Morpho-electric and computational properties of three types of human hippocampal CA1 pyramidal neurons

Abstract

Hippocampal pyramidal neuron activity underlies episodic memory and spatial navigation. Although extensively studied in rodents, extremely little is known about human hippocampal pyramidal neurons, even though human hippocampus underwent strong evolutionary reorganization and shows lower theta rhythm frequencies. To test whether biophysical and computational properties of humanCA1pyramidal neurons can explain observed rhythms, we map the morpho-electric and computational properties of individualCA1pyramidal neurons in human, non-pathological hippocampal slices from neurosurgery. HumanCA1pyramidal neurons have extensive dendrites and resonate at 2.9 Hz, optimally tuned to human theta frequencies. Morphological and biophysical properties reveal three cell types with distinct dendrite bifurcations and physiology. Data-driven biophysical models show that humanCA1pyramidal neurons use i) computationally independent dendritic compartments, ii) preferential routing of electrical activity towards soma or dendritic tree and iii) non-linear input-output transformations. Across cell types, morpho-electric properties consistently increase computational richness in humanCA1pyramidal neurons.TeaserHumanCA1pyramidal neurons have large and intricate morphologies, which translates to complex computational properties.

A biologically inspired repair mechanism for neuronal reconstructions with a focus on human dendrites

“…Additionally, since pyramidal neuron main apical dendrites can branch, as observed in Refs . [ 26 ] and [ 31 ] there is a main growth option for the conserved growth mode (see Methods ). With this option, a prominent straight main apical dendrite is grown first and then oblique dendrites are added.…”

“…The dendritic spanning fields of these artificially repaired morphologies are based on the layer limitation boundaries marked out in the slice image. Furthermore, it was assumed that CA1 pyramidal cell dendrites would extend more than halfway into the SLM when the soma of the neuron is close to the SP-SR boundary, in order to make synaptic connections with axons from the perforant pathway [ 31 , 63 ]. S2 Fig shows examples of regions where dendrites were missing from the neuron reconstructions.…”

“…The maximum distance an incomplete end can have to V depends on the size of the original input tree. Additionally, the noninvasive/conserved growth mode has an option (main growth) specifically designed for severed apical dendrites of pyramidal neurons, since they usually feature one or more prominent main apical dendrites [ 26 , 31 ]. These grow approximately in a straight line from the root of the tree.…”

“…Such incomplete reconstructions, further limit the ability to study dendritic anatomy. However, the characterisation of morphological differences between human and other species’ neural circuits [ 26 , 29 – 31 ] is of great importance, since they have been shown to lead to distinct computational properties [ 11 , 32 – 34 ]. Therefore, more complete human morphologies are urgently needed for a better understanding of human neuronal physiology and pathophysiology and for the creation of realistic computational models of human dendrites [ 5 , 13 , 15 , 35 ].…”