Abstract
The impairment of cognitive function in Alzheimer’s disease is clearly correlated to synapse loss. However, the mechanisms underlying this correlation are only poorly understood. Here, we investigate how the loss of excitatory synapses in sparsely connected random networks of spiking excitatory and inhibitory neurons alters their dynamical characteristics. Beyond the effects on the activity statistics, we find that the loss of excitatory synapses on excitatory neurons reduces the network’s sensitivity to small perturbations. This decrease in sensitivity can be considered as an indication of a reduction of computational capacity. A full recovery of the network’s dynamical characteristics and sensitivity can be achieved by firing rate homeostasis, here implemented by an up-scaling of the remaining excitatory-excitatory synapses. Mean-field analysis reveals that the stability of the linearised network dynamics is, in good approximation, uniquely determined by the firing rate, and thereby explains why firing rate homeostasis preserves not only the firing rate but also the network’s sensitivity to small perturbations.
Highlights
Accelerated synapse loss is a prominent feature in many types of neurodegenerative disorders, such as Huntington’s disease, frontotemporal dementia or Alzheimer’s disease [1,2,3,4,5]
We employ a spiking neural network model to study the effects of synaptic loss, as it is often observed in various neurodegenerative disorders, in particular Alzheimer’s disease (AD)
We show that the loss of synapses drives the network into a less sensitive regime, which potentially accounts for the cognitive deficits of AD
Summary
Accelerated synapse loss is a prominent feature in many types of neurodegenerative disorders, such as Huntington’s disease, frontotemporal dementia or Alzheimer’s disease [1,2,3,4,5]. In Alzheimer’s disease (AD), synapse loss appears to be important, as it is widespread across different brain areas and constitutes a key marker in the AD pathology (see, e.g., [5]). While the most commonly reported early symptom of AD is memory deterioration, the disease is associated with a wide range of other cognitive problems such as stereotyped, repetitive linguistic production, visuo-spatial deficits and disorientation, apraxia, and loss of executive functions, i.e. planning and abstract reasoning [20, 21]. The observed progression of cognitive symptoms goes hand in hand with brain tissue atrophy [22,23,24] associated with loss of synapses [25], suggesting that the synaptic degeneration may underlie the cognitive deterioration following the gradual involvement of different, functionally specialized brain regions
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