp-32 playing a key role in DA transmission. Although extensively studied in the BG's striatum, Darpp-32's function in the motor cortex remains largely unexplored. This study aims to characterize Darpp-32 in motor cortices, examining cellular expression and its impact on motor behavior, synaptic and structural plasticity.Methods: Anatomical study: Using C57BL/6 mice, we examined Darpp-32 distribution across corti

Dendritic spines are the seat of most excitatory synapses in the brain, and a cellular structure considered central to learning, memory, and activity-dependent plasticity. Typically, humans quantify dendritic spines from light microscopy data in a manual painstaking, error-prone process. We found that human-to-human variability is substantial (inter-rater reliability 82.2±6.4 %), raising concerns about the reproducibility of experiments and the validity of using human-annotated 'ground truth' as an evaluation method for computational approaches of spine identification. To address this, we pres

Brain tissue comprises an extremely complex arrangement of cells that together make up the information- processing network enabling brain function. The connectivity of neurons underlies the unparalleled capabilities of our mind. Thus, mapping brain structure, which underlies brain function, has become a central focus in neuroscience.Electron microscopy provides extremely high resolution and comprehensive visualization of brain structure but requires correlative workflows to access molecular information. Light microscopy holds tremendous potential to analyze the ultrastructure of brain tissue t

Alzheimer’s disease (AD) is the most common cause of dementia. Until now, none of the approved AD treatments turned out to be a success. AD is unknown but involves genetic, biochemical, and environmental factors. Thus, one of the reasons why single-target-directed drugs have failed to reach clinical trials is the pathological complexity found in AD. It could be better contrasted by the development of Multiple Targeting Directed Ligands (MTDLs), which can modulate simultaneously multiple targets involved in the onset of the pathology. As a new strategy in drug discovery for AD, compared to comb

…which is usually located at the tip of dendritic spines. The PSD has been shown to undergo morphological changes in response to behavioral and electrophysiological inputs. This process can be highly dynamic and occurs over different time scales. To bridge the observation gap between short-term plastic events (ranging from minutes to hours) and long-term effects (several hours to days), we engineered a novel on stage microscope-incubator optimized for long-term culturing

Monosodium glutamate (MSG) is a frequently employed artificial sweetener found in numerous food products. Studies have demonstrated that when MSG is administered, it can result in glutamate toxicity and the development of epilepsy in animals. The aim of the study is to examine the effect of orally administering MSG on hippocampal dendrite morphology in Wistar and genetic absence epileptic (GAERS) rats. The rats were divided into four groups: the Wistar control group, orally administered with NaCl (1.0 g/L NaCl) for 1 month (n=5), the GAERS control group, orally administered with NaCl (1.0 g/L

…stabilization, and remodeling of dendritic spines. This protein is also implicated in plasticity phenomena, such as LTP, LTD, learning, and memory, due to its direct interaction with the GLUN2A subunit of NMDAR. The p140cap protein is encoded by the SRCIN1

Learning and memory formation require activity-dependent rearrangements of neuronal networks driven by structural plasticity. The brain's perineuronal extracellular matrix (ECM), composed mainly of chondroitin sulfate proteoglycans from the lectican family, suppresses structural plasticity in the mature brain. Several members of this family, such as aggrecan and brevican, undergo proteolytic cleavage by proteases from the ADAMTS family, which may loosen the ECM structure. Therefore, we hypothesize that activity-dependent extracellular proteolysis weakens the ECM, supporting neuronal plasticity

…Local mRNA translation is crucial for dendritic spine development and plasticity. Nonetheless, whether different mRNAs are distributed in a specific manner near synapses and how is their localization regulated after synaptic stimulation are not well-characterized. Consistent with previou

There is strong evidence that alterations in the structural and functional properties of synaptic connections during learning are underlying the formation of long-term memories. However, what specific changes in the architecture of the neuronal network are mediated by learning-induced plasticity is still poorly understood. A major limiting factor of current in vivo imaging studies of synaptic dynamics is that typically only at a small number of synapses are assessed in a given animal, typically tens to hundreds. Here, we started to apply longitudinal in vivo two-photon imaging of more than a m

…Dendritic spines, where excitatory synapses are located, represent the basic structural and functional unit of learning and memory at the neuronal level; spines are formed and/or modified during learning to support behavioral demands. However, how the interplay between plasticity and stability in dendritic spines is implemented to accommodate adaptations in behavior remains unclear. We investigated this question in head-fixed mice performing a rule-switch beh

…to dendrites, but their function in dendritic transport of neurons in vivo remains undefined. Using in vivo two-photon longitudinal imaging, we found that mice with conditional knockout of kif5b (KIF5B cKO) in CaMKIIα-Cre expressing neurons showed heightened turnover and lower stability of dendritic spines in L2/3 pyramidal neurons in the frontal association cortex. The increase of dendritic spine instability was accompanied with less postsynaptic density 95 (PSD95) acquisition in dendritic

…Leptin increases mushroom spines and the frequency of mini excitatory postsynaptic currents (mEPSCs) in developing hippocampal neurons, evidencing increased functional glutamatergic synapses. Given the presu

…transmission and elimination of dendritic spines. Interestingly, not all spines respond or undergo plasticity equally in response to mGluR-LTD. A subset of mature and more stable dendritic spines containing synaptopodin (SP), an actin-associated protein involved in local protein synthesis and calcium d