Biology subjects

Gonzalez-Islas, C. E.

Publications and source records attributed to Gonzalez-Islas, C. E..

3 recordsLinked to original sources

bioRxiv2025

Localization of Fascin to Dendritic Protrusions Regulates Postsynaptic Plasticity

The Fascin family of actin-bundling proteins is best known for organizing actin filaments (F-actin) into tightly packed bundles that drive dynamic membrane protrusions such as filopodia. In neurons, fascin has been thought to primarily function in axons, as previous studies reported its absence from dendritic filopodia and spines. Here, we demonstrate that fascin is both present and functionally important in dendritic compartments. Using optimized immunocytochemistry and CRISPR-based endogenous tagging of fascin1 in cultured hippocampal neurons, we show that fascin is concentrated in developing dendritic filopodia and enriched in mature dendritic spines. Super- resolution imaging further reveals that fascin is organized into discrete nanoscale foci within spine heads, but not the spine neck. Finally, we show that CRISPR-mediated knockout of fascin1 in mature hippocampal neurons impairs synaptic potentiation, without affecting baseline excitatory synaptic transmission. Together, our findings uncover a previously overlooked aspect of actin organization in dendritic spines and establish fascin as a critical regulator of postsynaptic plasticity. Summary StatementThe actin bundling protein fascin localizes to dendritic filopodia and spines, where it regulates activity-dependent synaptic plasticity.

neuroscience↗

bioRxiv2023

GABAergic synaptic scaling is triggered by changes in spiking activity rather than transmitter receptor activation.

Homeostatic plasticity represents a set of mechanisms that are thought to recover some aspect of neural function. One such mechanism called AMPAergic scaling was thought to be a likely candidate to homeostatically control spiking activity. However, recent findings have forced us to reconsider this idea as several studies suggest AMPAergic scaling is not directly triggered by changes in spiking. Moreover, studies examining homeostatic perturbations in vivo have suggested that GABAergic synapses may be more critical in terms of spiking homeostasis. Here we show results that GABAergic scaling can act to homeostatically control spiking levels. We found that perturbations which increased or decreased spiking in cortical cultures triggered multiplicative GABAergic upscaling and downscaling, respectively. In contrast, we found that changes in AMPAR or GABAR transmission only influence GABAergic scaling through their indirect effect on spiking. We propose that GABAergic scaling represents a stronger candidate for spike rate homeostat than AMPAergic scaling. Significance StatementThe nervous system maintains excitability in order to perform network behaviors when called upon to do so. Networks are thought to maintain spiking levels through homeostatic synaptic scaling, where compensatory multiplicative changes in synaptic strength are observed following alterations in cellular spike rate. Although we demonstrated that AMPAergic synaptic scaling does not appear meet these criteria as a spike rate homeostat, we now show that GABAergic scaling could play this role. Here we present evidence that the characteristics of GABAergic scaling place it in an excellent position to be a spiking homeostat. This work highlights the importance of inhibitory circuitry in the homeostatic control of excitability. Further, it provides a point of focus into neurodevelopmental disorders where excitability is impaired.

neuroscience↗

bioRxiv2019

Homeostatic recovery of embryonic spinal activity initiated by compensatory changes in resting membrane potential.

When baseline activity in a neuronal network is modified by external challenges, a set of mechanisms is prompted to homeostatically restore activity levels. These homeostatic mechanisms are thought to be profoundly important in the maturation of the network. We have previously shown that 2-day blockade of either excitatory GABAergic or glutamatergic transmission in the living embryo transiently blocks the movements generated by spontaneous network activity (SNA) in the spinal cord. However, by 2 hours of persistent receptor blockade embryonic movements begin to recover, and by 12 hours we observe a complete homeostatic recovery in vivo. Compensatory changes in voltage-gated conductances in motoneurons were observed by 12 hours of blockade, but not changes in synaptic strength. It was unclear whether changes in voltage-gated conductances were observed by 2 hours of blockade when the recovery actually begins. Further, compensatory changes in voltage-gated conductances were not observed following glutamatergic blockade where embryonic movements were blocked but then recovered in a similar manner to GABAergic blockade. In this study, we discover a mechanism for homeostatic recovery in these first hours of neurotransmitter receptor blockade. In the first 6 hours of GABAergic or glutamatergic blockade there was a clear depolarization of resting membrane potential in both motoneurons and interneurons. These changes reduced action potential threshold and were mainly observed in the continued presence of the antagonist. Therefore, it appears that fast changes in resting membrane potential represent a key fast homeostatic mechanism for the maintenance of network activity in the living embryonic nervous system.\n\nSignificanceHomeostatic plasticity represents a set of mechanisms that act to recover cellular or network activity following a challenge to that activity and is thought to be critical for the developmental construction of the nervous system. The chick embryo afforded us the opportunity to observe in a living developing system the timing of the homeostatic recovery of network activity following 2 distinct perturbations. Because of this advantage, we have identified a novel homeostatic mechanism that actually occurs as the network recovers and is therefore likely to contribute to nervous system homeostasis. We found that a depolarization of the resting membrane potential in the first hour of the perturbations enhances excitability and supports the recovery of embryonic spinal network activity.

neuroscience↗