Inhibitory neurons shape electrical stimulation evoked network activity
🧠 Two weeks to SfN. The talk pulls one thread through a year of findings, and the thread is the inhibitory neuron.
⏱️ Timing first. Two patterns, same average rate, same total charge, only the spacing of the pulses different. In mouse cortex, 60% of 309 neurons answered one and not the other. Rearranging pulses in time changes which cells fire, and the cells it swings hardest are inhibitory. Eles et al. 2021, J Neural Eng: https://doi.org/10.1088/1741-2552/abc29c
🩸 Blood next. We stimulated and watched the vessels. Both the firing and the blood flow rose, then both fell, the activity dipping below baseline about five seconds after the current stopped. Parvalbumin interneurons are part of why. They open the vessels after a brief input, but not a sustained one. The same cell that quiets the circuit also stops calling for blood. Suematsu et al. 2024, J Neural Eng: https://doi.org/10.1088/1741-2552/ad3853 Rakymzhan et al. 2025, iScience: https://doi.org/10.1016/j.isci.2025.113965
🌊 Then the long view. Run 25 Hz for twelve weeks and epileptiform events appear in nearly half the mice, late, after the stimulation had looked safe for weeks. The drift toward seizures tracks the slow failure of inhibitory control. Suematsu, Vazquez, Kozai 2026, Biomaterials: https://doi.org/10.1016/j.biomaterials.2026.124276
⚡ So Chris Hughes imaged the inhibitory cells directly, parvalbumin and somatostatin, under eleven patterns in awake cortex. SOM stays silent until about 40 Hz, then switches on. PV fires fast and early. One pattern held the balance the others lost. Amplitude modulation, rising and falling like natural touch, kept excitation and inhibition matched and cut the adaptation that makes a sensation fade. Modulating frequency did not. Hughes & Kozai, presenting at SfN 2026 (NANO21.01). Groundwork: Hughes et al. 2025, iScience: https://doi.org/10.1016/j.isci.2025.112707
🩺 Every failure this year ran through these cells. The fading, the blood pulling back, the late seizures. The right pattern steers them instead of breaking them.
📅 NANO21.01, Monday November 16, 1 PM, Room 144. ICMS, inhibitory circuits, DBS, sensory restoration, come find me.
#SfN2026 #Neuroscience #Microstimulation #BrainStimulation #WhyBCIsFail
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