Sparse optical microstimulation in barrel cortex drives learned behaviour in freely moving mice
Open accessAbstract
Electrical microstimulation can establish causal links between the activity of groups of neurons and perceptual and cognitive functions. However, the number and identities of neurons microstimulated, as well as the number of action potentials evoked, are difficult to ascertain. To address these issues we introduced the light-gated algal channel channelrhodopsin-2 (ChR2) specifically into a small fraction of layer 2/3 neurons of the mouse primary somatosensory cortex. ChR2 photostimulation in vivo reliably generated stimulus-locked action potentials at frequencies up to 50 Hz. Here we show that naive mice readily learned to detect brief trains of action potentials (five light pulses, 1 ms, 20 Hz). After training, mice could detect a photostimulus firing a single action potential in approximately 300 neurons. Even fewer neurons (approximately 60) were required for longer stimuli (five action potentials, 250 ms). Our results show that perceptual decisions and learning can be driven by extremely brief epochs of cortical activity in a sparse subset of supragranular cortical pyramidal neurons.
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ChR2 has been used in other neural systems to activate specific cell populations and produce learning.
“The light activated channelrhodopsin (ChR2) (19, 20) has been used in other neural systems to activate specific cell populations and produce learning (21–23).”
From Optical activation of lateral amygdala pyramidal cells instructs associative fear learning (2010) · cites this paper as [23]
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“Alternative methods for manipulation include activation of excitatory neurons or stimulus selective sub ensembles, which were shown to trigger learned behaviors (Salzman et al. 1990; Huber et al. 2008; Sachidhanandam et al. 2013; Musall et al. 2014; Ceballo et al. 2019; Marshel et al. 2019; Buetfering et al. 2022).”
- Authors
- Huber, D., Petreanu, L., Ghitani, N., Ranade, S., Hromádka, T., Mainen, Z., & Svoboda, K.
- Affiliations
- Howard Hughes Medical Institute (US)
- Cold Spring Harbor Laboratory (US)
- Corresponding author
- Svoboda, Karel
- Venue
- Nature
- Published
- 2008-01
- Volume
- 451
- Issue
- 7174
- Pages
- 61-64
- ISSN
- 0028-0836 (ISSN-L)
- 1476-4687
- PMC
- PMC3425380
- OpenAlex
- W1963937305
- Cited by
- 539
- References
- 31
- Citations by year
- 2026: 5 · 2025: 6 · 2024: 10 · 2023: 17 · 2022: 22 · 2021: 21 · 2020: 21 · 2019: 41 · 2018: 30 · 2017: 32 · 2016: 22 · 2015: 36 · 2014: 32 · 2013: 37 · 2012: 32
- FWCI
- 16.39
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Cold Spring Harbor Laboratory Institutional Repository (Cold Spring Harbor Laboratory) (acceptedVersion)
- RePEc: Research Papers in Economics (submittedVersion)
- Funders
- Howard Hughes Medical Institute
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Photoreceptor and optogenetics research
- Life Sciences › Neuroscience › Cognitive Neuroscience › Neural dynamics and brain function
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Keywords
- channelrhodopsin-2, barrel cortex, primary somatosensory cortex, layer 2/3 neurons, action potential detection, perceptual learning, perceptual decision making, freely moving mice
- MeSH terms
- Action Potentials, Animals, Behavior, Animal, Cerebral Cortex, Electric Stimulation, Learning, Movement, Photic Stimulation, Pyramidal Cells, Algal Proteins, Rhodopsins, Microbial, Mice, Optics and Photonics
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