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Leibner, Y.

Publications and source records attributed to Leibner, Y..

3 recordsLinked to original sources

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

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 human CA1 pyramidal neurons can explain observed rhythms, we map the morpho-electric and computational properties of individual CA1 pyramidal neurons in human, non-pathological hippocampal slices from neurosurgery. Human CA1 pyramidal 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 human CA1 pyramidal 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 human CA1 pyramidal neurons. TeaserHuman CA1 pyramidal neurons have large and intricate morphologies, which translates to complex computational properties.

neuroscience↗

Accelerated signal propagation speed in human neocortical microcircuits

Human-specific cognitive abilities depend on information processing in the cerebral cortex, where the neurons are significantly larger and their processes longer and sparser compared to rodents. We found that, in synaptically connected layer 2/3 pyramidal cells (L2/3 PCs), the delay in signal propagation from soma to soma is similar in humans and rodents. To compensate for the longer processes of neurons, membrane potential changes in human axons and/or dendrites must propagate faster. Dual somato-dendritic and somato-axonal patch recordings show that the propagation speed of action potentials (APs) is similar in human and rat axons, but the forward propagation of excitatory postsynaptic potentials (EPSPs) and the backward propagation of APs are 26 and 47% faster in human dendrites, respectively. Accurate biophysical models of human and rat L2/3 PCs, combined with pharmacological manipulations of membrane properties, have shown that various factors enhance EPSP propagation in humans; the key factor is the large conductance load imposed by the large basal dendritic tree in humans, the key factor responsible for the accelerated signal propagation in human cortical dendrites. Larger dendritic diameter in humans as well as differences in cable and ion channel properties, also contribute to the enhancement of signal propagation in human L2/3 dendrites.

neuroscience↗

Nonlinear relationship between multimodal adrenergic responses and local dendritic activity in primary sensory cortices

The axonal projections of the adrenergic system to the neocortex, originating from the locus coeruleus (LC), form a dense network. These axons release the neuromodulator norepinephrine (NE) which is involved in many cognitive functions such as attention, arousal, and working memory. Using two-photon Ca2+ imaging of NE axons in the cortex of awake mice, we investigated what drives their phasic activity. We discovered that NE axons in the primary somatosensory cortex responded robustly and reliably to somatosensory stimulation. Surprisingly, the same axons also responded to stimuli of other modalities (auditory and visual). Similar responses to all three modalities were observed in the primary visual cortex as well. These results indicate that phasic responses of NE axons to sensory stimuli provide a robust multimodal signal. However, despite the robustness, we also noticed consistent variations in the data. For example, responses to whisker stimulations were larger than to auditory and visual stimulations in both the barrel and the visual cortices. To test whether the variations in NE axonal responses can carry behaviorally meaningful information, we trained mice in an associative auditory fear conditioning paradigm. We found that following conditioning the response of NE axons increased only for CS+, namely the signal undergoes experience-dependent plasticity and is specific to meaningful sounds. To test if variations in NE axonal responses can differentially affect the cortical microcircuit, we used dual-color two-photon Ca2+ imaging and studied the relationship between the activity of NE axons and local dendrites. We found dendritic Ca2+ signals in barrel cortex in response to auditory stimuli, but these responses were variable and unreliable. Strikingly, the probability of such dendritic signals increased nonlinearly with the Ca2+ signals of NE axons. Our results demonstrate that the phasic activity of the noradrenergic neurons may serve as a robust multimodal and plastic signal in sensory cortices. Furthermore, the variations in the NE axonal activity carry behaviorally meaningful signals and can predict the probability of local dendritic Ca2+ events.

neuroscience↗