Biology subjects

Vaasjo, L. O.

Publications and source records attributed to Vaasjo, L. O..

3 recordsLinked to original sources

bioRxiv2025

Dendritic inhibition terminates plateau potentials in CA1 pyramidal neurons

In CA1 pyramidal neurons (CA1-PYRs), plateau potentials control synaptic plasticity and the emergence of place cell identity. Here, we show that dendritic inhibition terminates plateaus in an all-or-none manner. Plateaus were initially resistant to inhibition but became increasingly susceptible to termination as they progressed. Between two distinct subtypes of dendrite-targeting interneurons, OLMNdnf generated slower postsynaptic currents that terminated plateaus more effectively than OLM2. Voltage-gated Ca2+ channels (VGCCs) were necessary for plateaus, which were prolonged by blocking small-conductance Ca2+-activated K+ channels (SK). A single-compartment model with these two conductances recapitulated core experimental findings and provided a mechanistic explanation for terminations. Plateaus arose from VGCCs maintained in the active state by sustained Ca2+ influx, a positive feedback loop that was quasi-balanced by ISK. Inhibition terminated plateaus by driving the membrane potential below a dynamic threshold to deactivate VGCCs and end the positive feedback loop. Lastly, two-photon Ca2+ imaging showed that plateaus evoke large dendritic Ca2+ transients that were graded by terminations. Overall, our results demonstrate how the feedback inhibitory circuit interacts with intrinsic cellular mechanisms to regulate plateau potentials and shape dendritic Ca2+ signals in CA1-PYRs.

neuroscience↗

bioRxiv2021

A microRNA cluster downstream of the selector gene Fezf2 coordinates fate specification with dendritic branching in cortical neurons

In the cerebral cortex, cortical projection neurons comprise classes of neurons project to distant regions of the central nervous system. These neurons develop from the same progenitor pool, but they acquire strikingly different inputs and outputs to underpin strikingly different functions. The question of how corticospinal projection neurons - involved in motor function and implicated in paralysis - and callosal projection neurons - involved in cognitive function and implicated in autism - develop represents a fundamental and clinically important question in neurodevelopment. A network of transcription factors, including the selector gene Fezf2, is central to specifying cortical projection neuron fates. Gene regulation up- and down-stream of these transcription factors, however, is not well understood, particularly as it relates to the development of the major inputs to cortical projection neurons. Here we show that the miR-193b~365 microRNA cluster downstream of Fezf2 cooperatively represses the signaling molecule Mapk8, and impacts dendritic branching of cortical projection neurons.

developmental biology↗

bioRxiv2020

Nicotine exposure and neuronal activity regulate Golgi membrane dispersal and distribution

How nicotine exposure produces long-lasting changes that remodel neural circuits with addiction is unknown. Here, we report that long-term nicotine exposure alters the trafficking of 4{beta}2-type nicotinic acetylcholine receptors (4{beta}2Rs) by dispersing and redistributing the Golgi apparatus. In cultured neurons, dispersed Golgi membranes were distributed throughout somata, dendrites and axons. Small, mobile vesicles in dendrites and axons lacked standard Golgi markers and were identified by other Golgi enzymes that modify glycans. Nicotine exposure increased levels of dispersed Golgi membranes, which required 4{beta}2R expression. Similar nicotine-induced changes occurred in vivo at dopaminergic neurons at mouse nucleus accumbens terminals, consistent with these events contributing to nicotines addictive effects. Characterization in vitro demonstrated that dispersal was reversible, that dispersed Golgi membranes were functional, and that membranes were heterogenous in size, with smaller vesicles emerging from larger "ministacks", similar to Golgi dispersal induced by nocadazole. Protocols that increased cultured neuronal synaptic excitability also increased Golgi dispersal, without the requirement of 4{beta}2R expression. Our findings reveal novel activity- and nicotine-dependent changes in neuronal intracellular morphology. These changes regulate levels and location of dispersed Golgi membranes at dendrites and axons, which function in local trafficking at subdomains.

neuroscience↗