scholarly journals Regulation of perineuronal nets in the adult cortex by the electrical activity of parvalbumin interneurons

2019 ◽  
Author(s):  
Gabrielle Devienne ◽  
Sandrine Picaud ◽  
Ivan Cohen ◽  
Juliette Piquet ◽  
Ludovic Tricoire ◽  
...  
Keyword(s):  
Adult Mouse ◽  
High Plasticity ◽  
Critical Periods ◽  
Cortical Circuits ◽  
Perineuronal Net ◽  
Parvalbumin Interneurons ◽  
Mouse Visual Cortex ◽  
Activity Dependent ◽  
Dependent Mechanism

ABSTRACTPerineuronal net (PNN) accumulation around parvalbumin-expressing (PV) inhibitory interneurons marks the closure of critical periods of high plasticity, whereas PNN removal reinstates juvenile plasticity in the adult cortex. Using targeted chemogenetic in vivo approaches in the adult mouse visual cortex, we found that transient electrical silencing of PV interneurons, directly or through inhibition of local excitatory neurons, induced PNN regression. Conversely, excitation of either neuron types did not reduce the PNN. We also observed that chemogenetically inhibited PV interneurons exhibited reduced PNN compared to their untransduced neighbors, and confirmed that single PV interneurons express multiple genes enabling cell-autonomous control of their own PNN density. Our results indicate that PNNs are dynamically regulated in the adult by PV neurons acting as sensors of their local microcircuit activities. PNN regulation provides individual PV neurons with an activity-dependent mechanism to control the local remodeling of adult cortical circuits.

scholarly journals Arc restores juvenile plasticity in adult mouse visual cortex

2017 ◽  
Author(s):  
Kyle R. Jenks ◽  
Taekeun Kim ◽  
Elissa D. Pastuzyn ◽  
Hiroyuki Okuno ◽  
Andrew V. Taibi ◽  
...  
Keyword(s):  
Visual Cortex ◽  
Neural Plasticity ◽  
Critical Period ◽  
Adult Mouse ◽  
Monocular Deprivation ◽  
Protein Synthesis Inhibitor ◽  
Adult Mice ◽  
Mouse Visual Cortex ◽  
Activity Dependent

AbstractThe molecular basis for the decline in experience-dependent neural plasticity over age remains poorly understood. In visual cortex, the robust plasticity induced in juvenile mice by brief monocular deprivation (MD) during the critical period is abrogated by genetic deletion of Arc, an activity-dependent regulator of excitatory synaptic modification. Here we report that augmenting Arc expression in adult mice prolongs juvenile-like plasticity in visual cortex, as assessed by recordings of ocular dominance (OD) plasticity in vivo. A distinguishing characteristic of juvenile OD plasticity is the weakening of deprived-eye responses, believed to be accounted for by the mechanisms of homosynaptic long-term depression (LTD). Accordingly, we also found increased LTD in visual cortex of adult mice with augmented Arc expression, and impaired LTD in visual cortex of juvenile mice that lack Arc or have been treated in vivo with a protein synthesis inhibitor. Further, we found that although activity-dependent expression of Arc mRNA does not change with age, expression of Arc protein is maximal during the critical period and declines in adulthood. Finally, we show that acute augmentation of Arc expression in wild type adult mouse visual cortex is sufficient to restore juvenile-like plasticity. Together, our findings suggest a unifying molecular explanation for the age- and activity-dependent modulation of synaptic sensitivity to deprivation.Significance StatementNeuronal plasticity peaks early in life during critical periods and normally declines with age, but the molecular changes that underlie this decline are not fully understood. Using the mouse visual cortex as a model, we found that activity-dependent expression of the neuronal protein Arc peaks early in life, and that loss of activity-dependent Arc expression parallels loss of synaptic plasticity in the visual cortex. Genetic overexpression of Arc prolongs the critical period of visual cortex plasticity and acute viral expression of Arc in adult mice can restore juvenile-like plasticity. These findings provide a mechanism for the loss of excitatory plasticity with age, and suggest that Arc may be an exciting therapeutic target for modulation of the malleability of neuronal circuits.

scholarly journals Arc restores juvenile plasticity in adult mouse visual cortex

2017 ◽  
Vol 114 (34) ◽  
pp. 9182-9187 ◽  
Author(s):  
Kyle R. Jenks ◽  
Taekeun Kim ◽  
Elissa D. Pastuzyn ◽  
Hiroyuki Okuno ◽  
Andrew V. Taibi ◽  
...  
Keyword(s):  
Visual Cortex ◽  
Neural Plasticity ◽  
Critical Period ◽  
Adult Mouse ◽  
Monocular Deprivation ◽  
Protein Synthesis Inhibitor ◽  
Adult Mice ◽  
Mouse Visual Cortex ◽  
Activity Dependent

The molecular basis for the decline in experience-dependent neural plasticity over age remains poorly understood. In visual cortex, the robust plasticity induced in juvenile mice by brief monocular deprivation during the critical period is abrogated by genetic deletion of Arc, an activity-dependent regulator of excitatory synaptic modification. Here, we report that augmenting Arc expression in adult mice prolongs juvenile-like plasticity in visual cortex, as assessed by recordings of ocular dominance (OD) plasticity in vivo. A distinguishing characteristic of juvenile OD plasticity is the weakening of deprived-eye responses, believed to be accounted for by the mechanisms of homosynaptic long-term depression (LTD). Accordingly, we also found increased LTD in visual cortex of adult mice with augmented Arc expression and impaired LTD in visual cortex of juvenile mice that lack Arc or have been treated in vivo with a protein synthesis inhibitor. Further, we found that although activity-dependent expression of Arc mRNA does not change with age, expression of Arc protein is maximal during the critical period and declines in adulthood. Finally, we show that acute augmentation of Arc expression in wild-type adult mouse visual cortex is sufficient to restore juvenile-like plasticity. Together, our findings suggest a unifying molecular explanation for the age- and activity-dependent modulation of synaptic sensitivity to deprivation.

scholarly journals Activity-Dependent Modulation of Synapse-Regulating Genes in Astrocytes

2020 ◽  
Author(s):  
I Farhy-Tselnicker ◽  
MM Boisvert ◽  
H Liu ◽  
C Dowling ◽  
GA Erikson ◽  
...  
Keyword(s):  
Calcium Release ◽  
Glutamate Release ◽  
Cortical Circuits ◽  
Temporal Expression ◽  
Synaptic Development ◽  
Neuronal Synapses ◽  
Single Nucleus ◽  
And Function ◽  
Mouse Visual Cortex ◽  
Activity Dependent

SummaryAstrocytes regulate the formation and function of neuronal synapses via multiple signals, however, what controls regional and temporal expression of these signals during development is unknown. We determined the expression profile of astrocyte synapse-regulating genes in the developing mouse visual cortex, identifying astrocyte signals that show differential temporal and layer-enriched expression. These patterns are not intrinsic to astrocytes, but regulated by visually-evoked neuronal activity, as they are absent in mice lacking glutamate release from thalamocortical terminals. Consequently, synapses remain immature. Expression of synapse-regulating genes and synaptic development are also altered when astrocyte signaling is blunted by diminishing calcium release from astrocyte stores. Single nucleus RNA sequencing identified groups of astrocytic genes regulated by neuronal and astrocyte activity, and a cassette of genes that show layer-specific enrichment. Thus, the development of cortical circuits requires coordinated signaling between astrocytes and neurons, identifying astrocytes as a target to manipulate in neurodevelopmental disorders.

scholarly journals The Perils of Navigating Activity-Dependent Alternative Splicing of Neurexins

2021 ◽  
Vol 14 ◽  
Author(s):  
Kif Liakath-Ali ◽  
Thomas C. Südhof
Keyword(s):  
Synaptic Plasticity ◽  
Alternative Splicing ◽  
Synaptic Function ◽  
Plasticity Mechanism ◽  
Alternatively Spliced ◽  
Apparent Shift ◽  
Activity Dependent ◽  
Dependent Mechanism ◽  
Synaptic Responses

Neurexins are presynaptic cell-adhesion molecules essential for synaptic function that are expressed in thousands of alternatively spliced isoforms. Recent studies suggested that alternative splicing at splice site 4 (SS4) of Nrxn1 is tightly regulated by an activity-dependent mechanism. Given that Nrxn1 alternative splicing at SS4 controls NMDA-receptor-mediated synaptic responses, activity-dependent SS4 alternative splicing would suggest a new synaptic plasticity mechanism. However, conflicting results confound the assessment of neurexin alternative splicing, prompting us to re-evaluate this issue. We find that in cortical cultures, membrane depolarization by elevated extracellular K+-concentrations produced an apparent shift in Nrxn1-SS4 alternative splicing by inducing neuronal but not astroglial cell death, resulting in persistent astroglial Nrxn1-SS4+ expression and decreased neuronal Nrxn1-SS4– expression. in vivo, systemic kainate-induced activation of neurons in the hippocampus produced no changes in Nrxn1-SS4 alternative splicing. Moreover, focal kainate injections into the mouse cerebellum induced small changes in Nrxn1-SS4 alternative splicing that, however, were associated with large decreases in Nrxn1 expression and widespread DNA damage. Our results suggest that although Nrxn1-SS4 alternative splicing may represent a mechanism of activity-dependent synaptic plasticity, common procedures for testing this hypothesis are prone to artifacts, and more sophisticated approaches will be necessary to test this important question.

scholarly journals Developmental stage-specific patterned activity contributes to callosal axon projections

2021 ◽  
Author(s):  
Yuta Tezuka ◽  
Kenta M Hagihara ◽  
Kenichi Ohki ◽  
Tomoo Hirano ◽  
Yoshiaki Tagawa
Keyword(s):  
Developmental Stage ◽  
Long Range ◽  
Distinct Pattern ◽  
Network Activity ◽  
Genetic Method ◽  
Axonal Projections ◽  
Developing Neocortex ◽  
Mouse Visual Cortex ◽  
Activity Dependent

The developing neocortex exhibits patterned spontaneous network activity with various synchrony levels. However, the role of such activity in the formation of cortical circuits remains unclear. We previously reported that the development of callosal axon projections, one of the major long-range axonal projections in the brain, is activity dependent. Here, using a genetic method to manipulate network activity in a stage-specific manner, we demonstrated that spontaneous cortical network activity contributes to the region- and lamina-specific projections of callosal axons in the mouse visual cortex and that this process has a critical period: restoring neuronal activity during that period resumed the projections, whereas restoration after the period failed. Furthermore, in vivo imaging revealed that less correlated network activity was critical. Together, our findings suggest that a distinct pattern of spontaneous network activity in a specific developmental stage underlies the formation of long-range axonal projections in the developing neocortex.

scholarly journals Activity-dependent modulation of synapse-regulating genes in astrocytes

eLife ◽  
2021 ◽  
Vol 10 ◽  
Author(s):  
Isabella Farhy-Tselnicker ◽  
Matthew M Boisvert ◽  
Hanqing Liu ◽  
Cari Dowling ◽  
Galina A Erikson ◽  
...  
Keyword(s):  
Calcium Release ◽  
Glutamate Release ◽  
Cortical Circuits ◽  
Temporal Expression ◽  
Synaptic Development ◽  
Neuronal Synapses ◽  
Single Nucleus ◽  
And Function ◽  
Mouse Visual Cortex ◽  
Activity Dependent

Astrocytes regulate the formation and function of neuronal synapses via multiple signals, however, what controls regional and temporal expression of these signals during development is unknown. We determined the expression profile of astrocyte synapse-regulating genes in the developing mouse visual cortex, identifying astrocyte signals that show differential temporal and layer-enriched expression. These patterns are not intrinsic to astrocytes, but regulated by visually-evoked neuronal activity, as they are absent in mice lacking glutamate release from thalamocortical terminals. Consequently, synapses remain immature. Expression of synapse-regulating genes and synaptic development are also altered when astrocyte signaling is blunted by diminishing calcium release from astrocyte stores. Single nucleus RNA sequencing identified groups of astrocytic genes regulated by neuronal and astrocyte activity, and a cassette of genes that show layer-specific enrichment. Thus, the development of cortical circuits requires coordinated signaling between astrocytes and neurons, highlighting astrocytes as a target to manipulate in neurodevelopmental disorders.

scholarly journals Temporal patterns of fluoxetine-induced plasticity in the mouse visual cortex

2018 ◽  
Author(s):  
Anna Steinzeig ◽  
Cecilia Cannarozzo ◽  
Eero Castren
Keyword(s):  
Visual Cortex ◽  
Critical Period ◽  
Ocular Dominance ◽  
Temporal Patterns ◽  
Monocular Deprivation ◽  
Adult Brain ◽  
Postnatal Life ◽  
Critical Periods ◽  
Mouse Visual Cortex

Heightened neuronal plasticity expressed during early postnatal life has been thought to permanently decline once critical periods have ended. For example, monocular deprivation is able to shift ocular dominance in the mouse visual cortex during the first months of life, but this effect is lost later in life. However, various treatments such as the antidepressant fluoxetine can reactivate a critical period-like plasticity in the adult brain. When monocular deprivation is supplemented with chronic fluoxetine administration, a major shift in ocular dominance is produced after the critical period has ended. In the current study, we characterized the temporal patterns of fluoxetine-induced plasticity in the adult mouse visual cortex, using in vivo optical imaging. We found that artificially-induced plasticity in ocular dominance extended beyond the duration of the naturally occurring critical period, and continued as long as fluoxetine was administered. However, this fluoxetine-induced plasticity period ended as soon as the drug was not given. Taken together, our data highlights how a combination of pharmacological treatment and environmental change could be used to improve strategies in antidepressant therapy in humans.

scholarly journals Activity-dependent modulation of NMDA receptors by endogenous zinc shapes dendritic function in cortical neurons.

2021 ◽  
Author(s):  
Annunziato Morabito ◽  
Yann Zerlaut ◽  
Benjamin Serraz ◽  
Romain Sala ◽  
Pierre Paoletti ◽  
...  
Keyword(s):  
Nmda Receptors ◽  
Cortical Neurons ◽  
Single Neuron ◽  
Pyramidal Neurons ◽  
Synaptic Activity ◽  
Cortical Circuits ◽  
New Perspective ◽  
Activity Dependent

Activation of NMDA receptors (NMDARs) has been proposed to be a key component of single neuron computations in vivo. However is unknown if specific mechanisms control the function of such receptors and modulate input-output transformations performed by cortical neurons under in vivo-like conditions. Here we found that in layer 2/3 pyramidal neurons (L2/3 PNs), repeated synaptic stimulation results in an activity-dependent decrease in NMDARs activity by vesicular zinc. Such a mechanism shifted the threshold for dendritic non-linearities and strongly reduced LTP induction. Modulation of NMDARs was cell- and pathway-specific, being present selectively in L2/3-L2/3 connections but absent in ascending bottom-up inputs originating from L4 neurons. Numerical simulations highlighted that activity-dependent modulation of NMDARs has an important influence in dendritic computations endowing L2/3 PN dendrites with the ability to sustain dendritic non-linear integrations constant across different regimes of synaptic activity like those found in vivo. The present results therefore provide a new perspective on the action of vesicular zinc in cortical circuits by highlighting the role of this endogenous ion in normalizing dendritic integration of PNs during a constantly changing synaptic input pattern.

scholarly journals Simultaneous two-photon imaging and two-photon optogenetics of cortical circuits in three dimensions

eLife ◽  
2018 ◽  
Vol 7 ◽  
Author(s):  
Weijian Yang ◽  
Luis Carrillo-Reid ◽  
Yuki Bando ◽  
Darcy S Peterka ◽  
Rafael Yuste
Keyword(s):  
Neural Activity ◽  
Pyramidal Neurons ◽  
Three Dimensions ◽  
Cortical Circuits ◽  
Two Photon ◽  
Simultaneous Imaging ◽  
All Optical ◽  
Holographic Approach ◽  
Mouse Visual Cortex

The simultaneous imaging and manipulating of neural activity could enable the functional dissection of neural circuits. Here we have combined two-photon optogenetics with simultaneous volumetric two-photon calcium imaging to measure and manipulate neural activity in mouse neocortex in vivo in three-dimensions (3D) with cellular resolution. Using a hybrid holographic approach, we simultaneously photostimulate more than 80 neurons over 150 μm in depth in layer 2/3 of the mouse visual cortex, while simultaneously imaging the activity of the surrounding neurons. We validate the usefulness of the method by photoactivating in 3D selected groups of interneurons, suppressing the response of nearby pyramidal neurons to visual stimuli in awake animals. Our all-optical approach could be used as a general platform to read and write neuronal activity.

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