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The hippocampal formation is crucial for learning and memory, with submodule CA3 thought to be the substrate of pattern completion. However, the underlying synaptic and computational mechanisms of this network are not well understood. Here, we perform circuit reconstruction of a CA3 module using three dimensional (3D) electron microscopy data and combine this with functional connectivity recordings and computational simulations to determine possible CA3 network mechanisms. Direct measurements of connectivity schemes with both physiological measurements and structural 3D EM revealed a high connectivity rate, multi-fold higher than previously assumed. Mathematical modelling indicated that such CA3 networks can robustly generate pattern completion and replay memory sequences. In conclusion, our data demonstrate that the connectivity scheme of the hippocampal submodule is well suited for efficient memory storage and retrieval. [ABSTRACT FROM AUTHOR]

The article focuses on the biophysical properties of voltage-gated sodium (Na+) and potassium (K+) channels in human and mouse pyramidal neurons and their impact on the stability of action potentials (APs) during sustained firing. Human pyramidal neurons exhibit stable and fast AP kinetics, attributed to more depolarized voltage dependence, slower inactivation, and faster recovery from inactivation of Na+ channels, as well as right-shifted activation and inactivation curves of K+ channels.

The article focuses on understanding the mechanisms underlying fast cortical signaling in human fast-spiking interneurons (FSINs). The study compares human and mouse FSINs, revealing that despite elongated dendrites in human FSINs, they maintain fast inhibition through adaptations such as stronger excitatory inputs, larger dendrite diameter with reduced complexity, faster action potential initiation, and faster and larger inhibitory output.

The hippocampal formation is crucial for learning and memory, with submodule CA3 thought to be the substrate of pattern completion. However, the underlying synaptic and computational mechanisms of this network are not well understood. Here, we perform circuit reconstruction of a CA3 module using three dimensional (3D) electron microscopy data and combine this with functional connectivity recordings and computational simulations to determine possible CA3 network mechanisms. Direct measurements of connectivity schemes with both physiological measurements and structural 3D EM revealed a high connectivity rate, multi-fold higher than previously assumed. Mathematical modelling indicated that such CA3 networks can robustly generate pattern completion and replay memory sequences. In conclusion, our data demonstrate that the connectivity scheme of the hippocampal submodule is well suited for efficient memory storage and retrieval., Competing Interests: Competing interests statement:The authors declare no competing interest.

Human cortical pyramidal neurons are large, have extensive dendritic trees, and yet have unexpectedly fast input-output properties: Rapid subthreshold synaptic membrane potential changes are reliably encoded in timing of action potentials (APs). Here, we tested whether biophysical properties of voltage-gated sodium (Na + ) and potassium (K + ) currents in human pyramidal neurons can explain their fast input-output properties. Human Na + and K + currents exhibited more depolarized voltage dependence, slower inactivation, and faster recovery from inactivation compared with their mouse counterparts. Computational modeling showed that despite lower Na + channel densities in human neurons, the biophysical properties of Na + channels resulted in higher channel availability and contributed to fast AP kinetics stability. Last, human Na + channel properties also resulted in a larger dynamic range for encoding of subthreshold membrane potential changes. Thus, biophysical adaptations of voltage-gated Na + and K + channels enable fast input-output properties of large human pyramidal neurons.