Recent imaging studies suggest that object knowledge is stored in the brain as a distributed network of many cortical areas. Motivated by these observations, we study a multimodular associative memory network, whose functional goal is to store patterns with different coding levels--patterns that vary in the number of modules in which they are encoded. We show that in order to accomplish this task, synaptic inputs should be segregated into intramodular projections and intermodular projections, with the latter undergoing additional nonlinear dendritic processing. This segregation makes sense anatomically if the intermodular projections represent distal synaptic connections on apical dendrites. It is then straightforward to show that memories encoded in more modules are more resilient to focal afferent damage. Further hierarchical segregation of intermodular connections on the dendritic tree improves this resilience, allowing memory retrieval from input to just one of the modules in which it is encoded.

Since their conception half a century ago, Hebbian cell assemblies have become a basic term in the neurosciences, and the idea that learning takes place through synaptic modifications has been accepted as a fundamental paradigm. As synapses undergo continuous metabolic turnover, adopting the stance that memories are engraved in the synaptic matrix raises a fundamental problem: How can memories be maintained for very long time periods? We present a novel solution to this long-standing question, based on biological evidence of neuronal regulation mechanisms that act to maintain neuronal activity. Our mechanism is developed within the framework of a neural model of associative memory. It is operative in conjunction with random activation of the memory system and is able to counterbalance degradation of synaptic weights and normalize the basins of attraction of all memories. Over long time periods, when the variance of the degradation process becomes important, the memory system stabilizes if its synapses are appropriately bounded. Thus, the remnant memory system is obtained by a dynamic process of synaptic selection and growth driven by neuronal regulatory mechanisms. Our model is a specific realization of dynamic stabilization of neural circuitry, which is often assumed to take place during sleep.

In the framework of an associative memory model, we study the interplay between synaptic deletion and compensation, and memory deterioration, a clinical hallmark of Alzheimer's disease. Our study is motivated by experimental evidence that there are regulatory mechanisms that take part in the homeostasis of neuronal activity and act on the neuronal level. We show that following synaptic deletion, synaptic compensation can be carried out efficiently by a local, dynamic mechanism, where each neuron maintains the profile of its incoming post-synaptic current. Our results open up the possibility that the primary factor in the pathogenesis of cognitive deficiencies in Alzheimer's disease (AD) is the failure of local neuronal regulatory mechanisms. Allowing for neuronal death, we observe two pathological routes in AD, leading to different correlations between the levels of structural damage and functional decline.