Function of lateral Inhibition in layer 2/3 of adult mouse barrel cortex
Final Report Abstract
How is a sensory stimulus presented and processed in the corresponding sensory cortical area and what is the role of a specific subtype of inhibitory neuron, the so-called parvalbumin (PV) expressing interneuron, in this intracortical information processing? To address these questions, we studied in a well-established animal model, the whisker-to-barrel cortex system of the adult mouse, with in vitro (single-cell patch-clamp recordings) and in vivo electrophysiological methods (multi-electrode intracortical recordings), optogenetic manipulation of PV interneurons and theoretical analyses using machine learning algorithms three central questions: (1) What is the influence of a transient optogenetic inhibition or activation of PV interneurons on spontaneous and stimulus-evoked neuronal activity in barrel cortex of adult mice? (2) What is the relationship between specific neuronal activity patterns and the spatio-temporal discrimination performance in awake mice ("neural code")? (3) What is the influence of a transient optogenetic inhibition of PV interneurons on psychophysical discrimination performance? (1) We found that inhibiting a small number of PV interneurons impacts cortical excitability most strongly during the first 20 ms after onset of sensory (whisker) stimulation. This effect is mediated by a rather small number of PV interneurons, constituting only around 10% of the local PV population. Our data further demonstrate that PV interneurons play a highly specific role in cross-columnar (as opposed to intracolumnar) cortical inhibition. (2) Head-fixed mice performed a single-whisker go/no-go detection task and cortical activity was recorded simultaneously in all layers of the whisker-related column with multi-electrode arrays. We simultaneously videotaped movements of the whiskers, the snout and the tongue. We found that maximum neurometric performance is achieved after about 30–50 ms following stimulus onset and that neurometric sensitivity is highest in cortical layer 4. Narrow-spike single units (presumably inhibitory interneurons) respond faster and stronger to sensory stimulation than broad-spike units (presumably excitatory neurons). Better psychometric performance is observed when animals abstain from whisking, which was associated with higher stimulusevoked firing rates for near-threshold stimulus intensities. In a computational approach, we studied the nature of first spike time noise correlations for excitatory (E) and inhibitory (I) connections in pairs of neurons. We found that spike time correlations were found for E–E, I–I and E–I neuron pairs separated over multiple layers and (up to 4) cortical columns. The most correlations were found between E-type neurons in L5A and L5B/6 of the principal and neighbouring columns. (3) Here we applied different spatiotemporal stimulation patterns to one or two whiskers, combined with multi-electrode recordings. We found that PV inhibition increased network power, especially in the beta band and also increased stimulus-evoked response amplitudes. Furthermore, stimulus-specific components of response profiles were attenuated when PV interneurons were inhibited, implying these neurons in temporal stimulus processing. Thus, local inhibition by PV interneurons is important for the faithful representation of stimulus patterns differing in the temporal domain. Surprisingly, mice trained on a psychophysical twowhisker discrimination task showed no evidence of impaired spatial discrimination performance during optogenetic PV inhibition.
Publications
- (2017) Optogenetic modulation of a minor fraction of parvalbumin-positive interneurons specifically affects spatiotemporal dynamics of spontaneous and sensory-evoked activity in mouse somatosensory cortex in vivo. Cereb Cortex 27: 5784-5803
Yang JW, Prouvot PH, Reyes-Puerta V, Stüttgen MC, Stroh A, Luhmann HJ
(See online at https://doi.org/10.1093/cercor/bhx261) - (2018) Combining Optogenetics with MEA, Depth-Resolved LFPs and Assessing the Scope of Optogenetic Network Modulation. In: Optogenetics: A Roadmap, edited by Stroh A. Springer, p. 133-152
Yang JW, Prouvot PH, Stroh A, Luhmann HJ
(See online at https://doi.org/10.1007/978-1-4939-7417-7_8) - (2021) Clustering and control for adaptation uncovers time‑warped spike time patterns in cortical networks in vivo. Scientific Reports 11: 15066
Isbister JB, Reyes-Puerta V, Sun JJ, Horenko I, Luhmann HJ
(See online at https://doi.org/10.1038/s41598-021-94002-0)
