scholarly journals An Extracellular Perspective on CNS Maturation: Perineuronal Nets and the Control of Plasticity

2021 ◽  
Vol 22 (5) ◽  
pp. 2434
Author(s):  
Daniela Carulli ◽  
Joost Verhaagen
Keyword(s):  
Critical Period ◽  
Brain Plasticity ◽  
Time Windows ◽  
Adult Brain ◽  
Mammalian Brain ◽  
Postnatal Life ◽  
Perineuronal Nets ◽  
Critical Periods ◽  
Perineuronal Net ◽  
Memory Processes

During restricted time windows of postnatal life, called critical periods, neural circuits are highly plastic and are shaped by environmental stimuli. In several mammalian brain areas, from the cerebral cortex to the hippocampus and amygdala, the closure of the critical period is dependent on the formation of perineuronal nets. Perineuronal nets are a condensed form of an extracellular matrix, which surrounds the soma and proximal dendrites of subsets of neurons, enwrapping synaptic terminals. Experimentally disrupting perineuronal nets in adult animals induces the reactivation of critical period plasticity, pointing to a role of the perineuronal net as a molecular brake on plasticity as the critical period closes. Interestingly, in the adult brain, the expression of perineuronal nets is remarkably dynamic, changing its plasticity-associated conditions, including memory processes. In this review, we aimed to address how perineuronal nets contribute to the maturation of brain circuits and the regulation of adult brain plasticity and memory processes in physiological and pathological conditions.

scholarly journals The Function of Activity-Regulated Genes in the Nervous System

2009 ◽  
Vol 89 (4) ◽  
pp. 1079-1103 ◽  
Author(s):  
Sven Loebrich ◽  
Elly Nedivi
Keyword(s):  
Transcriptional Control ◽  
Brain Plasticity ◽  
Neuronal Morphology ◽  
Adult Brain ◽  
Mammalian Brain ◽  
Current View ◽  
Control Mechanisms ◽  
Critical Periods ◽  
Cellular Functions ◽  
Dynamic Tuning

The mammalian brain is plastic in the sense that it shows a remarkable capacity for change throughout life. The contribution of neuronal activity to brain plasticity was first recognized in relation to critical periods of development, when manipulating the sensory environment was found to profoundly affect neuronal morphology and receptive field properties. Since then, a growing body of evidence has established that brain plasticity extends beyond development and is an inherent feature of adult brain function, spanning multiple domains, from learning and memory to adaptability of primary sensory maps. Here we discuss evolution of the current view that plasticity of the adult brain derives from dynamic tuning of transcriptional control mechanisms at the neuronal level, in response to external and internal stimuli. We then review the identification of “plasticity genes” regulated by changes in the levels of electrical activity, and how elucidating their cellular functions has revealed the intimate role transcriptional regulation plays in fundamental aspects of synaptic transmission and circuit plasticity that occur in the brain on an every day basis.

scholarly journals Pharmacological and optical activation of TrkB in Parvalbumin interneurons regulate intrinsic states to orchestrate cortical plasticity

2021 ◽  
Author(s):  
Frederike Winkel ◽  
Maria Ryazantseva ◽  
Mathias B. Voigt ◽  
Giuliano Didio ◽  
Antonia Lilja ◽  
...  
Keyword(s):  
Environmental Enrichment ◽  
Pyramidal Neurons ◽  
Cortical Plasticity ◽  
Brain Plasticity ◽  
Antidepressant Treatment ◽  
Ocular Dominance ◽  
Adult Brain ◽  
Postnatal Life ◽  
Critical Periods ◽  
Cortical Networks

AbstractElevated states of brain plasticity typical for critical periods of early postnatal life can be reinstated in the adult brain through interventions, such as antidepressant treatment and environmental enrichment, and induced plasticity may be critical for the antidepressant action. Parvalbumin-positive (PV) interneurons regulate the closure of developmental critical periods and can alternate between high and low plasticity states in response to experience in adulthood. We now show that PV plasticity states and cortical networks are regulated through the activation of TrkB neurotrophin receptors. Visual cortical plasticity induced by fluoxetine, a widely prescribed selective serotonin reuptake inhibitor (SSRI) antidepressant, was lost in mice with reduced expression of TrkB in PV interneurons. Conversely, optogenetic gain-of-function studies revealed that activation of an optically activatable TrkB (optoTrkB) specifically in PV interneurons switches adult cortical networks into a state of elevated plasticity within minutes by decreasing the intrinsic excitability of PV interneurons, recapitulating the effects of fluoxetine. TrkB activation shifted cortical networks towards a low PV configuration, promoting oscillatory synchrony, increased excitatory-inhibitory balance, and ocular dominance plasticity. OptoTrkB activation promotes the phosphorylation of Kv3.1 channels and reduces the expression of Kv3.2 mRNA providing a mechanism for the lower excitability. In addition, decreased expression and puncta of Synaptotagmin2 (Syt2), a presynaptic marker of PV interneurons involved in Ca2+-dependent neurotransmitter release, suggests lower inputs onto pyramidal neurons suppressing feed-forward inhibition. Together, the results provide mechanistic insights into how TrkB activation in PV interneurons orchestrates the activity of cortical networks and mediating antidepressant responses in the adult brain.

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 Postnatal fluoxetine treatment alters perineuronal net formation and maintenance in the hippocampus

2020 ◽  
Author(s):  
Sourish Mukhopadhyay ◽  
Ashmita Chatterjee ◽  
Praachi Tiwari ◽  
Utkarsha Ghai ◽  
Vidita A. Vaidya
Keyword(s):  
Extracellular Matrix ◽  
Critical Period ◽  
Developmental Trajectory ◽  
Postnatal Life ◽  
Perineuronal Nets ◽  
Receptor Subunit ◽  
Neuronal Activation ◽  
Perineuronal Net ◽  
Hippocampal Subfields ◽  
The Impact

AbstractElevation of serotonin via postnatal fluoxetine (PNFlx) treatment during critical temporal windows is hypothesized to perturb the development of limbic circuits thus establishing a substratum for persistent disruption of mood-related behavior. We examined the impact of PNFlx treatment on the formation and maintenance of perineuronal nets (PNNs), extracellular matrix (ECM) structures that deposit primarily around inhibitory interneurons, and mark the closure of critical period plasticity. PNFlx treatment evoked a significant decline in PNN number, with a robust reduction in PNNs deposited around parvalbumin (PV) interneurons, within the CA1 and CA3 hippocampal subfields at postnatal day 21 in Sprague-Dawley rat pups. While the reduction in CA1 subfield PNN number was still observed in adulthood, we observed no change in colocalization of PV-positive interneurons with PNNs in the hippocampi of adult PNFlx animals. PNFlx treatment did not alter hippocampal parvalbumin, calretinin, or reelin-positive neuron numbers in PNFlx animals at P21 or in adulthood. We did observe a small, but significant increase in somatostatin (SST)-positive interneurons in the DG subfield of PNFlx-treated animals in adulthood. This was accompanied by altered GABA-A receptor subunit composition, increased dendritic complexity of apical dendrites of CA1 pyramidal neurons, and enhanced neuronal activation revealed by increased c-Fos-positive cell numbers within hippocampi of PNFlx-treated animals in adulthood. These results indicate that PNFlx treatment alters the developmental trajectory of PNNs within the hippocampus, raising the possibility of a disruption of critical period plasticity and the establishment of an altered excitation-inhibition balance within this key limbic brain region.Significance StatementClinical and preclinical studies indicate that developmental exposure to fluoxetine programs persistent dysregulation of mood-related behaviors. This is hypothesized to involve the disruption of the normal development of key brain regions, such as the hippocampus that regulate mood behaviors. We show that postnatal exposure to fluoxetine alters hippocampal perineuronal nets (PNNs), extracellular matrix structures that regulate plasticity and mark the closure of critical periods. The decline in PNNs is noted in early postnatal life, and persists into adulthood in specific hippocampal subfields. Adult animals with a history of postnatal fluoxetine exposure exhibit altered numbers of somatostatin interneurons, GABA receptor subunit expression and neuronal activation within the hippocampus. This indicates that postnatal fluoxetine disrupts the normal developmental trajectory of the hippocampus.

Pharmacological Manipulation of Critical Period Plasticity

2018 ◽  
Author(s):  
Ramon Guirado ◽  
Eero Castrén
Keyword(s):  
Critical Period ◽  
Adult Brain ◽  
Brain Disorders ◽  
Critical Periods ◽  
Pharmacological Treatments ◽  
New Paradigm ◽  
Early Postnatal Development ◽  
Pharmacological Manipulation ◽  
Efficient Recovery ◽  
Activity Dependent

Neuronal networks are refined through an activity-dependent competition during critical periods of early postnatal development. Recent studies have shown that critical period plasticity is influenced by a number of environmental factors, including drugs that are widely used for the treatment of brain disorders. These findings suggest a new paradigm, where pharmacological treatments can be used to open critical period–like plasticity in the adult brain. The plastic networks can then be modified through rehabilitation or psychotherapy to rewire those abnormally wired during development. This kind of combination of pharmacotherapy with physical or psychological rehabilitation may open a new opportunity for a more efficient recovery of a number of neurological and neuropsychiatric disorders.

scholarly journals Gene Expression Patterns Underlying the Reinstatement of Plasticity in the Adult Visual System

2013 ◽  
Vol 2013 ◽  
pp. 1-8 ◽  
Author(s):  
Ettore Tiraboschi ◽  
Ramon Guirado ◽  
Dario Greco ◽  
Petri Auvinen ◽  
Jose Fernando Maya-Vetencourt ◽  
...  
Keyword(s):  
Gene Expression ◽  
Visual Cortex ◽  
Large Scale ◽  
Molecular Mechanisms ◽  
Expression Patterns ◽  
Monocular Deprivation ◽  
Adult Brain ◽  
Gene Expression Patterns ◽  
Postnatal Life ◽  
Critical Periods

The nervous system is highly sensitive to experience during early postnatal life, but this phase of heightened plasticity decreases with age. Recent studies have demonstrated that developmental-like plasticity can be reactivated in the visual cortex of adult animals through environmental or pharmacological manipulations. These findings provide a unique opportunity to study the cellular and molecular mechanisms of adult plasticity. Here we used the monocular deprivation paradigm to investigate large-scale gene expression patterns underlying the reinstatement of plasticity produced by fluoxetine in the adult rat visual cortex. We found changes, confirmed with RT-PCRs, in gene expression in different biological themes, such as chromatin structure remodelling, transcription factors, molecules involved in synaptic plasticity, extracellular matrix, and excitatory and inhibitory neurotransmission. Our findings reveal a key role for several molecules such as the metalloproteases Mmp2 and Mmp9 or the glycoprotein Reelin and open up new insights into the mechanisms underlying the reopening of the critical periods in the adult brain.

scholarly journals A Late Critical Period for Frequency Modulated Sweeps in the Mouse Auditory System

2019 ◽  
Vol 30 (4) ◽  
pp. 2586-2599 ◽  
Author(s):  
Stitipragyan Bhumika ◽  
Mari Nakamura ◽  
Patricia Valerio ◽  
Magdalena Solyga ◽  
Henrik Lindén ◽  
...  
Keyword(s):  
Auditory Cortex ◽  
Auditory System ◽  
Critical Period ◽  
Noise Exposure ◽  
Functional Organization ◽  
Time Windows ◽  
Immunohistochemical Analysis ◽  
Critical Periods ◽  
Complex Sounds

Abstract Neuronal circuits are shaped by experience during time windows of increased plasticity in postnatal development. In the auditory system, the critical period for the simplest sounds—pure frequency tones—is well defined. Critical periods for more complex sounds remain to be elucidated. We used in vivo electrophysiological recordings in the mouse auditory cortex to demonstrate that passive exposure to frequency modulated sweeps (FMS) from postnatal day 31 to 38 leads to long-term changes in the temporal representation of sweep directions. Immunohistochemical analysis revealed a decreased percentage of layer 4 parvalbumin-positive (PV+) cells during this critical period, paralleled with a transient increase in responses to FMS, but not to pure tones. Preventing the PV+ cell decrease with continuous white noise exposure delayed the critical period onset, suggesting a reduction in inhibition as a mechanism for this plasticity. Our findings shed new light on the dependence of plastic windows on stimulus complexity that persistently sculpt the functional organization of the auditory cortex.

scholarly journals Chondroitinase and antidepressants promote plasticity by releasing TRKB from dephosphorylating control of PTPσ in parvalbumin neurons

2020 ◽  
Author(s):  
Angelina Lesnikova ◽  
Plinio Cabrera Casarotto ◽  
Senem Merve Fred ◽  
Mikko Voipio ◽  
Frederike Winkel ◽  
...  
Keyword(s):  
Visual Cortex ◽  
Protein Tyrosine Phosphatase ◽  
Critical Period ◽  
Antidepressant Treatment ◽  
Tyrosine Phosphatase ◽  
Adult Brain ◽  
Neurotrophin Receptor ◽  
Perineuronal Nets ◽  
Protein Tyrosine ◽  
Chondroitin Sulphate Proteoglycans

AbstractPerineuronal nets (PNNs) are an extracellular matrix structure rich in chondroitin sulphate proteoglycans (CSPGs) which preferentially encase parvalbumin-containing (PV+) interneurons. PNNs restrict cortical network plasticity but the molecular mechanisms involved are unclear. We found that reactivation of ocular dominance plasticity in the adult visual cortex induced by chondroitinase (chABC)-mediated PNN removal requires intact signaling by the neurotrophin receptor TRKB in PV+ neurons. Additionally, we demonstrate that chABC increases TRKB phosphorylation (pTRKB), while PNN component aggrecan attenuates BDNF-induced pTRKB in cortical neurons in culture. We further found that protein tyrosine phosphatase sigma (PTPσ, PTPRS), receptor for CSPGs, interacts with TRKB and restricts TRKB phosphorylation. PTPσ deletion increases phosphorylation of TRKB in vitro and in vivo in male and female mice, and juvenile-like plasticity is retained in the visual cortex of adult PTPσ deficient mice (PTPσ+/-). The antidepressant drug fluoxetine, which is known to promote TRKB phosphorylation and reopen critical period-like plasticity in the adult brain, disrupts the interaction between TRKB and PTPσ by binding to the transmembrane domain of TRKB. We propose that both chABC and fluoxetine reopen critical period-like plasticity in the adult visual cortex by promoting TRKB signaling in PV+ neurons through inhibition of TRKB dephosphorylation by the PTPσ-CSPG complex.Significance statementCritical period-like plasticity can be reactivated in the adult visual cortex through disruption of perineuronal nets (PNNs) by chondroitinase treatment, or by chronic antidepressant treatment. We now show that the effects of both chondroitinase and fluoxetine are mediated by the neurotrophin receptor TRKB in parvalbumin-containing (PV+) interneurons. We found that chondroitinase-induced visual cortical plasticity is dependent on TRKB in PV+ neurons. Protein tyrosine phosphatase type S (PTPσ, PTPRS), a receptor for PNNs, interacts with TRKB and inhibits its phosphorylation, and chondroitinase treatment or deletion of PTPσ increases TRKB phosphorylation. Antidepressant fluoxetine disrupts the interaction between TRKB and PTPσ, thereby increasing TRKB phosphorylation. Thus, juvenile-like plasticity induced by both chondroitinase and antidepressant treatment is mediated by TRKB activation in PV+ interneurons.

scholarly journals Molecular Mechanisms of L1 and NCAM Adhesion Molecules in Synaptic Pruning, Plasticity, and Stabilization

2021 ◽  
Vol 9 ◽  
Author(s):  
Bryce W. Duncan ◽  
Kelsey E. Murphy ◽  
Patricia F. Maness
Keyword(s):  
Adhesion Molecules ◽  
Molecular Mechanisms ◽  
Inhibitory Synapses ◽  
Mammalian Brain ◽  
Synaptic Membranes ◽  
Critical Periods ◽  
Perineuronal Net ◽  
Synaptic Regulation ◽  
Ligand Interactions ◽  
Excitatory And Inhibitory Synapses

Mammalian brain circuits are wired by dynamic formation and remodeling during development to produce a balance of excitatory and inhibitory synapses. Synaptic regulation is mediated by a complex network of proteins including immunoglobulin (Ig)- class cell adhesion molecules (CAMs), structural and signal-transducing components at the pre- and post-synaptic membranes, and the extracellular protein matrix. This review explores the current understanding of developmental synapse regulation mediated by L1 and NCAM family CAMs. Excitatory and inhibitory synapses undergo formation and remodeling through neuronal CAMs and receptor-ligand interactions. These responses result in pruning inactive dendritic spines and perisomatic contacts, or synaptic strengthening during critical periods of plasticity. Ankyrins engage neural adhesion molecules of the L1 family (L1-CAMs) to promote synaptic stability. Chondroitin sulfates, hyaluronic acid, tenascin-R, and linker proteins comprising the perineuronal net interact with L1-CAMs and NCAM, stabilizing synaptic contacts and limiting plasticity as critical periods close. Understanding neuronal adhesion signaling and synaptic targeting provides insight into normal development as well as synaptic connectivity disorders including autism, schizophrenia, and intellectual disability.

scholarly journals Critical period regulation across multiple timescales

2020 ◽  
Vol 117 (38) ◽  
pp. 23242-23251 ◽  
Author(s):  
Rebecca K. Reh ◽  
Brian G. Dias ◽  
Charles A. Nelson ◽  
Daniela Kaufer ◽  
Janet F. Werker ◽  
...  
Keyword(s):  
Critical Period ◽  
Brain Plasticity ◽  
Gamma Oscillations ◽  
Developmental Time ◽  
Brain Regions ◽  
Inhibitory Neurons ◽  
Critical Periods ◽  
Multiple Timescales ◽  
Fast Spiking ◽  
The Impact

Brain plasticity is dynamically regulated across the life span, peaking during windows of early life. Typically assessed in the physiological range of milliseconds (real time), these trajectories are also influenced on the longer timescales of developmental time (nurture) and evolutionary time (nature), which shape neural architectures that support plasticity. Properly sequenced critical periods of circuit refinement build up complex cognitive functions, such as language, from more primary modalities. Here, we consider recent progress in the biological basis of critical periods as a unifying rubric for understanding plasticity across multiple timescales. Notably, the maturation of parvalbumin-positive (PV) inhibitory neurons is pivotal. These fast-spiking cells generate gamma oscillations associated with critical period plasticity, are sensitive to circadian gene manipulation, emerge at different rates across brain regions, acquire perineuronal nets with age, and may be influenced by epigenetic factors over generations. These features provide further novel insight into the impact of early adversity and neurodevelopmental risk factors for mental disorders.

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