Signature morpho-electric, transcriptomic, and dendritic properties of human layer 5 neocortical pyramidal neurons

Resilience through diversity: Loss of neuronal heterogeneity in epileptogenic human tissue impairs network resilience to sudden changes in synchrony

“…Additionally, we obtained, from patients with mesial temporal sclerosis, recordings from neurons in non-epileptogenic middle temporal gyrus (MTG), which is the overlying cortex routinely removed to approach deep temporal structures. The MTG is a well-characterized part of the human brain, representing a common anatomical region from which non-epileptogenic brain tissue has been studied electrophysiologically and transcriptomically (Hodge et al, 2019; Moradi Chameh et al, 2021; Beaulieu-Laroche et al, 2018; Kalmbach et al, 2021), and thus our primary source of non-epileptogenic neurons. We note that each of these studies classify these neurons as indicative of “seemingly normal” human neurons independent of the patients’ epilepsy or tumor diagnoses (i.e., a best case control given limitations in obtaining human tissue).…”

“…Tissue from non-epileptogenic frontal lobe obtained during tumor resection was obtained from two patients, ages 37 and 58 years, with 8 and 4 cells studied per patient, and was also considered "healthy, non-epileptogenic" tissue as it was taken away from the tumor itself. This tissue is a common source of human cortical tissue to study human cell and circuit properties (Kalmbach et al, 2018(Kalmbach et al, , 2021Testa-Silva et al, 2014).…”

Age-dependent increased sag amplitude in human pyramidal neurons dampens baseline cortical activity

“…We used reconstructed human neuron morphologies from ABI for the L5 Pyr neuron (Neuron ID: 562381210; donor age = 34 years) and the PV interneuron. The L5 pyramidal neuron morphology that we chose was a typical intra-telencephalic-projecting (IT)-like, which is the most abundant Pyr neuron type in human cortical layer 5 (Kalmbach et al, 2021;.…”

Unraveling Brain Microcircuits, Dendritic Spines, and Synaptic Processing Using Multiple Complementary Approaches

“…The impact of heterogeneous glial cells and the role of the extracellular matrix in tetrapartite synapses need to be addressed (Chelini et al, 2018 ; Mederos et al, 2018 ; Tønnesen et al, 2018 ; Nguyen et al, 2020 ; Klimczak et al, 2021 ). The elucidation of the evolutionary reason for the divergence in gene expression patterns in the cerebral cortex, and the features that determine neuronal diversity and specialization in humans are important (Hodge et al, 2019 , 2020 ; Kalmbach et al, 2021 ). Regarding the latter, some features of human cortical pyramidal neurons include: (1) larger dendritic length and branch complexity than macaque and mice (Mohan et al, 2015 ; Benavides-Piccione et al, 2020 ); (2) a class of calcium-mediated graded dendritic action potentials that would classify linearly non-separable inputs (Gidon et al, 2020 ); and (3) membrane properties that significantly enhance synaptic charge-transfer from dendrites to soma and spike propagation along the axon (Eyal et al, 2016 ).…”