Biology subjects

Mesik, L.

Publications and source records attributed to Mesik, L..

4 recordsLinked to original sources

bioRxiv2026

Visual deprivation in adulthood engages presynaptic plasticity of thalamocortical synapses

Synaptic plasticity between neurons in first order thalamus and layer 4 cortex is greatest during an early postnatal critical period and was thought to decrease irreversibly with age. However, here we show that robust and reversible plasticity can be induced in adult mice at synapses between dLGN axons and visual cortex layer 4 neurons by prolonged dark exposure (DE) and light reintroduction (LRx). Unexpectedly, the experience-dependent change in synaptic strength was mediated by a change in presynaptic structure, organization and function. DE/LRx declusters/clusters synaptic vesicles and reorganizes presynaptic molecular geometry. Furthermore, DE/LRx decreases/increases visually-evoked and spontaneous calcium signaling and neurotransmitter release probability in dLGN axonal boutons. The presynaptic plasticity mechanism described here has a high threshold for engagement which would allow maintenance of synapse stability across a wide activity range, and reactivation of thalamocortical plasticity in extraordinary conditions.

neuroscience↗

bioRxiv2024

Adult visual deprivation engages associative, presynaptic plasticity of thalamic input to cortex

Age constrains plasticity at inputs from first order thalamic nuclei to the cortex, endowing stability to ascending, feed-forward projections. However, here we show that prolonged visual deprivation can induce robust and reversible plasticity at thalamocortical synapses in layer 4 pyramidal neurons in the adult mouse primary visual cortex. The plasticity engaged by prolonged visual deprivation is non-homeostatic and mediated by changes in presynaptic function.

neuroscience↗

bioRxiv2021

Norepinephrine Potentiates and Serotonin Depresses Visual Cortical Responses by Transforming Eligibility Traces

Reinforcement allows organisms to learn which stimuli predict subsequent biological relevance. Hebbian mechanisms of synaptic plasticity are insufficient to account for reinforced learning because neuromodulators signaling biological relevance are delayed with respect to the neural activity associated with the stimulus. A theoretical solution is the concept of eligibility traces (eTraces), silent synaptic processes elicited by activity which upon arrival of a neuromodulator are converted into a lasting change in synaptic strength. Previously we demonstrated in visual cortical slices the Hebbian induction of eTraces and their conversion into LTP and LTD by the retroactive action of norepinephrine and serotonin Here we show in vivo in V1 that the induction of eTraces and their conversion to LTP/D by norepinephrine and serotonin respectively potentiates and depresses visual responses. We also show that the integrity of this process is crucial for ocular dominance plasticity, a canonical model of experience-dependent plasticity.

neuroscience↗

bioRxiv2018

A genetically-encoded fluorescent acetylcholine indicator

Acetylcholine (ACh) regulates a diverse array of physiological processes throughout the body, yet cholinergic transmission in the majority of tissues/organs remains poorly understood due primarily to the limitations of available ACh-monitoring techniques. We developed a family of G-protein-coupled receptor activation-based ACh sensors (GACh) with sensitivity, specificity, signal-to-noise ratio, kinetics and photostability suitable for monitoring ACh signals in vitro and in vivo. GACh sensors were validated with transfection, viral and/or transgenic expression in a dozen types of neuronal and non-neuronal cells prepared from several animal species. In all preparations, GACh sensors selectively responded to exogenous and/or endogenous ACh with robust fluorescence signals that were captured by epifluorescent, confocal and/or two-photon microscopy. Moreover, analysis of endogenous ACh release revealed firing pattern-dependent release and restricted volume transmission, resolving two long-standing questions about central cholinergic transmission. Thus, GACh sensors provide a user-friendly, broadly applicable toolbox for monitoring cholinergic transmission underlying diverse biological processes.

neuroscience↗