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A disinhibitory microcircuit initiates critical period plasticity in the visu...Taruna Ikrar
Earlysensoryexperienceinstructsthematurationofneuralcircuitry in the cortex1,2. This has been studied extensively in the primary visualcortex,inwhichlossofvisiontooneeyepermanentlydegrades corticalresponsivenesstothateye3,4,aphenomenonknownasocular dominance plasticity (ODP). Cortical inhibition mediates this process4–6,butthepreciseroleofspecificclassesofinhibitoryneurons in ODP is controversial. Here we report that evoked firing rates of binocular excitatory neurons in the primary visual cortex immediatelydropbyhalfwhenvisionisrestrictedtooneeye,butgradually return to normal over the followingtwenty-four hours, despite the fact that vision remains restricted to one eye. This restoration of binocular-like excitatory firing rates after monocular deprivation resultsfromarapid,althoughtransient,reductioninthefiringrates of fast-spiking, parvalbumin-positive (PV) interneurons, which in turncanbeattributedtoadecreaseinlocalexcitatorycircuitinput onto PV interneurons.This reduction in PV-cell-evoked responses after monocular lid suture is restricted to the critical period for ODPandappearstobenecessaryforsubsequentshiftsinexcitatory ODP. Pharmacologically enhancing inhibition at the time of sight deprivation blocks ODP and, conversely, pharmacogenetic reduction of PV cell firing rates can extend the critical period for ODP. Thesefindingsdefinethemicrocircuitchangesinitiatingcompetitive
plasticityduringcriticalperiodsofcorticaldevelopment.Moreover, they show that the restoration of evoked firing rates of layer 2/3 pyramidal neurons by PV-specific disinhibition is a key step in the progression of ODP.
An inhibitory pull–push circuit in frontal cortexTaruna Ikrar
Push–pull is a canonical computation of excitatory cortical circuits. By contrast, we identify a pull–push inhibitory circuit in frontal cortex that originates in vasoactive intestinal polypeptide (VIP)-expressing interneurons. During arousal, VIP cells rapidly and directly inhibit pyramidal neurons; VIP cells also indirectly excite these pyramidal neurons via parallel disinhibition. Thus, arousal exerts a feedback pull–push influence on excitatory neurons—an inversion of the canonical push–pull of feedforward input.
Pten and eph b4 regulate the establishment of perisomatic inhibition in mouse...Taruna Ikrar
Perisomatic inhibition of pyramidal neurons is established by fast-spiking, parvalbuminexpressing interneurons (PV cells). Failure to assemble adequate perisomatic inhibition is thought to underlie the aetiology of neurological dysfunction in seizures, autism spectrum disorders and schizophrenia. Here we show that in mouse visual cortex, strong perisomatic inhibition does not develop if PV cells lack a single copy of Pten. PTEN signalling appears to drive the assembly of perisomatic inhibition in an experience-dependent manner by suppressing the expression of EphB4; PVcells hemizygous for Pten show an B2-fold increase in expression of EphB4, and over-expression of EphB4 in adult PV cells causes a dismantling of perisomatic inhibition. These findings implicate a molecular disinhibitory mechanism driving the establishment of perisomatic inhibition whereby visual experience enhances Pten signalling, resulting in the suppression of EphB4 expression; this relieves a native synaptic repulsion between PV cells and pyramidal neurons, thereby promoting the assembly of perisomatic inhibition.
Abstract In the mammalian neocortex, excitatory neurons provide excitation in both columnar and laminar dimensions, which is modulated further by inhibitory neurons. However, our understanding of intracortical excitatory and inhibitory synaptic inputs in relation to principal excitatory neurons remains incomplete, and it is unclear how local excitatory and inhibitory synaptic connections to excitatory neurons are spatially organized on a layer-by-layer basis. In the present study, we combined whole cell recordings with laser scanning photostimulation via glutamate uncaging to map excitatory and inhibitory synaptic inputs to single excitatory neurons throughout cortical layers 2/3–6 in the mouse primary visual cortex (V1). We find that synaptic input sources of excitatory neurons span the radial columns of laminar microcircuits, and excitatory neurons in different V1 laminae exhibit distinct patterns of layer-specific organizationofexcitatoryinputs.Remarkably,thespatialextentofinhibitoryinputsofexcitatory neurons for a given layer closely mirrors that of their excitatory input sources, indicating that excitatory and inhibitory synaptic connectivity is spatially balanced across excitatory neuronal networks. Strong interlaminar inhibitory inputs are found, particularly for excitatory neurons in layers 2/3 and 5. This differs from earlier studies reporting that inhibitory cortical connections to excitatory neurons are generally localized within the same cortical layer. On the basis of the functional mapping assays, we conducted a quantitative assessment of both excitatory and inhibitory synaptic laminar connections to excitatory cells at single cell resolution, establishing precise layer-by-layer synaptic wiring diagrams of excitatory neurons in the visual cortex.
A characteristic of the developing mammalian visual system is a brief interval of plasticity, termed the “critical period,” when the circuitry of
primary visual cortex is most sensitive to perturbation of visual experience. Depriving one eye of vision (monocular deprivation [MD]) during
the critical period alters ocular dominance (OD) by shifting the responsiveness of neurons in visual cortex to favor the nondeprived eye. A
disinhibitory microcircuit involving parvalbumin-expressing (PV) interneurons initiates this OD plasticity. The gene encoding the neuronal
nogo-66-receptor1(ngr1/rtn4r) is required to close the critical period.Herewecombinedmousegenetics, electrophysiology,andcircuitmapping
with laser-scanning photostimulation to investigate whether disinhibition is confined to the critical period by ngr1.We demonstrate that ngr1
mutant mice retain plasticity characteristic of the critical period as adults, and that ngr1 operates within PV interneurons to restrict the loss of
intracortical excitatory synaptic input following MD in adult mice, and this disinhibition induces a “lower PV network configuration” in both
critical-period wild-type miceandadult ngr1/mice.Wepropose that ngr1 limits disinhibition to close the critical period forODplasticityand
that a decrease in PV expression levels reports the diminished recent cumulative activity of these interneurons.
A disinhibitory microcircuit initiates critical period plasticity in the visu...Taruna Ikrar
Early sensory experience instructs the maturation of neural circuitry in the cortex1, 2. This has been studied extensively in the primary visual cortex, in which loss of vision to one eye permanently degrades cortical responsiveness to that eye3, 4, a phenomenon known as ocular dominance plasticity (ODP). Cortical inhibition mediates this process4, 5, 6, but the precise role of specific classes of inhibitory neurons in ODP is controversial. Here we report that evoked firing rates of binocular excitatory neurons in the primary visual cortex immediately drop by half when vision is restricted to one eye, but gradually return to normal over the following twenty-four hours, despite the fact that vision remains restricted to one eye. This restoration of binocular-like excitatory firing rates after monocular deprivation results from a rapid, although transient, reduction in the firing rates of fast-spiking, parvalbumin-positive (PV) interneurons, which in turn can be attributed to a decrease in local excitatory circuit input onto PV interneurons. This reduction in PV-cell-evoked responses after monocular lid suture is restricted to the critical period for ODP and appears to be necessary for subsequent shifts in excitatory ODP. Pharmacologically enhancing inhibition at the time of sight deprivation blocks ODP and, conversely, pharmacogenetic reduction of PV cell firing rates can extend the critical period for ODP. These findings define the microcircuit changes initiating competitive plasticity during critical periods of cortical development. Moreover, they show that the restoration of evoked firing rates of layer 2/3 pyramidal neurons by PV-specific disinhibition is a key step in the progression of ODP.
Content personalisation is becoming more prevalent. A site, it's content and/or it's products, change dynamically according to the specific needs of the user. SEO needs to ensure we do not fall behind of this trend.
A disinhibitory microcircuit initiates critical period plasticity in the visu...Taruna Ikrar
Earlysensoryexperienceinstructsthematurationofneuralcircuitry in the cortex1,2. This has been studied extensively in the primary visualcortex,inwhichlossofvisiontooneeyepermanentlydegrades corticalresponsivenesstothateye3,4,aphenomenonknownasocular dominance plasticity (ODP). Cortical inhibition mediates this process4–6,butthepreciseroleofspecificclassesofinhibitoryneurons in ODP is controversial. Here we report that evoked firing rates of binocular excitatory neurons in the primary visual cortex immediatelydropbyhalfwhenvisionisrestrictedtooneeye,butgradually return to normal over the followingtwenty-four hours, despite the fact that vision remains restricted to one eye. This restoration of binocular-like excitatory firing rates after monocular deprivation resultsfromarapid,althoughtransient,reductioninthefiringrates of fast-spiking, parvalbumin-positive (PV) interneurons, which in turncanbeattributedtoadecreaseinlocalexcitatorycircuitinput onto PV interneurons.This reduction in PV-cell-evoked responses after monocular lid suture is restricted to the critical period for ODPandappearstobenecessaryforsubsequentshiftsinexcitatory ODP. Pharmacologically enhancing inhibition at the time of sight deprivation blocks ODP and, conversely, pharmacogenetic reduction of PV cell firing rates can extend the critical period for ODP. Thesefindingsdefinethemicrocircuitchangesinitiatingcompetitive
plasticityduringcriticalperiodsofcorticaldevelopment.Moreover, they show that the restoration of evoked firing rates of layer 2/3 pyramidal neurons by PV-specific disinhibition is a key step in the progression of ODP.
An inhibitory pull–push circuit in frontal cortexTaruna Ikrar
Push–pull is a canonical computation of excitatory cortical circuits. By contrast, we identify a pull–push inhibitory circuit in frontal cortex that originates in vasoactive intestinal polypeptide (VIP)-expressing interneurons. During arousal, VIP cells rapidly and directly inhibit pyramidal neurons; VIP cells also indirectly excite these pyramidal neurons via parallel disinhibition. Thus, arousal exerts a feedback pull–push influence on excitatory neurons—an inversion of the canonical push–pull of feedforward input.
Pten and eph b4 regulate the establishment of perisomatic inhibition in mouse...Taruna Ikrar
Perisomatic inhibition of pyramidal neurons is established by fast-spiking, parvalbuminexpressing interneurons (PV cells). Failure to assemble adequate perisomatic inhibition is thought to underlie the aetiology of neurological dysfunction in seizures, autism spectrum disorders and schizophrenia. Here we show that in mouse visual cortex, strong perisomatic inhibition does not develop if PV cells lack a single copy of Pten. PTEN signalling appears to drive the assembly of perisomatic inhibition in an experience-dependent manner by suppressing the expression of EphB4; PVcells hemizygous for Pten show an B2-fold increase in expression of EphB4, and over-expression of EphB4 in adult PV cells causes a dismantling of perisomatic inhibition. These findings implicate a molecular disinhibitory mechanism driving the establishment of perisomatic inhibition whereby visual experience enhances Pten signalling, resulting in the suppression of EphB4 expression; this relieves a native synaptic repulsion between PV cells and pyramidal neurons, thereby promoting the assembly of perisomatic inhibition.
Abstract In the mammalian neocortex, excitatory neurons provide excitation in both columnar and laminar dimensions, which is modulated further by inhibitory neurons. However, our understanding of intracortical excitatory and inhibitory synaptic inputs in relation to principal excitatory neurons remains incomplete, and it is unclear how local excitatory and inhibitory synaptic connections to excitatory neurons are spatially organized on a layer-by-layer basis. In the present study, we combined whole cell recordings with laser scanning photostimulation via glutamate uncaging to map excitatory and inhibitory synaptic inputs to single excitatory neurons throughout cortical layers 2/3–6 in the mouse primary visual cortex (V1). We find that synaptic input sources of excitatory neurons span the radial columns of laminar microcircuits, and excitatory neurons in different V1 laminae exhibit distinct patterns of layer-specific organizationofexcitatoryinputs.Remarkably,thespatialextentofinhibitoryinputsofexcitatory neurons for a given layer closely mirrors that of their excitatory input sources, indicating that excitatory and inhibitory synaptic connectivity is spatially balanced across excitatory neuronal networks. Strong interlaminar inhibitory inputs are found, particularly for excitatory neurons in layers 2/3 and 5. This differs from earlier studies reporting that inhibitory cortical connections to excitatory neurons are generally localized within the same cortical layer. On the basis of the functional mapping assays, we conducted a quantitative assessment of both excitatory and inhibitory synaptic laminar connections to excitatory cells at single cell resolution, establishing precise layer-by-layer synaptic wiring diagrams of excitatory neurons in the visual cortex.
A characteristic of the developing mammalian visual system is a brief interval of plasticity, termed the “critical period,” when the circuitry of
primary visual cortex is most sensitive to perturbation of visual experience. Depriving one eye of vision (monocular deprivation [MD]) during
the critical period alters ocular dominance (OD) by shifting the responsiveness of neurons in visual cortex to favor the nondeprived eye. A
disinhibitory microcircuit involving parvalbumin-expressing (PV) interneurons initiates this OD plasticity. The gene encoding the neuronal
nogo-66-receptor1(ngr1/rtn4r) is required to close the critical period.Herewecombinedmousegenetics, electrophysiology,andcircuitmapping
with laser-scanning photostimulation to investigate whether disinhibition is confined to the critical period by ngr1.We demonstrate that ngr1
mutant mice retain plasticity characteristic of the critical period as adults, and that ngr1 operates within PV interneurons to restrict the loss of
intracortical excitatory synaptic input following MD in adult mice, and this disinhibition induces a “lower PV network configuration” in both
critical-period wild-type miceandadult ngr1/mice.Wepropose that ngr1 limits disinhibition to close the critical period forODplasticityand
that a decrease in PV expression levels reports the diminished recent cumulative activity of these interneurons.
A disinhibitory microcircuit initiates critical period plasticity in the visu...Taruna Ikrar
Early sensory experience instructs the maturation of neural circuitry in the cortex1, 2. This has been studied extensively in the primary visual cortex, in which loss of vision to one eye permanently degrades cortical responsiveness to that eye3, 4, a phenomenon known as ocular dominance plasticity (ODP). Cortical inhibition mediates this process4, 5, 6, but the precise role of specific classes of inhibitory neurons in ODP is controversial. Here we report that evoked firing rates of binocular excitatory neurons in the primary visual cortex immediately drop by half when vision is restricted to one eye, but gradually return to normal over the following twenty-four hours, despite the fact that vision remains restricted to one eye. This restoration of binocular-like excitatory firing rates after monocular deprivation results from a rapid, although transient, reduction in the firing rates of fast-spiking, parvalbumin-positive (PV) interneurons, which in turn can be attributed to a decrease in local excitatory circuit input onto PV interneurons. This reduction in PV-cell-evoked responses after monocular lid suture is restricted to the critical period for ODP and appears to be necessary for subsequent shifts in excitatory ODP. Pharmacologically enhancing inhibition at the time of sight deprivation blocks ODP and, conversely, pharmacogenetic reduction of PV cell firing rates can extend the critical period for ODP. These findings define the microcircuit changes initiating competitive plasticity during critical periods of cortical development. Moreover, they show that the restoration of evoked firing rates of layer 2/3 pyramidal neurons by PV-specific disinhibition is a key step in the progression of ODP.