Biology subjects

Bridi, M.

Publications and source records attributed to Bridi, M..

4 recordsLinked to original sources

bioRxiv2022

GluN2B-containing NMDA receptors are required for potentiation and depression of responses in ocular dominance plasticity

Monocular deprivation (MD) causes an initial decrease in synaptic responses to the deprived eye in juvenile mouse primary visual cortex (V1) through Hebbian long-term depression (LTD). This is followed by a homeostatic increase, which has been attributed to synaptic scaling. However, homeostasis during other forms of visual deprivation is caused by sliding the threshold for Hebbian long-term potentiation (LTP) rather than scaling. We therefore asked whether the homeostatic increase during MD requires GluN2B-containing NMDA receptor activity, which is required to slide the plasticity threshold but not for synaptic scaling. Selective GluN2B blockade from 2-6d after monocular lid suture prevented the homeostatic increase in miniature excitatory postsynaptic current (mEPSC) amplitude in monocular V1 of acute slices and prevented the increase in visually evoked responses in binocular V1 in vivo. The decrease in mEPSC amplitude and visually evoked responses during the first 2d of MD also required GluN2B activity. Together, these results indicate that GluN2B-containing NMDA receptors first play a role in LTD immediately following eye closure, and then promote homeostasis during prolonged MD by sliding the plasticity threshold in favor of LTP.

neuroscience↗

bioRxiv2021

Daily oscillation of the excitation/inhibition ratio is disrupted in two mouse models of autism

Alterations to the balance between excitation and inhibition (E/I ratio) are postulated to underlie behavioral phenotypes in autism spectrum disorder (ASD) patients and mouse models. However, in wild type mice the E/I ratio is not constant, but instead oscillates across the 24h day. Therefore, we tested whether the E/I oscillation, rather than the overall E/I ratio, is disrupted in two ASD-related mouse lines: Fmr1 KO and BTBR, models of syndromic and idiopathic ASD, respectively. The E/I ratio is dysregulated in both models, but in different ways: the oscillation is lost in Fmr1 KO and reversed in BTBR mice. In both models these phenotypes associate with differences the timing of excitatory and inhibitory synaptic transmission and endocannabinoid signaling compared to wild type mice, but not with altered sleep. These findings raise the possibility that ASD-related phenotypes may be produced by a mismatch of E/I to the appropriate behavioral state, rather than alterations to overall E/I levels per se.

neuroscience↗

bioRxiv2019

Reduced Cognitive Performance in Aged Rats Correlates with Increased Excitation/Inhibition Ratio in the Dentate Gyrus in Response to Lateral Entorhinal Input

Aging often impairs cognitive functions associated with the medial temporal lobe (MTL). Anatomical studies identified the layer II pyramidal cells of the lateral entorhinal cortex (LEC) as one of the most vulnerable elements within the MTL. These cells provide a major excitatory input to the dentate gyrus hippocampal subfield by synapsing onto granule cells and onto local inhibitory interneurons, and a fraction of these contacts are lost in aged individuals with impaired learning. Using optogenetics we evaluated the functional status of the remaining inputs in an outbred rat model of aging that distinguishes between learning impaired and learning unimpaired individuals. We found that aging affects the pre- and postsynaptic strength of the LEC inputs onto granule cells. However, the magnitude these changes was similar in impaired and un-impaired rats. In contrast, the recruitment of inhibition by LEC activation was selectively reduced in the aged impaired subjects. These findings are consistent with the notion that the preservation of an adequate balance of excitation and inhibition is crucial for maintain proficient memory performance during aging.

neuroscience↗

bioRxiv2018

Dynamic recovery from depression enables rate encoding in inhibitory synapses

Fast-spiking parvalbumin positive interneurons (PV-INs) are essential for controlling network firing and the gain of the cortical response to sensory stimulation. Crucial for these functions, PV-INs can sustain high frequency firing with no accommodation. However, PV-INs also exhibit short-term depression (STD) during sustained activation, which is largely due to the depletion of synaptic resources (vesicles). In most synapses the rate of replenishment of depleted vesicles is constant, determining an inverse relationship between the STD level and the activation rate, which theoretically, severely limits rate coding capabilities. We examined STD of the PV-IN to pyramidal cell synapse in the mouse visual cortex, and found that in these synapses the recovery of depleted resources is not constant but increases linearly with the frequency of use. By combining modeling, dynamic clamp and optogenetics, we demonstrated that this dynamic regulation of recovery enables PV-INs to reduce pyramidal cell firing in a linear manner, which, theoretically, is crucial for controlling the gain of cortical visual responses.

neuroscience↗