Synaptic Failure Differentially Affects Pattern Formation in Heterogenous Networks

Abstract

The communication of neurons is primarily maintained by synapses, which play a crucial role in the functioning of the nervous system. Therefore, synaptic failure may critically impair information processing in the brain and may underlie many neurodegenerative diseases. A number of studies have suggested that synaptic failure may preferentially target neurons with high connectivity (i.e., network hubs). As a result, the activity of these highly connected neurons can be significantly affected. It has been speculated that anesthetics regulate conscious state by affecting synaptic transmission at these network hubs and subsequently reducing overall coherence in the network activity. In addition, hubs in cortical networks are shown to be more vulnerable to amyloid deposition because of their higher activity within the network, causing decrease in coherence patterns and eventually Alzheimer’s disease (AD). Here, we investigate how synaptic failure can affect spatio-temporal dynamics of scale free networks, having a power law scaling of number of connections per neuron – a relatively few neurons (hubs) with a lot of emanating or incoming connections and many cells with low connectivity. We studied two types of synaptic failure: activity-independent and targeted, activity-dependent synaptic failure. We defined scale-free network structures based on the dominating direction of the connections at the hub neurons: incoming and outgoing. We found that the two structures have significantly different dynamical properties. We show that synaptic failure may not only lead to the loss of coherence but unintuitively also can facilitate its emergence. We show that this is because activity-dependent synaptic failure homogenizes the activity levels in the network creating a dynamical substrate for the observed coherence increase. Obtained results may lead to better understanding of changes in large-scale pattern formation during progression of neuro-degenerative diseases targeting synaptic transmission.

Acrolein, an endogenous aldehyde induces synaptic dysfunction in vitro and in vivo: Involvement of RhoA/ROCK2 pathway

“…At the MCI stage, there is no obvious organic disease in the brain of AD patients, and the decline in cognitive level may be caused by abnormal synaptic function. Impairment of synapse function occurs before synapse loss and neuronal degeneration (Budak & Zochowski, 2019 ). Therefore, research on synaptic damage is particularly critical for the treatment of early AD (Jackson et al, 2019 ).…”

Digging Deeper: Advancements in Visualization of Inhibitory Synapses in Neurodegenerative Disorders

“…In the adult brain, GABAergic neurons are the major inhibitory neurons that are critical to maintaining synaptic balance [5]. Any loophole in inhibitory synaptic plasticity can trigger accidents in neuronal communication, leading to progressive neurodegenerative diseases [8,9]. in ND, with emphasis on Alzheimer's disease, and discuss the established and evolving methods of visualization that have contributed to our knowledge of changes in inhibitory synapse plasticity so far.…”

“…In the adult brain, GABAergic neurons are the major inhibitory neurons that are critical to maintaining synaptic balance [5]. Any loophole in inhibitory synaptic plasticity can trigger accidents in neuronal communication, leading to progressive neurodegenerative diseases [8,9]. AD is characterized by memory loss and cognitive impairment, which is linked to the loss of inhibitory synapses in the brain [22].…”