Distinct Modulation of by Synaptic Potentiation in Excitatory and Inhibitory Neurons.

Selective modifications in the expression or function of dendritic ion channels regulate the propagation of synaptic inputs and determine the intrinsic excitability of a neuron. Hyperpolarization-activated cyclic nucleotide-gated (HCN) channels open upon membrane hyperpolarization and conduct a depolarizing inward current ( ). HCN channels are enriched in the dendrites of hippocampal pyramidal neurons where they regulate the integration of synaptic inputs.

Using SuperClomeleon to Measure Changes in Intracellular Chloride during Development and after Early Life Stress.

Intraneuronal chloride concentrations ([Cl]) decrease during development resulting in a shift from depolarizing to hyperpolarizing GABA responses via chloride-permeable GABA receptors. This GABA shift plays a pivotal role in postnatal brain development, and can be strongly influenced by early life experience. Here, we assessed the applicability of the recently developed fluorescent SuperClomeleon (SClm) sensor to examine changes in [Cl] using two-photon microscopy in brain slices.

Centrosome-mediated microtubule remodeling during axon formation in human iPSC-derived neurons.

Axon formation critically relies on local microtubule remodeling and marks the first step in establishing neuronal polarity. However, the function of the microtubule-organizing centrosomes during the onset of axon formation is still under debate. Here, we demonstrate that centrosomes play an essential role in controlling axon formation in human-induced pluripotent stem cell (iPSC)-derived neurons.

Reduction of Dendritic Inhibition in CA1 Pyramidal Neurons in Amyloidosis Models of Early Alzheimer's Disease.

Background: In an early stage of Alzheimer's disease (AD), before the formation of amyloid plaques, neuronal network hyperactivity has been reported in both patients and animal models. This suggests an underlying disturbance of the balance between excitation and inhibition. Several studies have highlighted the role of somatic inhibition in early AD, while less is known about dendritic inhibition.

Quantitative mapping of transcriptome and proteome dynamics during polarization of human iPSC-derived neurons.

The differentiation of neuronal stem cells into polarized neurons is a well-coordinated process which has mostly been studied in classical non-human model systems, but to what extent these findings are recapitulated in human neurons remains unclear. To study neuronal polarization in human neurons, we cultured hiPSC-derived neurons, characterized early developmental stages, measured electrophysiological responses, and systematically profiled transcriptomic and proteomic dynamics during these steps. The neuron transcriptome and proteome shows extensive remodeling, with differential expression profiles of ~1100 transcripts and ~2200 proteins during neuronal differentiation and polarization.

Network control through coordinated inhibition.

Coordinated excitatory and inhibitory activity is required for proper brain functioning. Recent computational and experimental studies have demonstrated that activity patterns in recurrent cortical networks are dominated by inhibition. Whereas previous studies have suggested that inhibitory plasticity is important for homeostatic control, this new framework puts inhibition in the driver's seat.