Biology subjects

Quinlan, E. M.

Publications and source records attributed to Quinlan, E. M..

7 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

All-or-none disconnection of pyramidal inputs onto parvalbumin-positive interneurons gates ocular dominance plasticity

Disinhibition is an obligatory initial step in the remodeling of cortical circuits by sensory experience. Our investigation on disinhibitory mechanisms in the classical model of ocular dominance plasticity uncovered an unexpected novel form of experience-dependent circuit plasticity. In layer 2/3 of mouse visual cortex monocular deprivation triggers a complete, "all-or-none", elimination of connections from pyramidal cells onto nearby parvalbumin-positive interneurons (PyrPV). This circuit plasticity is unique as it is transient, local and discrete. It lasts only one day, and it does not manifest as widespread changes in synaptic strength, rather, only about half of local connections are lost and the remaining ones are not affected in strength. Mechanistically, the deprivation-induced loss of PyrPV is contingent on a reduction of the protein neuropentraxin2 (NPTX2). Functionally, the loss of PyrPV is absolutely necessary for ODP. We surmise, therefore, that this "all-or-none" loss of local PyrPV circuitry gates experience-dependent cortical plasticity.

neuroscience↗

bioRxiv2020

High frequency visual stimulation primes gamma oscillations for visually-evoked phase reset and enhances spatial acuity

The temporal frequency of sensory stimulation is a decisive factor in the bidirectional plasticity of perceptual detection thresholds. However, surprisingly little is known about how distinct temporal parameters of sensory input differentially impact neuronal, circuit, and perceptual function. Here we demonstrate that brief repetitive visual stimulation is sufficient to induce long-term plasticity of visual responses, with the temporal frequency of the visual stimulus determining the location and generalization of visual response plasticity. Brief repetitive low frequency stimulation (LFS, 2 Hz) is sufficient to induce a visual response potentiation that is exclusively expressed in layer 4 in response to the familiar stimulus. In contrast, brief, repetitive high frequency stimulation (HFS, 20 Hz) suppresses the activity of fast-spiking interneurons and primes ongoing gamma oscillatory rhythms for visually-evoked phase reset. Accordingly, visual stimulation subsequent to HFS induces non-stimulus specific visual response plasticity that is expressed in all cortical layers. The generalized visual response enhancement induced by HFS is paralleled by an increase in visual acuity measured by improved performance in a visual detection task.

neuroscience↗

bioRxiv2019

Homeostatic regulation of perisynaptic MMP9 activity in the amblyopic visual cortex

Dark exposure (DE) followed by light reintroduction (LRx) reactivates robust synaptic plasticity in adult mouse V1, which allows recovery from amblyopia. Previously we showed that LRx-induced perisynaptic proteolysis of extracellular substrates by MMP9 mediates the enhanced plasticity in binocular adult mice (Murase et al., 2017). However, it is unknown if a visual system compromised by amblyopia could engage this pathway. Here we show that LRx to adult amblyopic mice induces perisynaptic MMP2/9 activity and degradation of ECM in the deprived and non-deprived V1. LRx restricted to the amblyopic eye induces equally robust MMP2/9 activity at thalamo-cortical synapses and ECM degradation in deprived V1. Two-photon live imaging demonstrates that the history of visual experience regulates MMP2/9 activity in V1, and that DE lowers the threshold for the proteinase activation. This homeostatic reduction of MMP2/9 activation threshold by DE enables the visual input from the amblyopic pathway to trigger robust perisynaptic proteolysis.

neuroscience↗

bioRxiv2019

Regulation of expression site and generalizability of experience-dependent plasticity in visual cortex

The experience-dependent decrease in stimulus detection thresholds that underly perceptual learning can be induced by repetitive exposure to a visual stimulus. Robust stimulus-selective potentiation of visual responses is induced in the primary mouse visual cortex by repetitive low frequency visual stimulation (LFVS). How the parameters of the repetitive visual stimulus impact the site and specificity of this experience-dependent plasticity is currently a subject of debate. Here we demonstrate that the stimulus selective response potentiation induced by repetitive low frequency (1 Hz) stimulation, which is typically limited to layer 4, shifts to superficial layers following manipulations that enhance plasticity in primary visual cortex. In contrast, repetitive high frequency (10 Hz) visual stimulation induces response potentiation that is expressed in layers 4 and 5/6, and generalizes to novel visual stimuli. Repetitive visual stimulation also induces changes in the magnitude and distribution of oscillatory activity in primary visual cortex, however changes in oscillatory power do not predict the locus or specificity of response potentiation. Instead we find that robust response potentiation is induced by visual stimulation that resets the phase of ongoing gamma oscillations. Furthermore, high frequency, but not low frequency, repetitive visual stimulation entrains oscillatory rhythms with enhanced sensitivity to phase reset, such that familiar and novel visual stimuli induce similar visual response potentiation.

neuroscience↗

bioRxiv2019

17α Estradiol promotes plasticity of spared inputs in the adult amblyopic visual cortex

The promotion of structural and functional plasticity by estrogens is a promising therapy to enhance central nervous system function in the aged. However, how the sensitivity to estrogens is regulated across brain regions, age and experience is poorly understood. To ask if estradiol treatment impacts structural and functional plasticity in sensory cortices, we examined the acute effect of 17 Estradiol in adult Long Evans (LE) rats following chronic monocular deprivation, a manipulation that reduces the strength and selectivity of deprived eye vision. Chronic monocular deprivation decreased thalamic input from the deprived eye to the binocular visual cortex and accelerated short-term depression of the deprived eye pathway, without changing the total density of excitatory synapses. Importantly, we found that the classical estrogen receptors ER and ER{beta} are robustly expressed in the adult visual cortex, and that a single dose of 17 Estradiol increased the size of excitatory postsynaptic densities, reduced the expression of parvalbumin and decreased the integrity of the extracellular matrix. Furthermore, 17 Estradiol enhanced experience-dependent plasticity in the amblyopic visual cortex, and promoted response potentiation of the pathway served by the non-deprived eye. The promotion of plasticity at synapses serving the non-deprived eye may reflect selectivity for synapses with an initially low probability of neurotransmitter release, and may inform applications to remap spared inputs around a scotoma or a cortical infarct

neuroscience↗