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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Activation and depression of neural and hemodynamic responses induced by the intracortical microstimulation and visual stimulation in the mouse visual cortex
- NSF-PAR ID:
- 10499632
- Publisher / Repository:
- IOP Publishing
- Date Published:
- Journal Name:
- Journal of Neural Engineering
- Volume:
- 21
- Issue:
- 2
- ISSN:
- 1741-2560
- Format(s):
- Medium: X Size: Article No. 026033
- Size(s):
- ["Article No. 026033"]
- Sponsoring Org:
- National Science Foundation
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image Key points The lateral perforant path (LPP)–dentate gyrus (DG) synapse operates as a low‐pass filter, where responses to a train of 50 Hz, γ frequency activation are greatly suppressed.
Activation with brief bursts of γ frequency information engages a secondary filter that persists for prolonged periods (lasting seconds).
Both forms of LPP frequency filtering are influenced by presynaptic, as opposed to postsynaptic, processes; this contrasts with other hippocampal synapses.
LPP frequency filtering is modified by the unique presynaptic long‐term potentiation at this synapse.
Computational simulations indicate that presynaptic factors associated with release probability and vesicle recycling may underlie the potent LPP–DG frequency filtering.
