Select neuronal populations display steady rhythmic neuronal firing that provides tonic excitation to drive downstream networks and behaviors. In noradrenergic neurons of the locus coeruleus (LC), circadian neurons of the suprachiasmatic nucleus (SCN), and CO2/H+-activated neurons of the brainstem retrotrapezoid nucleus (RTN), large subthreshold membrane potential oscillations contribute to the pacemaker-like action potential discharge. The oscillations and firing in LC and SCN involve contributions from leak sodium (NALCN) and L-type calcium channels while recent work from RTN suggested an additional pivotal role for a secondary calcium-activated and voltage-gated cationic current carried by TRPM4. Here, we tested whether TRPM4 contributes to subthreshold oscillations in mouse LC and SCN. By RNAscope in situ hybridization, Trpm4 transcripts were detected in both cell groups. In whole cell recordings from acute slice preparations, prominent voltage-dependent membrane potential oscillations were revealed in...

Neurons in the developing visual cortex undergo progressive functional maturation as indicated by the refinement of their visual feature selectivity. However, changes of the synaptic architecture underlying the maturation of spatial visual receptive fields (RFs) per se remain largely unclear. Here, loose-patch as well as single-unit recordings in layer 4 of mouse primary visual cortex (V1) of both sexes revealed that RF development in a post-eye-opening period is marked by an increased proportion of cortical neurons with spatially defined RFs, together with the increased signal-to-noise ratio (SNR) of spiking responses. By exploring excitatory and inhibitory synaptic RFs with whole-cell voltage clamp recordings, we observed a balanced enhancement of both synaptic excitation and inhibition, and that while the excitatory subfield size remains relatively constant during development, the inhibitory subfield is broadened. This balanced developmental strengthening of excitatory and inhibitory synaptic inputs res...

Bilateral cochlear implants (BI-CIs) or a CI for single-sided deafness (SSD; one normally functioning acoustic ear) can partially restore spatial-hearing abilities, including sound localization and speech understanding in noise. For these populations, however, interaural place-of-stimulation mismatch can occur and thus diminish binaural sensitivity that relies on interaurally frequency-matched neurons. This study examined whether plasticity—reorganization of central neural pathways over time—can compensate for peripheral interaural place mismatch. We hypothesized differential plasticity across two systems: none for binaural processing but adaptation toward frequencies delivered by the specific electrodes for pitch perception. Interaural place mismatch was evaluated in 19 BI-CI and 23 SSD-CI human subjects (both sexes) using binaural processing (interaural-time-difference discrimination with simultaneous bilateral stimulation), pitch perception (pitch ranking for single electrodes or acoustic tones with seq...

Oligodendrocytes are vulnerable to genetic and environmental insults and its injury leads to demyelinating diseases. The roles of ErbB receptors in maintaining the CNS myelin integrity are largely unknown. Here we overactivate ErbB receptors that mediate signaling of either neuregulin or EGF family growth factors and found their synergistic activation caused deleterious outcomes in white matter. Sustained ErbB activation induced by the tetracycline-dependent mouse tool Plp -tTA resulted in demyelination, axonal degeneration, oligodendrocyte precursor cell (OPC) proliferation, astrogliosis, and microgliosis in white matter. Moreover, there was hypermyelination prior to these inflammatory pathological events. In contrast, sustained ErbB activation induced by another tetracycline-dependent mouse tool Sox10 +/rtTA caused hypomyelination in the corpus callosum and optic nerve, which appeared to be a developmental deficit and did not associate with OPC regeneration, astrogliosis, or microgliosis. By tracing the ...

In oscillatory circuits, some actions of neuromodulators depend on the oscillation frequency. However, the mechanisms are poorly understood. We explored this problem by characterizing neuromodulation of the lateral pyloric (LP) neuron of the crab stomatogastric ganglion (STG). Many peptide modulators, including proctolin, activate the same ionic current ( I MI) in STG neurons. Because I MI is fast and non-inactivating, its peak level does not depend on the temporal properties of neuronal activity. We found, however, that the amplitude and peak time of the proctolin-activated current in LP is frequency dependent. Because frequency affects the rate of voltage change, we measured these currents with voltage ramps of different slopes and found that proctolin activated two kinetically distinct ionic currents: the known I MI, whose amplitude is independent of ramp slope or direction, and an inactivating current ( I MI-T), which was only activated by positive ramps and whose amplitude increased with increasing ra...

We propose a model of the main rhythms in the hippocampal CA1 field: theta rhythm; slow, middle, and fast gamma rhythms; and ripple oscillations. We have based this on data obtained from animals behaving freely. We have considered the modes of neuronal discharges and the occurrence of local field potential oscillations in the theta and non-theta states at different inputs from the CA3 field, the medial entorhinal cortex, and the medial septum. In our work, we tried to reproduce the main experimental phenomena about rhythms in the CA1 field: the coupling of neurons to the phase of rhythms, cross-rhythm phase–phase coupling, and phase–amplitude coupling. Using computational experiments, we have proved the hypothesis that the descending phase of the theta rhythm in the CA1 field is formed by the input from the CA3 field via the Shaffer collaterals, and the ascending phase of the theta rhythm is formed by the IPSPs from CCK basket cells. The slow gamma rhythm is coupled to the descending phase of the theta rhy...

Heterogeneous nuclear ribonucleoprotein A1 (hnRNP A1) is an RNA binding protein (RBP) that is localized within neurons and plays crucial roles in RNA metabolism. Its importance in neuronal functioning is underscored from the study of its pathogenic features in many neurodegenerative diseases where neuronal hnRNP A1 is mislocalized from the nucleus to the cytoplasm resulting in loss of hnRNP A1 function. Here, we model hnRNP A1 loss-of-function by siRNA-mediated knock-down in differentiated Neuro-2a cells. Through RNA sequencing (RNA-seq) followed by gene ontology (GO) analyses, we show that hnRNP A1 is involved in important biological processes, including RNA metabolism, neuronal function, neuronal morphology, neuronal viability, and stress granule (SG) formation. We further confirmed several of these roles by showing that hnRNP A1 knock-down results in a reduction of neurite outgrowth, increase in cell cytotoxicity and changes in SG formation. In summary, these findings indicate that hnRNP A1 loss-of-func...

Postsynaptic responses depend on input patterns as well as short-term synaptic plasticity, summation, and postsynaptic membrane properties, but the interactions of those dynamics with realistic input patterns are not well understood. We recorded the responses of the two pyloric dilator (PD) muscles, cpv2a and cpv2b , that are innervated by and receive identical periodic bursting input from the same two motor neurons in the lobster Homarus americanus . Cpv2a and cpv2b showed quantitative differences in membrane nonlinearities and synaptic summation. At a short timescale, responses in both muscles were dominated by facilitation, albeit with different frequency and time dependence. Realistic burst stimulations revealed more substantial differences. Across bursts, cpv2a showed transient depression, whereas cpv2b showed transient facilitation. Steady-state responses to bursting input also differed substantially. Neither muscle had a monotonic dependence on frequency, but cpv2b showed particularly pronounced ban...

Simulation software for spiking neuronal network models matured in the past decades regarding performance and flexibility. But the entry barrier remains high for students and early career scientists in computational neuroscience since these simulators typically require programming skills and a complex installation. Here, we describe an installation-free Graphical User Interface (GUI) running in the web browser, which is distinct from the simulation engine running anywhere, on the student’s laptop or on a supercomputer. This architecture provides robustness against technological changes in the software stack and simplifies deployment for self-education and for teachers. Our new open-source tool, NEST Desktop, comprises graphical elements for creating and configuring network models, running simulations, and visualizing and analyzing the results. NEST Desktop allows students to explore important concepts in computational neuroscience without the need to learn a simulator control language before. Our experienc...

Human heading perception from optic flow is accurate for directions close to the straight-ahead and systematic biases emerge in the periphery ([Cuturi and Macneilage, 2013][1]; [Sun et al., 2020][2]). In pursuit of the underlying neural mechanisms, primate brain dorsal medial superior temporal (MSTd) area has been a focus because of its causal link with heading perception ([Gu et al., 2012][3]). Computational models generally explain heading sensitivity in individual MSTd neurons as a feedforward integration of motion signals from medial temporal (MT) area that resemble full-field optic flow patterns consistent with the preferred heading direction ([Britten, 2008][4]; [Mineault et al., 2012][5]). In the present simulation study, we quantified within the structure of this feedforward model how physiological properties of MT and MSTd shape heading signals. We found that known physiological tuning characteristics generally supported the accuracy of heading estimation, but not always. A weak-to-moderate overre...