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1. Local glutamate-mediated dendritic plateau potentials change the state of the cortical pyramidal neuron

   https://doi.org/10.1152/jn.00734.2019  

   Gao, Peng P. ; Graham, Joseph W. ; Zhou, Wen-Liang ; Jang, Jinyoung ; Angulo, Sergio ; Dura-Bernal, Salvador ; Hines, Michael ; Lytton, William W. ; Antic, Srdjan D. ( January 2021 , Journal of Neurophysiology)

   null (Ed.)

   Dendritic spikes in thin dendritic branches (basal and oblique dendrites) are traditionally inferred from spikelets measured in the cell body. Here, we used laser-spot voltage-sensitive dye imaging in cortical pyramidal neurons (rat brain slices) to investigate the voltage waveforms of dendritic potentials occurring in response to spatially restricted glutamatergic inputs. Local dendritic potentials lasted 200–500 ms and propagated to the cell body, where they caused sustained 10- to 20-mV depolarizations. Plateau potentials propagating from dendrite to soma and action potentials propagating from soma to dendrite created complex voltage waveforms in the middle of the thin basal dendrite, comprised of local sodium spikelets, local plateau potentials, and backpropagating action potentials, superimposed on each other. Our model replicated these voltage waveforms across a gradient of glutamatergic stimulation intensities. The model then predicted that somatic input resistance ( R in ) and membrane time constant (tau) may be reduced during dendritic plateau potential. We then tested these model predictions in real neurons and found that the model correctly predicted the direction of R in and tau change but not the magnitude. In summary, dendritic plateau potentials occurring in basal and oblique branches put pyramidal neurons into an activated neuronal state (“prepared state”), characterized by depolarized membrane potential and smaller but faster membrane responses. The prepared state provides a time window of 200–500 ms, during which cortical neurons are particularly excitable and capable of following afferent inputs. At the network level, this predicts that sets of cells with simultaneous plateaus would provide cellular substrate for the formation of functional neuronal ensembles. NEW & NOTEWORTHY In cortical pyramidal neurons, we recorded glutamate-mediated dendritic plateau potentials with voltage imaging and created a computer model that recreated experimental measures from dendrite and cell body. Our model made new predictions, which were then tested in experiments. Plateau potentials profoundly change neuronal state: a plateau potential triggered in one basal dendrite depolarizes the soma and shortens membrane time constant, making the cell more susceptible to firing triggered by other afferent inputs. 

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2. Intracortical microstimulation pulse waveform and frequency recruits distinct spatiotemporal patterns of cortical neuron and neuropil activation

   https://doi.org/10.1088/1741-2552/ac5bf5  

   Stieger, Kevin C ; Eles, James R ; Ludwig, Kip A ; Kozai, Takashi D ( March 2022 , Journal of Neural Engineering)

   Abstract Objective . Neural prosthetics often use intracortical microstimulation (ICMS) for sensory restoration. To restore natural and functional feedback, we must first understand how stimulation parameters influence the recruitment of neural populations. ICMS waveform asymmetry modulates the spatial activation of neurons around an electrode at 10 Hz; however, it is unclear how asymmetry may differentially modulate population activity at frequencies typically employed in the clinic (e.g. 100 Hz). We hypothesized that stimulation waveform asymmetry would differentially modulate preferential activation of certain neural populations, and the differential population activity would be frequency-dependent. Approach . We quantified how asymmetric stimulation waveforms delivered at 10 or 100 Hz for 30 s modulated spatiotemporal activity of cortical layer II/III pyramidal neurons using in vivo two-photon and mesoscale calcium imaging in anesthetized mice. Asymmetry is defined in terms of the ratio of the duration of the leading phase to the duration of the return phase of charge-balanced cathodal- and anodal-first waveforms (i.e. longer leading phase relative to return has larger asymmetry). Main results . Neurons within 40–60 µ m of the electrode display stable stimulation-induced activity indicative of direct activation, which was independent of waveform asymmetry. The stability of 72% of activated neurons and the preferential activation of 20%–90% of neurons depended on waveform asymmetry. Additionally, this asymmetry-dependent activation of different neural populations was associated with differential progression of population activity. Specifically, neural activity tended to increase over time during 10 Hz stimulation for some waveforms, whereas activity remained at the same level throughout stimulation for other waveforms. During 100 Hz stimulation, neural activity decreased over time for all waveforms, but decreased more for the waveforms that resulted in increasing neural activity during 10 Hz stimulation. Significance. These data demonstrate that at frequencies commonly used for sensory restoration, stimulation waveform alters the pattern of activation of different but overlapping populations of excitatory neurons. The impact of these waveform specific responses on the activation of different subtypes of neurons as well as sensory perception merits further investigation. 

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3. Decoding network-mediated retinal response to electrical stimulation: implications for fidelity of prosthetic vision

   https://doi.org/10.1088/1741-2552/abc535  

   Ho, Elton ; Shmakov, Alex ; Palanker, Daniel ( December 2020 , Journal of Neural Engineering)

   Objective. Patients with photovoltaic subretinal implant PRIMA demonstrated letter acuity ∼0.1 logMAR worse than sampling limit for 100μm pixels (1.3 logMAR) and performed slower than healthy subjects tested with equivalently pixelated images. To explore the underlying differences between natural and prosthetic vision, we compare the fidelity of retinal response to visual and subretinal electrical stimulation through single-cell modeling and ensemble decoding.Approach. Responses of retinal ganglion cells (RGCs) to optical or electrical white noise stimulation in healthy and degenerate rat retinas were recorded via multi-electrode array. Each RGC was fit with linear–nonlinear and convolutional neural network models. To characterize RGC noise, we compared statistics of spike-triggered averages (STAs) in RGCs responding to electrical or visual stimulation of healthy and degenerate retinas. At the population level, we constructed a linear decoder to determine the accuracy of the ensemble of RGCs onN-way discrimination tasks.Main results. Although computational models can match natural visual responses well (correlation ∼0.6), they fit significantly worse to spike timings elicited by electrical stimulation of the healthy retina (correlation ∼0.15). In the degenerate retina, response to electrical stimulation is equally bad. The signal-to-noise ratio of electrical STAs in degenerate retinas matched that of the natural responses when 78 ± 6.5% of the spikes were replaced with random timing. However, the noise in RGC responses contributed minimally to errors in ensemble decoding. The determining factor in accuracy of decoding was the number of responding cells. To compensate for fewer responding cells under electrical stimulation than in natural vision, more presentations of the same stimulus are required to deliver sufficient information for image decoding.Significance. Slower-than-natural pattern identification by patients with the PRIMA implant may be explained by the lower number of electrically activated cells than in natural vision, which is compensated by a larger number of the stimulus presentations.

    

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4. Stimulus encoding by specific inactivation of cortical neurons

   https://doi.org/10.1038/s41467-024-47515-x  

   Pérez-Ortega, Jesús ; Akrouh, Alejandro ; Yuste, Rafael ( April 2024 , Nature Communications)

   Neuronal ensembles are groups of neurons with correlated activity associated with sensory, motor, and behavioral functions. To explore how ensembles encode information, we investigated responses of visual cortical neurons in awake mice using volumetric two-photon calcium imaging during visual stimulation. We identified neuronal ensembles employing an unsupervised model-free algorithm and, besides neurons activated by the visual stimulus (termed “onsemble”), we also find neurons that are specifically inactivated (termed “offsemble”). Offsemble neurons showed faster calcium decay during stimuli, suggesting selective inhibition. In response to visual stimuli, each ensemble (onsemble+offsemble) exhibited small trial-to-trial variability, high orientation selectivity, and superior predictive accuracy for visual stimulus orientation, surpassing the sum of individual neuron activity. Thus, the combined selective activation and inactivation of cortical neurons enhances visual encoding as an emergent and distributed neural code.

    

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5. Precision multidimensional neural population code recovered from single intracellular recordings

   https://doi.org/10.1038/s41598-020-72936-1  

   Johnson, James K. ; Geng, Songyuan ; Hoffman, Maximilian W. ; Adesnik, Hillel ; Wessel, Ralf ( September 2020 , Scientific Reports)

   Neurons in sensory cortices are more naturally and deeply integrated than any current neural population recording tools (e.g. electrode arrays, fluorescence imaging). Two concepts facilitate efforts to observe population neural code with single-cell recordings. First, even the highest quality single-cell recording studies find a fraction of the stimulus information in high-dimensional population recordings. Finding any of this missing information provides proof of principle. Second, neurons and neural populations are understood as coupled nonlinear differential equations. Therefore, fitted ordinary differential equations provide a basis for single-trial single-cell stimulus decoding. We obtained intracellular recordings of fluctuating transmembrane current and potential in mouse visual cortex during stimulation with drifting gratings. We use mean deflection from baseline when comparing to prior single-cell studies because action potentials are too sparse and the deflection response to drifting grating stimuli (e.g. tuning curves) are well studied. Equation-based decoders allowed more precise single-trial stimulus discrimination than tuning-curve-base decoders. Performance varied across recorded signal types in a manner consistent with population recording studies and both classification bases evinced distinct stimulus-evoked phases of population dynamics, providing further corroboration. Naturally and deeply integrated observations of population dynamics would be invaluable. We offer proof of principle and a versatile framework.

    

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