The information processing abilities of neural circuits arise from their synaptic connection patterns. Understanding the laws governing these connectivity patterns is essential for understanding brain function. The overall distribution of synaptic strengths of local excitatory connections in cortex and hippocampus is long-tailed, exhibiting a small number of synaptic connections of very large efficacy. At the same time, new synaptic connections are constantly being created and individual synaptic connection strengths show substantial fluctuations across time. It remains unclear through what mechanisms these properties of neural circuits arise and how they contribute to learning and memory. In this study we show that fundamental characteristics of excitatory synaptic connections in cortex and hippocampus can be explained as a consequence of self-organization in a recurrent network combining spike-timing-dependent plasticity (STDP), structural plasticity and different forms of homeostatic plasticity. In the network, associative synaptic plasticity in the form of STDP induces a rich-get-richer dynamics among synapses, while homeostatic mechanisms induce competition. Under distinctly different initial conditions, the ensuing self-organization produces long-tailed synaptic strength distributions matching experimental findings. We show that this self-organization can take place with a purely additive STDP mechanism and that multiplicative weight dynamics emerge as a consequence of network interactions. The observed patterns of fluctuation of synaptic strengths, including elimination and generation of synaptic connections and long-term persistence of strong connections, are consistent with the dynamics of dendritic spines found in rat hippocampus. Beyond this, the model predicts an approximately power-law scaling of the lifetimes of newly established synaptic connection strengths during development. Our results suggest that the combined action of multiple forms of neuronal plasticity plays an essential role in the formation and maintenance of cortical circuits.

Biological neural networks are shaped by a large number of plasticity mechanisms operating at different time scales. How these mechanisms work together to sculpt such networks into effective information processing circuits is still poorly understood. Here we study the spontaneous development of synfire chains in a self-organizing recurrent neural network (SORN) model that combines a number of different plasticity mechanisms including spike-timing-dependent plasticity, structural plasticity, as well as homeostatic forms of plasticity. We find that the network develops an abundance of feed-forward motifs giving rise to synfire chains. The chains develop into ring-like structures, which we refer to as “synfire rings.” These rings emerge spontaneously in the SORN network and allow for stable propagation of activity on a fast time scale. A single network can contain multiple non-overlapping rings suppressing each other. On a slower time scale activity switches from one synfire ring to another maintaining firing rate homeostasis. Overall, our results show how the interaction of multiple plasticity mechanisms might give rise to the robust formation of synfire chains in biological neural networks.

Abnormal gamma band power across cortex and striatum is an important phenotype of Huntington’s disease (HD) in both patients and animal models, but neither the origin nor the functional relevance of this phenotype is well understood. Here, we analyzed local field potential (LFP) activity in freely behaving, symptomatic R6/2 and Q175 mouse models and corresponding wild-type (WT) controls. We focused on periods of quiet rest, which show strong γ activity in HD mice. Simultaneous recording from motor cortex and its target area in dorsal striatum in the R6/2 model revealed exaggerated functional coupling over that observed in WT between the phase of delta frequencies (1–4 Hz) in cortex and striatum and striatal amplitude modulation of low γ frequencies (25–55 Hz; i.e., phase-amplitude coupling, PAC), but no evidence that abnormal cortical activity alone can account for the increase in striatal γ power. Both HD mouse models had stronger coupling of γ amplitude to δ phase and more unimodal phase distributions than their WT counterparts. To assess the possible role of striatal fast-spiking interneurons (FSIs) in these phenomena, we developed a computational model based on additional striatal recordings from Q175 mice. Changes in peak γ frequency and power ratio were readily reproduced by our computational model, accounting for several experimental findings reported in the literature. Our results suggest that HD is characterized by both a reorganization of cortico-striatal drive and specific population changes related to intrastriatal synaptic coupling.

We present a network model of striatum, which generates “winnerless” dynamics typical for a network of sparse, unidirectionally connected inhibitory units. We observe that these dynamics, while interesting and a good match to normal striatal electrophysiological recordings, are fragile. Specifically, we find that randomly initialized networks often show dynamics more resembling “winner-take-all,” and relate this “unhealthy” model activity to dysfunctional physiological and anatomical phenotypes in the striatum of Huntington's disease animal models. We report plasticity as a potent mechanism to refine randomly initialized networks and create a healthy winnerless dynamic in our model, and we explore perturbations to a healthy network, modeled on changes observed in Huntington's disease, such as neuron cell death and increased bidirectional connectivity. We report the effect of these perturbations on the conversion risk of the network to an unhealthy state. Finally we discuss the relationship between structural and functional phenotypes observed at the level of simulated network dynamics as a promising means to model disease progression in different patient populations.

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