Robust Resting-State Dynamics in a Large-Scale Spiking Neural Network Model of Area CA3 in the Mouse Hippocampus

Hippocampal area CA3 performs the critical auto-associative function underlying pattern completion in episodic memory. Without external inputs, the electrical activity of this neural circuit reflects the spontaneous spiking interplay among glutamatergic Pyramidal neurons and GABAergic interneurons. However, the network mechanisms underlying these resting-state firing patterns are poorly understood. Leveraging the Hippocampome.org knowledge base, we developed a data-driven, large-scale spiking neural network (SNN) model of mouse CA3 with 8 neuron types, 90,000 neurons, 51 neuron-type specific connections, and 250,000,000 synapses. We instantiated the SNN in the CARLsim4 multi-GPU simulation environment using the Izhikevich and Tsodyks-Markram formalisms for neuronal and synaptic dynamics, respectively. We analyzed the resultant population activity upon transient activation. The SNN settled into stable oscillations with a biologically plausible grand-average firing frequency, which was robust relative to a wide range of transient activation. The diverse firing patterns of individual neuron types were consistent with existing knowledge of cell type-specific activity in vivo. Altered network structures that lacked neuron- or connection-type specificity were neither stable nor robust, highlighting the importance of neuron type circuitry. Additionally, external inputs reflecting dentate mossy fibers shifted the observed rhythms to the gamma band. We freely released the CARLsim4-Hippocampome framework on GitHub to test hippocampal hypotheses. Our SNN may be useful to investigate the circuit mechanisms underlying the computational functions of CA3. Moreover, our approach can be scaled to the whole hippocampal formation, which may contribute to elucidating how the unique neuronal architecture of this system subserves its crucial cognitive roles.

Automated summary

The hippocampal area CA3 plays a critical role in pattern completion in episodic memory, but the network mechanisms underlying the resting-state firing patterns are poorly understood. In this study, a large-scale spiking neural network model of mouse CA3 was developed, which exhibited stable oscillations with biologically plausible firing frequencies. The firing patterns of individual neuron types were consistent with existing knowledge of cell type-specific activity. Importantly, altered network structures lacking neuron or connection specificity were neither stable nor robust. This research contributes to our understanding of the circuit mechanisms underlying the computational functions of CA3.