Repeated stimulation of cultured networks of rat cortical neurons induces parallel memory traces

Abstract

During systems consolidation, memories are spontaneously replayed favoring information transfer from hippocampus to neocortex. However, at present no empirically supported mechanism to accomplish a transfer of memory from hippocampal to extra-hippocampal sites has been offered. We used cultured neuronal networks on multielectrode arrays and small-scale computational models to study the effect of memory replay on the formation of memory traces. We show that input-deprived networks develop an activity⇔connectivity balance where dominant activity patterns support current connectivity. Electrical stimulation at one electrode disturbs this balance and induces connectivity changes. Intrinsic forces in recurrent networks lead to a new equilibrium with activity patterns that include the stimulus response. The new connectivity is no longer disrupted by this stimulus, indicating that networks memorize it. A different stimulus again induces connectivity changes upon first application but not subsequently, demonstrating the formation of a second memory trace. Returning to the first stimulus does not affect connectivity, indicating parallel storage of both traces. A computer model robustly reproduced experimental results, suggesting that spike-timing-dependent plasticity and short time depression suffice to store parallel memory traces, even in networks without particular circuitry constraints.

Maximum entropy models provide functional connectivity estimates in neural networks

“…Activity and connectivity mutually affect each other, and it has been hypothesized that networks develop an equilibrium between activity and connectivity. It requires repeated activation of patterns not included in the spontaneous activity repertoire to drive networks out of this equilibrium 4 , and the driving force applied by random stimulation is apparently insufficient to achieve this. In principle optogenetic stimulation does not directly activate inhibitory neurons, which have been described to have an important hub function in developing networks 35 .…”

“…Neuronal connectivity is essential for cognitive functions like learning and memory 1 – 3 , but is difficult to assess in the in vivo brain. Reduced models of networks of cultured neurons on micro electrode arrays have been used to investigate the relationship between connectivity and processes like memory formation 4 , 5 . Such networks present a wide range of responses to external stimuli 6 , 7 , and can produce diverse patterns from synchronous firing 8 , 9 to chaotic trajectories 10 .…”

Experimental Platform to Study Spiking Pattern Propagation in Modular Networks In Vitro

“…Such an approach induced "pathway-specific plasticity" and potentiated or depressed several neuronal connections. The results were replicated by several other laboratories with tetanus or other modified stimulation protocols [34][35][36]. Our approach, using modular networks, focuses on plasticity changes in predefined connectivity pathways grown through the microchannels.…”

Selectivity of stimulus induced responses in cultured hippocampal networks on microelectrode arrays

“…Only high-frequency stimulation significantly changed the first spike times and spike rate of the low-frequency responses (Tateno and Jimbo 1999 ; Chiappalone et al 2008 ). It was also shown that a functional structure of connectivity in the culture was affected by consequent stimulation of two electrodes (Le Feber et al 2015 ). Low-frequency electrical stimulation at one electrode disturbs the balance between activity and connectivity which induce new spiking pattern in the stimulus response.…”