scholarly journals Proteolytic Remodeling of Perineuronal Nets: Effects on Synaptic Plasticity and Neuronal Population Dynamics

2018 ◽  
Vol 2018 ◽  
pp. 1-13 ◽  
Author(s):  
P. Lorenzo Bozzelli ◽  
Seham Alaiyed ◽  
Eunyoung Kim ◽  
Sonia Villapol ◽  
Katherine Conant

The perineuronal net (PNN) represents a lattice-like structure that is prominently expressed along the soma and proximal dendrites of parvalbumin- (PV-) positive interneurons in varied brain regions including the cortex and hippocampus. It is thus apposed to sites at which PV neurons receive synaptic input. Emerging evidence suggests that changes in PNN integrity may affect glutamatergic input to PV interneurons, a population that is critical for the expression of synchronous neuronal population discharges that occur with gamma oscillations and sharp-wave ripples. The present review is focused on the composition of PNNs, posttranslation modulation of PNN components by sulfation and proteolysis, PNN alterations in disease, and potential effects of PNN remodeling on neuronal plasticity at the single-cell and population level.

2020 ◽  
Vol 323 ◽  
pp. 113077 ◽  
Author(s):  
P. Lorenzo Bozzelli ◽  
Adam Caccavano ◽  
Valeria Avdoshina ◽  
Italo Mocchetti ◽  
Jian-Young Wu ◽  
...  

2021 ◽  
Author(s):  
Jane Morphett ◽  
◽  
Alexandra Whittaker ◽  
Amy Reichelt ◽  
Mark Hutchinson

Is the perineuronal net structure within emotional processing brain regions associated with changes in affective state? The objective of this scoping review is to bring together the literature on human and animal studies which have measured perineuronal net structure in brain regions associated with emotional processing (such as but not limited to amygdala, hippocampus and prefrontal cortex). Perineuronal nets are a specialised form of condensed extracellular matrix that enwrap and protect neurons (Suttkus et al., 2016), regulate synaptic plasticity (Celio and Blumcke, 1994) and ion homeostasis (Morawski et al., 2015). Perineuronal nets are dynamic structures that are influenced by external and internal environmental shifts – for example, increasing in intensity and number in response to stressors (Blanco and Conant, 2021) and pharmacological agents (Riga et al., 2017). This review’s objective is to generate a compilation of existing knowledge regarding the structural changes of perineuronal nets in experimental studies that manipulate affective state, including those that alter environmental stressors. The outcomes will inform future research directions by elucidating non-cellular central nervous system mechanisms that underpin positive and negative emotional states. These methods may also be targets for manipulation to manage conditions of depression or promote wellbeing. Population: human and animal Condition: affective state as determined through validated behavioural assessment methods or established biomarkers. This includes both positive and negative affective states. Context: PNN structure, measuringPNNs.


2021 ◽  
Vol 13 ◽  
Author(s):  
Jereme C. Wingert ◽  
Barbara A. Sorg

Perineuronal nets (PNNs) are specialized extracellular matrix structures that surround specific neurons in the brain and spinal cord, appear during critical periods of development, and restrict plasticity during adulthood. Removal of PNNs can reinstate juvenile-like plasticity or, in cases of PNN removal during early developmental stages, PNN removal extends the critical plasticity period. PNNs surround mainly parvalbumin (PV)-containing, fast-spiking GABAergic interneurons in several brain regions. These inhibitory interneurons profoundly inhibit the network of surrounding neurons via their elaborate contacts with local pyramidal neurons, and they are key contributors to gamma oscillations generated across several brain regions. Among other functions, these gamma oscillations regulate plasticity associated with learning, decision making, attention, cognitive flexibility, and working memory. The detailed mechanisms by which PNN removal increases plasticity are only beginning to be understood. Here, we review the impact of PNN removal on several electrophysiological features of their underlying PV interneurons and nearby pyramidal neurons, including changes in intrinsic and synaptic membrane properties, brain oscillations, and how these changes may alter the integration of memory-related information. Additionally, we review how PNN removal affects plasticity-associated phenomena such as long-term potentiation (LTP), long-term depression (LTD), and paired-pulse ratio (PPR). The results are discussed in the context of the role of PV interneurons in circuit function and how PNN removal alters this function.


Cells ◽  
2021 ◽  
Vol 10 (8) ◽  
pp. 2021
Author(s):  
Dominika Drulis-Fajdasz ◽  
Kinga Gostomska-Pampuch ◽  
Przemysław Duda ◽  
Jacek Roman Wiśniewski ◽  
Dariusz Rakus

Aging is associated with a general decline in cognitive functions, which appears to be due to alterations in the amounts of proteins involved in the regulation of synaptic plasticity. Here, we present a quantitative analysis of proteins involved in neurotransmission in three brain regions, namely, the hippocampus, the cerebral cortex and the cerebellum, in mice aged 1 and 22 months, using the total protein approach technique. We demonstrate that although the titer of some proteins involved in neurotransmission and synaptic plasticity is affected by aging in a similar manner in all the studied brain formations, in fact, each of the formations represents its own mode of aging. Generally, the hippocampal and cortical proteomes are much more unstable during the lifetime than the cerebellar proteome. The data presented here provide a general picture of the effect of physiological aging on synaptic plasticity and might suggest potential drug targets for anti-aging therapies.


2019 ◽  
Vol 20 (17) ◽  
pp. 4108 ◽  
Author(s):  
Mateusz Bosiacki ◽  
Magdalena Gąssowska-Dobrowolska ◽  
Klaudyna Kojder ◽  
Marta Fabiańska ◽  
Dariusz Jeżewski ◽  
...  

Extracellular matrix (ECM) molecules that are released by neurons and glial cells form perineuronal nets (PNNs) and modulate many neuronal and glial functions. PNNs, whose structure is still not known in detail, surround cell bodies and dendrites, which leaves free space for synapses to come into contact. A reduction in the expression of many neuronal ECM components adversely affects processes that are associated with synaptic plasticity, learning, and memory. At the same time, increased ECM activity, e.g., as a result of astrogliosis following brain damage or in neuroinflammation, can also have harmful consequences. The therapeutic use of enzymes to attenuate elevated neuronal ECM expression after injury or in Alzheimer’s disease has proven to be beneficial by promoting axon growth and increasing synaptic plasticity. Yet, severe impairment of ECM function can also lead to neurodegeneration. Thus, it appears that to ensure healthy neuronal function a delicate balance of ECM components must be maintained. In this paper we review the structure of PNNs and their components, such as hyaluronan, proteoglycans, core proteins, chondroitin sulphate proteoglycans, tenascins, and Hapln proteins. We also characterize the role of ECM in the functioning of the blood-brain barrier, neuronal communication, as well as the participation of PNNs in synaptic plasticity and some clinical aspects of perineuronal net impairment. Furthermore, we discuss the participation of PNNs in brain signaling. Understanding the molecular foundations of the ways that PNNs participate in brain signaling and synaptic plasticity, as well as how they change in physiological and pathological conditions, may help in the development of new therapies for many degenerative and inflammatory diseases of the brain.


2019 ◽  
Author(s):  
John P McClure ◽  
Pierre-Olivier Polack

Multimodal sensory integration facilitates the generation of a unified and coherent perception of the environment. It is now well established that unimodal sensory perceptions, such as vision, are improved in multisensory contexts. While multimodal integration is primarily performed by dedicated multisensory brain regions such as the association cortices or the superior colliculus, recent studies have shown that multisensory interactions also occur in primary sensory cortices. In particular, sounds were shown to modulate the responses of neurons located in layers 2/3 (L2/3) of the mouse primary visual cortex (V1). Yet, the net effect of sound modulation at the V1 population level remained unclear. Here, we performed two-photon calcium imaging in awake mice to compare the representation of the orientation and the direction of drifting gratings by V1 L2/3 neurons in unimodal (visual only) or multi-modal (audiovisual) conditions. We found that sound modulation depended on the tuning properties (orientation and direction selectivity) and response amplitudes of V1 L2/3 neurons. Sounds potentiated the responses of neurons that were highly tuned to the cue orientation and direction but weakly active in the unimodal context, following the principle of inverse effectiveness of multimodal integration. Moreover, sound suppressed the responses of neurons untuned for the orientation and/or the direction of the visual cue. Altogether, sound modulation improved the representation of the orientation and direction of the visual stimulus in V1 L2/3. Namely, visual stimuli presented with auditory stimuli recruited a neuronal population better tuned to the visual stimulus orientation and direction than when presented alone.


2012 ◽  
Vol 279 (1746) ◽  
pp. 4505-4512 ◽  
Author(s):  
Hannah J. Tidbury ◽  
Alex Best ◽  
Mike Boots

Exposure to low doses of pathogens that do not result in the host becoming infectious may ‘prime’ the immune response and increase protection to subsequent challenge. There is increasing evidence that such immune priming is a widespread and important feature of invertebrate host–pathogen interactions. Immune priming clearly has implications for individual hosts but will also have population-level implications. We present a susceptible–primed–infectious model—in contrast to the classic susceptible–infectious–recovered framework—to investigate the impacts of immune priming on pathogen persistence and population stability. We describe impacts of immune priming on the epidemiology of the disease in both constant and seasonal environments. A key result is that immune priming may act to destabilize population dynamics. In particular, when the proportion of individuals becoming primed rather than infected is high, but this priming does not confer full immunity, the population may be strongly destabilized through the generation of limit cycles. We discuss the implications of our model both in the context of invertebrate immunity and more widely.


eLife ◽  
2015 ◽  
Vol 4 ◽  
Author(s):  
Yunlei Yang ◽  
Peter Lee ◽  
Scott M Sternson

N-Methyl-D-aspartate receptors (NMDA-Rs) are ion channels that are important for synaptic plasticity, which is involved in learning and drug addiction. We show enzymatic targeting of an NMDA-R antagonist, MK801, to a molecularly defined neuronal population with the cell-type-selectivity of genetic methods and the temporal control of pharmacology. We find that NMDA-Rs on dopamine neurons are necessary for cocaine-induced synaptic potentiation, demonstrating that cell type-specific pharmacology can be used to dissect signaling pathways within complex brain circuits.


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