scholarly journals Accelerated Hyper-Maturation of Parvalbumin Circuits in the Absence of MeCP2

2019 ◽  
Vol 30 (1) ◽  
pp. 256-268 ◽  
Author(s):  
Annarita Patrizi ◽  
Patricia N Awad ◽  
Bidisha Chattopadhyaya ◽  
Chloe Li ◽  
Graziella Di Cristo ◽  
...  
Keyword(s):  
Visual Cortex ◽  
Genetic Manipulation ◽  
Neurodevelopmental Disorder ◽  
Structural Complexity ◽  
Pyramidal Cells ◽  
Gabaergic Interneurons ◽  
Cortical Circuits ◽  
Structure Complexity ◽  
Deficient Mice

Abstract Methyl-CpG-binding protein 2 (MeCP2) mutations are the primary cause of Rett syndrome, a severe neurodevelopmental disorder. Cortical parvalbumin GABAergic interneurons (PV) make exuberant somatic connections onto pyramidal cells in the visual cortex of Mecp2-deficient mice, which contributes to silencing neuronal cortical circuits. This phenotype can be rescued independently of Mecp2 by environmental, pharmacological, and genetic manipulation. It remains unknown how Mecp2 mutation can result in abnormal inhibitory circuit refinement. In the present manuscript, we examined the development of GABAergic circuits in the primary visual cortex of Mecp2-deficient mice. We identified that PV circuits were the only GABAergic interneurons to be upregulated, while other interneurons were downregulated. Acceleration of PV cell maturation was accompanied by increased PV cells engulfment by perineuronal nets (PNNs) and by an increase of PV cellular and PNN structural complexity. Interestingly, selective deletion of Mecp2 from PV cells was sufficient to drive increased structure complexity of PNN. Moreover, the accelerated PV and PNN maturation was recapitulated in organotypic cultures. Our results identify a specific timeline of disruption of GABAergic circuits in the absence of Mecp2, indicating a possible cell-autonomous role of MeCP2 in the formation of PV cellular arbors and PNN structures in the visual cortex.

scholarly journals Aberrant development of excitatory circuits to inhibitory neurons in the primary visual cortex after neonatal binocular enucleation

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Rongkang Deng ◽  
Joseph P. Y. Kao ◽  
Patrick O. Kanold
Keyword(s):  
Visual Cortex ◽  
Nmda Receptors ◽  
Laser Scanning ◽  
Inhibitory Neurons ◽  
Gabaergic Interneurons ◽  
Cortical Circuits ◽  
Retinal Input ◽  
Layer 4 ◽  
Ampa And Nmda Receptors ◽  
Laser Scanning Photostimulation

AbstractThe development of GABAergic interneurons is important for the functional maturation of cortical circuits. After migrating into the cortex, GABAergic interneurons start to receive glutamatergic connections from cortical excitatory neurons and thus gradually become integrated into cortical circuits. These glutamatergic connections are mediated by glutamate receptors including AMPA and NMDA receptors and the ratio of AMPA to NMDA receptors decreases during development. Since previous studies have shown that retinal input can regulate the early development of connections along the visual pathway, we investigated if the maturation of glutamatergic inputs to GABAergic interneurons in the visual cortex requires retinal input. We mapped the spatial pattern of glutamatergic connections to layer 4 (L4) GABAergic interneurons in mouse visual cortex at around postnatal day (P) 16 by laser-scanning photostimulation and investigated the effect of binocular enucleations at P1/P2 on these patterns. Gad2-positive interneurons in enucleated animals showed an increased fraction of AMPAR-mediated input from L2/3 and a decreased fraction of input from L5/6. Parvalbumin-expressing (PV) interneurons showed similar changes in relative connectivity. NMDAR-only input was largely unchanged by enucleation. Our results show that retinal input sculpts the integration of interneurons into V1 circuits and suggest that the development of AMPAR- and NMDAR-only connections might be regulated differently.

scholarly journals Adaptive Integration in the Visual Cortex by Depressing Recurrent Cortical Circuits

2008 ◽  
Vol 20 (7) ◽  
pp. 1847-1872 ◽  
Author(s):  
Mark C. W. van Rossum ◽  
Matthijs A. A. van der Meer ◽  
Dengke Xiao ◽  
Mike W. Oram
Keyword(s):  
Visual Cortex ◽  
Physiological Data ◽  
High Contrast ◽  
Cortical Circuits ◽  
Response Latencies ◽  
Low Contrast ◽  
Visual Areas ◽  
Higher Visual Areas ◽  
Recurrent Connections

Neurons in the visual cortex receive a large amount of input from recurrent connections, yet the functional role of these connections remains unclear. Here we explore networks with strong recurrence in a computational model and show that short-term depression of the synapses in the recurrent loops implements an adaptive filter. This allows the visual system to respond reliably to deteriorated stimuli yet quickly to high-quality stimuli. For low-contrast stimuli, the model predicts long response latencies, whereas latencies are short for high-contrast stimuli. This is consistent with physiological data showing that in higher visual areas, latencies can increase more than 100 ms at low contrast compared to high contrast. Moreover, when presented with briefly flashed stimuli, the model predicts stereotypical responses that outlast the stimulus, again consistent with physiological findings. The adaptive properties of the model suggest that the abundant recurrent connections found in visual cortex serve to adapt the network's time constant in accordance with the stimulus and normalizes neuronal signals such that processing is as fast as possible while maintaining reliability.

scholarly journals Functional selectivity and specific connectivity of inhibitory neurons in primary visual cortex

2018 ◽  
Author(s):  
Petr Znamenskiy ◽  
Mean-Hwan Kim ◽  
Dylan R. Muir ◽  
Maria Florencia Iacaruso ◽  
Sonja B. Hofer ◽  
...  
Keyword(s):  
Visual Cortex ◽  
Primary Visual Cortex ◽  
Pyramidal Cells ◽  
Fine Tuning ◽  
Inhibitory Neurons ◽  
Local Network ◽  
Cortical Circuits ◽  
Sensory Stimuli ◽  
Excitatory Neurons ◽  
Strong Excitation

In the cerebral cortex, the interaction of excitatory and inhibitory synaptic inputs shapes the responses of neurons to sensory stimuli, stabilizes network dynamics1 and improves the efficiency and robustness of the neural code2–4. Excitatory neurons receive inhibitory inputs that track excitation5–8. However, how this co-tuning of excitation and inhibition is achieved by cortical circuits is unclear, since inhibitory interneurons are thought to pool the inputs of nearby excitatory cells and provide them with non-specific inhibition proportional to the activity of the local network9–13. Here we show that although parvalbumin-expressing (PV) inhibitory cells in mouse primary visual cortex make connections with the majority of nearby pyramidal cells, the strength of their synaptic connections is structured according to the similarity of the cells’ responses. Individual PV cells strongly inhibit those pyramidal cells that provide them with strong excitation and share their visual selectivity. This fine-tuning of synaptic weights supports co-tuning of inhibitory and excitatory inputs onto individual pyramidal cells despite dense connectivity between inhibitory and excitatory neurons. Our results indicate that individual PV cells are preferentially integrated into subnetworks of inter-connected, co-tuned pyramidal cells, stabilising their recurrent dynamics. Conversely, weak but dense inhibitory connectivity between subnetworks is sufficient to support competition between them, de-correlating their output. We suggest that the history and structure of correlated firing adjusts the weights of both inhibitory and excitatory connections, supporting stable amplification and selective recruitment of cortical subnetworks.

scholarly journals The essential role of feedback processing for figure-ground perception in mice

2018 ◽  
Author(s):  
Lisa Kirchberger ◽  
Sreedeep Mukherjee ◽  
Ulf H. Schnabel ◽  
Enny H. van Beest ◽  
Areg Barsegyan ◽  
...  
Keyword(s):  
Visual Cortex ◽  
Visual Perception ◽  
Essential Role ◽  
Pyramidal Cells ◽  
Neuronal Responses ◽  
Feedback Processing ◽  
Visual Areas ◽  
Higher Visual Areas ◽  
Delayed Phase

AbstractThe segregation of figures from the background is an important step in visual perception. In primary visual cortex, figures evoke stronger activity than backgrounds during a delayed phase of the neuronal responses, but it is unknown how this figure-ground modulation (FGM) arises and whether it is necessary for perception. Here we show, using optogenetic silencing in mice, that the delayed V1 response phase is necessary for figure-ground segregation. Neurons in higher visual areas also exhibit FGM and optogenetic silencing of higher areas reduced FGM in V1. In V1, figures elicited higher activity of vasoactive intestinal peptide-expressing (VIP) interneurons than the background, whereas figures suppressed somatostatin-positive interneurons, resulting in an increased activation of pyramidal cells. Optogenetic silencing of VIP neurons reduced FGM in V1, indicating that disinhibitory circuits contribute to FGM. Our results provide new insight in how lower and higher areas of the visual cortex interact to shape visual perception.

scholarly journals Laminar-specific cortico-cortical loops in mouse visual cortex

2019 ◽  
Author(s):  
Hedi Young ◽  
Beatriz Belbut ◽  
Margarida Baeta ◽  
Leopoldo Petreanu
Keyword(s):  
Visual Cortex ◽  
Cortical Circuits ◽  
Cortical Input ◽  
Cortical Connections ◽  
Cortical Hierarchy ◽  
Input Source ◽  
Innervation Patterns ◽  
Mouse Visual Cortex ◽  
Apical Dendrites

AbstractMany theories propose recurrent interactions across the cortical hierarchy, but it is unclear if cortical circuits are selectively wired to implement looped computations. Using subcellular channelrhodopsin-2-assisted circuit mapping in mouse visual cortex, we compared feedforward (FF) or feedback (FB) cortico-cortical input to cells projecting back to the input source (looped neurons) with cells projecting to a different cortical or subcortical area (non-looped neurons). Despite having different laminar innervation patterns, FF and FB afferents showed similar cell-type selectivity, making stronger connections with looped neurons versus non-looped neurons in layer (L) 5 and L6, but not in L2/3. FB inputs preferentially innervated the apical tufts of looped L5 neurons, but not their perisomatic dendrites. Our results reveal that interareal cortical connections are selectively wired into monosynaptic excitatory loops involving L6 and the apical dendrites of L5 neurons, supporting a role of these circuit elements in hierarchical recurrent computations.

scholarly journals GABAergic interneurons excite neonatal hippocampus in vivo

2020 ◽  
Vol 6 (24) ◽  
pp. eaba1430 ◽  
Author(s):  
Yasunobu Murata ◽  
Matthew T. Colonnese
Keyword(s):  
Visual Cortex ◽  
Synapse Formation ◽  
Reversal Potential ◽  
Pyramidal Cells ◽  
Gabaergic Neurons ◽  
Network Activity ◽  
Gabaergic Interneuron ◽  
Gabaergic Interneurons ◽  
Early Postnatal Development

GABAergic interneurons are proposed to be critical for early activity and synapse formation by directly exciting, rather than inhibiting, neurons in developing hippocampus and neocortex. However, the role of GABAergic neurons in the generation of neonatal network activity has not been tested in vivo, and recent studies have challenged the excitatory nature of early GABA. By locally manipulating interneuron activity in unanesthetized neonatal mice, we show that GABAergic neurons are excitatory in CA1 hippocampus at postnatal day 3 (P3) and are responsible for most of the spontaneous firing of pyramidal cells at that age. Hippocampal interneurons become inhibitory by P7, whereas visual cortex interneurons are already inhibitory by P3 and remain so throughout development. These regional and age-specific differences are the result of a change in chloride reversal potential, because direct activation of light-gated anion channels in glutamatergic neurons drives CA1 firing at P3, but silences it at P7 in CA1, and at all ages in visual cortex. This study in the intact brain reveals that GABAergic interneuron excitation is essential for network activity in neonatal hippocampus and confirms that visual cortical interneurons are inhibitory throughout early postnatal development.

scholarly journals The essential role of recurrent processing for figure-ground perception in mice

2021 ◽  
Vol 7 (27) ◽  
pp. eabe1833
Author(s):  
Lisa Kirchberger ◽  
Sreedeep Mukherjee ◽  
Ulf H. Schnabel ◽  
Enny H. van Beest ◽  
Areg Barsegyan ◽  
...  
Keyword(s):  
Visual Cortex ◽  
Visual Perception ◽  
Pyramidal Cells ◽  
Neuronal Responses ◽  
Visual Areas ◽  
Recurrent Processing ◽  
Higher Visual Areas ◽  
Delayed Phase ◽  
Insight Into

The segregation of figures from the background is an important step in visual perception. In primary visual cortex, figures evoke stronger activity than backgrounds during a delayed phase of the neuronal responses, but it is unknown how this figure-ground modulation (FGM) arises and whether it is necessary for perception. Here, we show, using optogenetic silencing in mice, that the delayed V1 response phase is necessary for figure-ground segregation. Neurons in higher visual areas also exhibit FGM and optogenetic silencing of higher areas reduced FGM in V1. In V1, figures elicited higher activity of vasoactive intestinal peptide–expressing (VIP) interneurons than the background, whereas figures suppressed somatostatin-positive interneurons, resulting in an increased activation of pyramidal cells. Optogenetic silencing of VIP neurons reduced FGM in V1, indicating that disinhibitory circuits contribute to FGM. Our results provide insight into how lower and higher areas of the visual cortex interact to shape visual perception.

scholarly journals Changes of MAP2 phosphorylation during brain development.

1995 ◽  
Vol 43 (12) ◽  
pp. 1269-1284 ◽  
Author(s):  
B M Riederer ◽  
E Draberova ◽  
V Viklicky ◽  
P Draber
Keyword(s):  
Monoclonal Antibodies ◽  
Visual Cortex ◽  
Conformational Changes ◽  
Splice Variants ◽  
Pyramidal Cells ◽  
Neuronal Morphology ◽  
Neuronal Marker ◽  
Molecular Stability ◽  
Granular Layers

The microtubule-associated protein MAP2 is essential for development of early neuronal morphology and maintenance of adult neuronal morphology. Several splice variants exist, MAP2a-d, with a lack of MAP2a in cat brain. MAP2 is widely used as a neuronal marker. In this study we compared five monoclonal antibodies (MAbs) against MAP2. They show differences in the immunocytochemical distribution of MAP2 isoforms during development of the visual cortex and cerebellum of the cat. Local and temporal differences were seen with MAb AP18, an antibody directed against a phosphorylation-dependent epitope near the N-terminal end. In large pyramidal dendrites in visual cortex, the AP18 epitope remained in parts immunoreactive after treatment with alkaline phosphatase. Three MAbs, AP14, MT-01, and MT-02, recognized the central region of the MAP2b molecule, which is not present in MAP2c and 2d, and reacted with phosphorylation-independent epitopes. During the first postnatal week the immunostaining in cerebellum differed between antibodies in that some cellular elements in external and internal granular layers and Purkinje cells were stained to various degrees, whereas at later stages staining patterns were similar. At early stages, antibody MT-02 stained cell bodies and dendrites in cerebral cortex and cerebellum. With progressing maturation, immunoreactivity became restricted to distal parts of apical dendrites of pyramidal cells and was absent from perikarya and finer proximal dendrites in cortex. MT-02 did not stain MAP2 in cerebellum of adult animals. This study demonstrates that the immunocytochemical detection of MAP2 depends on modifications such as phosphorylation and conformational changes of the molecule, and that MAP2 staining patterns differ between MAbs. Phosphorylation and specific conformations in the molecule may be essential for modulating function and molecular stability of MAP2, and monoclonal antibodies against such sites may provide tools for studying the functional role of modifications.

scholarly journals Ube3a loss increases excitability and blunts orientation tuning in the visual cortex of Angelman syndrome model mice

2017 ◽  
Vol 118 (1) ◽  
pp. 634-646 ◽  
Author(s):  
Michael L. Wallace ◽  
Geeske M. van Woerden ◽  
Ype Elgersma ◽  
Spencer L. Smith ◽  
Benjamin D. Philpot
Keyword(s):  
Visual Cortex ◽  
Angelman Syndrome ◽  
Pyramidal Neurons ◽  
Neurodevelopmental Disorder ◽  
Inhibitory Neurons ◽  
Electrophysiological Recording ◽  
Orientation Tuning ◽  
Visual Cortical ◽  
Deficient Mice

Angelman syndrome (AS) is a neurodevelopmental disorder caused by loss of the maternally inherited allele of UBE3A. Ube3aSTOP/p+ mice recapitulate major features of AS in humans and allow conditional reinstatement of maternal Ube3a with the expression of Cre recombinase. We have recently shown that AS model mice exhibit reduced inhibitory drive onto layer (L)2/3 pyramidal neurons of visual cortex, which contributes to a synaptic excitatory/inhibitory imbalance. However, it remains unclear how this loss of inhibitory drive affects neural circuits in vivo. Here we examined visual cortical response properties in individual neurons to explore the consequences of Ube3a loss on intact cortical circuits and processing. Using in vivo patch-clamp electrophysiology, we measured the visually evoked responses to square-wave drifting gratings in L2/3 regular-spiking (RS) neurons in control mice, Ube3a-deficient mice, and mice in which Ube3a was conditionally reinstated in GABAergic neurons. We found that Ube3a-deficient mice exhibited enhanced pyramidal neuron excitability in vivo as well as weaker orientation tuning. These observations are the first to show alterations in cortical computation in an AS model, and they suggest a basis for cortical dysfunction in AS. NEW & NOTEWORTHY Angelman syndrome (AS) is a severe neurodevelopmental disorder caused by the loss of the gene UBE3A. Using electrophysiological recording in vivo, we describe visual cortical dysfunctions in a mouse model of AS. Aberrant cellular properties in AS model mice could be improved by reinstating Ube3a in inhibitory neurons. These findings suggest that inhibitory neurons play a substantial role in the pathogenesis of AS.

scholarly journals Laminar-specific cortico-cortical loops in mouse visual cortex

eLife ◽  
2021 ◽  
Vol 10 ◽  
Author(s):  
Hedi Young ◽  
Beatriz Belbut ◽  
Margarida Baeta ◽  
Leopoldo Petreanu
Keyword(s):  
Visual Cortex ◽  
Synaptic Input ◽  
Cortical Circuits ◽  
Cell Type ◽  
Cortical Hierarchy ◽  
Selective Modulation ◽  
Input Source ◽  
Similar Cell ◽  
Mouse Visual Cortex

Many theories propose recurrent interactions across the cortical hierarchy, but it is unclear if cortical circuits are selectively wired to implement looped computations. Using subcellular channelrhodopsin-2-assisted circuit mapping in mouse visual cortex, we compared feedforward (FF) or feedback (FB) cortico-cortical (CC) synaptic input to cells projecting back to the input source (looped neurons) with cells projecting to a different cortical or subcortical area. FF and FB afferents showed similar cell-type selectivity, making stronger connections with looped neurons than with other projection types in layer (L)5 and L6, but not in L2/3, resulting in selective modulation of activity in looped neurons. In most cases, stronger connections in looped L5 neurons were located on their apical tufts, but not on their perisomatic dendrites. Our results reveal that CC connections are selectively wired to form monosynaptic excitatory loops and support a differential role of supragranular and infragranular neurons in hierarchical recurrent computations.

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