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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                            Distinct Spiking Patterns of Excitatory and Inhibitory Neurons and LFP Oscillations in Prefrontal Cortex During Sensory Discrimination
                        
                    
    
            Prefrontal cortex (PFC) are broadly linked to various aspects of behavior. During sensory discrimination, PFC neurons can encode a range of task related information, including the identity of sensory stimuli and related behavioral outcome. However, it remains largely unclear how different neuron subtypes and local field potential (LFP) oscillation features in the mouse PFC are modulated during sensory discrimination. To understand how excitatory and inhibitory PFC neurons are selectively engaged during sensory discrimination and how their activity relates to LFP oscillations, we used tetrode recordings to probe well-isolated individual neurons, and LFP oscillations, in mice performing a three-choice auditory discrimination task. We found that a majority of PFC neurons, 78% of the 711 recorded individual neurons, exhibited sensory discrimination related responses that are context and task dependent. Using spike waveforms, we classified these responsive neurons into putative excitatory neurons with broad waveforms or putative inhibitory neurons with narrow waveforms, and found that both neuron subtypes were transiently modulated, with individual neurons’ responses peaking throughout the entire duration of the trial. While the number of responsive excitatory neurons remain largely constant throughout the trial, an increasing fraction of inhibitory neurons were gradually recruited as the trial progressed. Further examination of the coherence between individual neurons and LFPs revealed that inhibitory neurons exhibit higher spike-field coherence with LFP oscillations than excitatory neurons during all aspects of the trial and across multiple frequency bands. Together, our results demonstrate that PFC excitatory neurons are continuously engaged during sensory discrimination, whereas PFC inhibitory neurons are increasingly recruited as the trial progresses and preferentially coordinated with LFP oscillations. These results demonstrate increasing involvement of inhibitory neurons in shaping the overall PFC dynamics toward the completion of the sensory discrimination task. 
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                            - Award ID(s):
- 1848029
- PAR ID:
- 10294012
- Date Published:
- Journal Name:
- Frontiers in Physiology
- Volume:
- 12
- ISSN:
- 1664-042X
- Format(s):
- Medium: X
- Sponsoring Org:
- National Science Foundation
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