Biology subjects

Attardo, A.

Publications and source records attributed to Attardo, A..

6 recordsLinked to original sources

bioRxiv2026

Mapping and longitudinal imaging of potentiated synapses in the mouse hippocampus using SynActive-eGRASP

Identifying individual synapses that undergo long-term potentiation following learning at specific circuits remains a major challenge in neuroscience. To address this problem, we developed SA-eGRASP, a genetically encoded reporter that combines SynActive (SA) targeting with enhanced GFP Reconstitution Across Synaptic Partners (eGRASP). SA drives the expression of the postsynaptic half of eGRASP at potentiated spines via the 5' and 3' untranslated regions (UTRs) of the immediate-early gene Arc, thus enabling selective labeling of individual synapses that are both structurally connected and have undergone potentiation through transsynaptic GFP reconstitution. Here, we validated SA-eGRASP and combined it with high-resolution optical imaging to generate a detailed map of hippocampal CA3-CA1 synapses subjected to potentiation following contextual fear conditioning in mice. The high signal-to-noise ratio of SA-eGRASP, allowed us to track individual potentiated dendritic spines over the course of several days, to investigate the long-term dynamics of CA3-CA1 potentiated dendritic spines, and to study the selective potentiation of a subset of spines upon experience. SA-eGRASP paves the way to the investigation of synaptic engrams by enabling longitudinal, circuit-specific investigation of synapses potentiated during learning in mice performing naturalistic behaviors.

neuroscience↗

bioRxiv2026

Comparison of place field detection methods and their effect on place field stability and drift in mouse dCA1.

BackgroundHippocampal place cells (PCs) undergo representational drift, i.e., a gradual change in their place fields despite unaltered behavior. While Ca2+ imaging enables long-term tracking of PC populations, distinct PC detection methods have been shown to yield different subpopulations of PCs, with only a few systematic comparisons between methods, especially in open arenas. New MethodWe provide an analysis protocol for one-photon PC data obtained during free foraging in two-dimensional arenas that allows us to compare two widely used PC detection methods, significance of spatial information (SI), and split-half correlation (SHC), and their effect on representational drift. The analysis is demonstrated on previously published Ca2+ data from dorsal CA1 of freely foraging mice, with cells tracked for 10 consecutive days. ResultsBoth criteria, SI and SHC, yielded proportions of approx. 17% PCs with only 40% overlap. SI-identified PCs demonstrated higher stability, higher rate map correlations, and a slower rate of representational drift than SHC-PCs. Comparison with existing methodsPrevious studies comparing SI and SHC PC detection methods in Ca2+ data did not focus on either open field behavior or representational drift. ConclusionOur results indicate that the choice of PC detection method significantly affects the estimate of representational drift in Ca2+ imaging studies.

neuroscience↗

bioRxiv2025

Learning reorganizes dendritic and stabilizes axonal initial segment inhibitory synapses in CA1 pyramidal neurons

Structural synaptic plasticity underlies the changes in brain connectivity required for learning and memory. Inhibitory synapses (INS) target all subcellular domains of excitatory pyramidal neurons (PNs), including dendrites, somata and axon initial segments (AIS). These subcellular domains have distinct molecular, structural and physiological profiles which underlie their functions. How structural plasticity of INS supports these functions as well as emerging properties such as memory is largely unknown. To tackle these questions we tracked INS on dendrites, somata and AIS of PNs in the dorsal hippocampal CA1 area of mice over two weeks. Size and temporal dynamics of INS showed a strong compartmentalization and dendritic INS were less dynamic than dendritic spines. Trace fear conditioning led to reorganization of dendritic INS and to stabilization of AIS INS but had a minimal effect on dendritic spines. Finally, mathematical modelling allowed us to probe the mechanisms underlying stabilization of INS upon learning.

neuroscience↗

bioRxiv2025

Neuropeptide CRH prevents premature differentiation of OPCs following CNS injury and in early postnatal development

The role of neuropeptides and their receptors in oligodendrocyte progenitor cells (OPCs) has largely been overlooked so far. Here, we describe a new subpopulation of corticotropin-releasing hormone (CRH)-expressing OPCs that aggregate around acute brain injuries and exhibit an elevated capacity to differentiate into myelinating oligodendrocytes (OLs). We found that CRH expression in OPCs is rapidly induced de novo as a transient response within the first 72 hours after injury. As target cells, we identified CRH receptor type 1 (CRHR1)-expressing OPCs which show a decreased differentiation velocity. We demonstrate that CRH/CRHR1 system inactivation increases the speed of OL generation compromising the long-term survival of OLs after acute injury. Furthermore, we prove that a CRH/CRHR1 system deficiency under non-injury conditions leads to increased early postnatal oligodendrogenesis and alterations in adult myelination. Altogether, we show that OPC-derived CRH not only actively influences the injury environment through the interaction with CRHR1-expressing OPCs, but also identify the G-protein coupled receptor CRHR1 as a critical modulator of oligodendrogenesis at early postnatal stages with lasting effects on adult myelination.

neuroscience↗

bioRxiv2020

Aberrant structural synaptic dynamics precede disorganization of temporal and spatial coding in the hippocampus upon repeated stress exposure

Stress exposure strongly contributes to the pathophysiology of psychiatric diseases such as depression, schizophrenia, anxiety, and post-traumatic stress disorder. It also affects both function and structure of hippocampal CA1, leading to episodic memory impairment. Here, we used deep-brain optical imaging to elucidate the effects of stress on CA1 pyramidal neuron structural connectivity and activity. We tracked dynamics of dendritic spines during repeated stress and found decrease in spinogenesis followed by decrease in spine stability. In contrast to repeated stress, acute stress led to stabilization of the spines born in temporal proximity to the stressful event. To investigate the link between structural plasticity and activity patterns upon repeated stress, we studied the activity of thousands of CA1 pyramidal neurons in freely-moving. We found an increase in activity and loss of temporal organization followed by a disruption in temporal and spatial coding. Our data suggest that stress-induced sustained increase in activity leads to loss of structural connectivity and subsequent temporal and spatial coding impairments.

neuroscience↗

bioRxiv2019

Stability of excitatory structural connectivity predicts the probability of CA1 pyramidal neurons to become engram neurons

Neurons undergoing activity-dependent plasticity represent experience and are functional for learning and recall thus they are considered cellular engrams of memory. Although increase in excitability and stability of structural synaptic connectivity have been implicated in the formation and persistance of engrams, the mechanisms bringing engrams into existence are still largely unknown. To investigate this issue, we tracked the dynamics of structural excitatory synaptic connectivity of hippocampal CA1 pyramidal neurons over two weeks using deep-brain two-photon imaging in live mice. We found that neurons that will prospectively become part of an engram display higher stability of connectivity than neurons that will not. A novel experience significantly stabilizes the connectivity of non-engram neurons. Finally, the density and survival of dendritic spines negatively correlates to freezing to the context but not to the tone in a trace fear conditioning learning paradigm.

neuroscience↗