bioRxiv Science⌕ Search

bioRxiv · 10.1101/097279

Electro-diffusion modulation of synaptic input in dendritic spines using deconvolved voltage sensor time series

Abstract

The inward current flowing inside the post-synaptic terminal of a neuron modulates transiently the membrane voltage potential. Most of the excitatory connections are made on dendritic spines characterized by a large variability in their geometry.How the voltage in a spine is modulated by geometry remains elusive due in part to the absence of direct measurements. To understand the spine voltage-current relation, we develop here a model for the voltage and we use it to extract electrical properties from live cell imaging data. We first deconvolve the genetically encoded voltage sensor expressed in hippocampal neurons and then use electro-diffusion theory, to compute the electric field and the ionic flows induced in a dendritic spine.The ionic flow is driven by the electric field coupled to the charge densities that interact through the non-cylindrical spine geometry. We determine the I-V relation and conclude that the spine effective resistance is mostly determined by the neck geometry. This modulation of synaptic inputs by the spine neck is significantly larger than what was expected from traditional cable models. Thus modulating the postsynaptic current can be achieved by changing the number of receptors or by altering the spine geometry which independently affects the transformation of current into voltage.\n\nSignificance statementDendritic spines are geometrical structures receiving most of the excitatory transmission, yet how they modulate voltage from the synaptic current is not clear due to their submicron small size and specific non-cylindrical geometry. We study here the conversion of the synaptic current into voltage modulated by the spine geometry. Our approach is based on the electro-diffusion theory and we show that the spine neck is the main resistance filter, while the voltage is maintained constant in the head. Finally, we extract the effective resistance using a deconvolution of the genetically encoded voltage indicators expressed in hippocampal neurons. The present approach allows studying the electrical properties of many other structures such as glial small protrusions, cilia, and many others.

Explore related subjects

Keep this discovery

Explore connections, maps & timelines

BibTeXRIS

Cartailler, J., Kwon, T., Yuste, R., Holcman, D.. 2016-12-29. Electro-diffusion modulation of synaptic input in dendritic spines using deconvolved voltage sensor time series. https://doi.org/10.1101/097279

Cite the original work for its findings. Save a collection to share your selection of sources.

KEEP EXPLORING

Related preprints

EigenBrain maps cortical molecular architecture from functional, geometric, and structural eigenmodes

Neurotransmitter receptor and transporter distributions shape neural communication across the cortex and underpin mechanistic interpretations of brain function. Magnetic resonance imaging (MRI)-derived eigenmodes, low-dimensional spatial patterns that capture the principal axes of cortical organization, are increasingly used to reconstruct brain maps and offer a potential route to approximating molecular topographies in large cohorts where direct measurements are unavailable. Yet whether the type of MRI data used to derive these eigenmodes determines which receptor and transporter distributions can be approximated, and which molecular systems are accessible through this approach at all, remains unknown. Using a spatial reconstruction framework applied to 23 molecular systems spanning neurotransmitter, metabolic, and pathological markers, we show that eight receptor and transporter maps, spanning serotonin, dopamine, histamine, cholinergic, and opioid markers, can be selectively approximated from functional eigenmodes but not structural or geometric ones. This selectivity also reveals that functional brain organization encodes a specific subset of neuromodulatory topographies that structural and geometric organization does not. To illustrate translational potential in clinical cohorts where molecular imaging is unavailable, we applied individual-level eigenmode decompositions of MRI data projected onto the eight validated molecular systems and detected cross-sectional differences in autism and longitudinal changes in schizophrenia. Together, these findings reveal a difference in how geometric, structural, and functional brain organization relate to molecular architecture, offering a method for approximating validated molecular profiles in population neuroimaging cohorts that lack direct molecular imaging.

neuroscience↗

Sex differences in fear extinction are conditional, not categorical

Threat memories are dynamic, and their behavioral expression can change with subsequent experience and the passage of time. Extinction training can reduce conditioned fear responses, yet these responses may re-emerge over time through spontaneous recovery. Although biological sex has been implicated as modulatory factor in fear and extinction memory processes, studies have reported inconsistent findings. Here, we investigated how differences in extinction training and the timing of memory assessment influence extinction memory in male and female mice. Using contextual fear conditioning, we assessed fear acquisition and threat retention, characterized within-session and across-session extinction during repeated training, and compared shorter (3-minute) and longer (6-minute) daily extinction sessions. We subsequently evaluated extinction memory retention and spontaneous recovery at a later time point. Estrous-cycle stage in females was monitored daily throughout the experimental protocol to examine its potential association with fear and extinction behavior. We found that males and females demonstrated comparable fear acquisition and threat memory, as well as similar extinction progression across days. During longer extinction sessions, but not shorter, males showed greater within-session reductions in freezing, whereas females exhibited modestly higher overall freezing. We found no significant sex difference in the magnitude of spontaneous recovery. There was no significant association between estrous-cycle stage and freezing behavior. Together, our findings suggest that sex-dependent differences in contextual fear extinction are not uniformly expressed, but rather depend on the experimental conditions under which extinction is assessed

neuroscience↗

LAMA2-related muscular dystrophy alters Schwann cell calcium homeostasis and increases peripheral nerve inflammation

LAMA2-related muscular dystrophy (LAMA2-RD) affects skeletal muscle and peripheral nerves, yet the consequences of LAMA2 deficiency on peripheral nerve integrity beyond early postnatal development remain incompletely understood. We investigated sciatic nerve architecture and molecular alterations across postnatal life in hypomorphic Lama2dy2J/dy2J mice. LAMA2 localizes around the abaxonal surface of myelinating Schwann cells in control nerves. LAMA2-deficient nerves exhibited patchy regions lacking myelinated axons from early postnatal stages into adulthood, including expanded Remak bundles along with axons completely lacking normal Schwann cell ensheathment. In adult nerves, myelin infolding and reduced myelin circularity revealed abnormalities in the architecture of myelin that had formed. Bulk sciatic nerve RNA sequencing identified altered calcium-signaling and immune-related transcriptional signatures. Complementary Fura Red measurements in primary nerve-derived Schwann cell cultures demonstrated decreased intracellular calcium in LAMA2-deficient samples, while ATP-evoked responses were preserved. Older LAMA2-deficient nerves also exhibited increased CD45+CD11b+ myeloid-cell infiltration. Together, these observations extend the characterization of LAMA2-associated neuropathy into adulthood and identify calcium homeostasis and neuroimmune responses as candidate processes relevant to persistent peripheral nerve pathology.

neuroscience↗