Local Connectivity and Synaptic Dynamics in Mouse and Human Neocortex

Abstract

We present a unique, extensive, public synaptic physiology dataset. The dataset contains over 20,000 neuron pairs probed with multipatch using standardized protocols to capture short-term dynamics. Recordings were made in the human temporal cortex and the adult mouse visual cortex. Our main purpose is to offer data and analyses that provide a more complete picture of the cortical microcircuit to the community. We also make several important findings that relate connectivity and synaptic properties to the major cell subclasses and cortical layer via the development of novel analysis methods for quantifying connectivity, synapse properties, and synaptic dynamics. We find that excitatory synaptic dynamics depend strongly on the postsynaptic cell subclass, whereas inhibitory synaptic dynamics depend on the presynaptic cell subclass. Despite these associations, short-term synaptic plasticity is heterogeneous in most subclass to subclass connections. We also find that intralaminar connection probability exhibits a strong layer dependence. In human cortex, we find that excitatory synapses are highly reliable, recover rapidly, and are distinct from mouse excitatory synapses.

Cortical Cartography: Mapping Arealization Using Single-Cell Omics Technology

“…Consistent with these observations, recent comprehensive work has shown that while gene expression can be correlated to a cell's electrophysiology and morphology, each additional parameter adds slightly more nuanced variation (Nandi et al, 2020;Haghighi et al, 2021). As tools emerge to interrogate individual cell connectivity and merge them with neuronal subtypes defined in other contexts, heterogeneity has been identified within "subclasses" (Campagnola et al, 2021). These findings highlight gaps in our understanding of the complete set of properties that define how a cell functions.…”

Strong and specific connections between retinal axon mosaics and midbrain neurons revealed by large scale paired recordings

“…Across the population, we discovered a log-normal distribution of connection and coupling strengths. Log-normal distributions of connection strength are widely observed in the vertebrate brain (Buzsáki and Mizuseki, 2014; Cossell et al, 2015; Jouhanneau et al, 2015, 2018), including human (Campagnola et al, 2021), which could be the result of circuit refinement during development (Dhande et al, 2011) by which only a few strong connections remain after the refinement process. Our data support this view whereby RGCs establish only one or a few strong connections with SC neurons and multiple weaker connections (Figures 4E/F and S6E).…”

Somatic HCN channels augment and speed up GABAergic basket cell input-output function in human neocortex

“…The somatic membrane time-constant is a key determinant of the input-output relation of neurons and it determines how rapidly a neuron responds to an excitatory stimulus 52 . In the human neocortex, unitary pyramidal cells form powerful excitatory connections on local pv+BCs, in order to generate suprathreshold EPSPs at the interneuron resting potential by unitary spike 10, 14, 15, 21 . In this input-to-output signaling, the pv+BC’s firing delay to the large EPSC is couple of milliseconds 10, 12, 21 54 .…”

“…In the human neocortex, unitary pyramidal cells form powerful excitatory connections on local pv+BCs, in order to generate suprathreshold EPSPs at the interneuron resting potential by unitary spike 10, 14, 15, 21 . In this input-to-output signaling, the pv+BC’s firing delay to the large EPSC is couple of milliseconds 10, 12, 21 54 . In the rapid EPSP-spike transformation, the somatic G HCN at Em is highly relevant, considering that HCN-channel conductance remains practically unchanged during fast Vm shifts such as EPSP rise and the EPSP-spike coupling.…”

“…Understanding the functioning of human neurons is highly relevant, because findings in experimental animals do not always translate to human. In fact, analogous neuronal types between the human and rodent cortex exhibit various between-species differences in their physiological functional parameters 9, 13, 14, 15, 16, 17, 18, 19, 20, 21 . Species-specific behaviors may hence arise from even small differences in neuronal types and neuronal circuits 22, 23 , making it critical to uncover the “uniqueness” of the human neurons and to investigate its outcome on the operation of anatomically identified neuronal circuits.…”