Identification of a brainstem circuit regulating visual cortical state in parallel with locomotion
Open accessAbstract
Sensory processing is dependent upon behavioral state. In mice, locomotion is accompanied by changes in cortical state and enhanced visual responses. Although recent studies have begun to elucidate intrinsic cortical mechanisms underlying this effect, the neural circuits that initially couple locomotion to cortical processing are unknown. The mesencephalic locomotor region (MLR) has been shown to be capable of initiating running and is associated with the ascending reticular activating system. Here, we find that optogenetic stimulation of the MLR in awake, head-fixed mice can induce both locomotion and increases in the gain of cortical responses. MLR stimulation below the threshold for overt movement similarly changed cortical processing, revealing that MLR's effects on cortex are dissociable from locomotion. Likewise, stimulation of MLR projections to the basal forebrain also enhanced cortical responses, suggesting a pathway linking the MLR to cortex. These studies demonstrate that the MLR regulates cortical state in parallel with locomotion.
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Locomotion is a homogeneous behavioral state tightly coupled to arousal.
“This is because locomotion—where place cell activity has been classically characterized—is a homogeneous behavioral state, tightly coupled to arousal32–35.”
From Place and behavioral modulation of hippocampal neurons during immobility (2026) · cites this paper as [35]
The Discussion (no page number available) says locomotion and changes in behavioral state are naturally recruited in tandem, supporting an association with alertness. It does not characterize locomotion as homogeneous, and the paper reports that cortical-state changes can occur without overt movement, so it does not establish an invariable coupling. (LLM, conf=0.86)
Experimental — accuracy not yet measuredDuring running, the behavioral state is more homogeneous and likely corresponds to a high-arousal state compared to immobility, where the internal state is more variable and spontaneously fluctuating.
“These data indicate that during running, the behavioral state is more homogeneous (and likely corresponding to a high-arousal state34–36) compared to immobility, where the internal state is more variable and spontaneously fluctuating.”
From Place and behavioral modulation of hippocampal neurons during immobility (2026) · cites this paper as [35]
Behavioral state is an important determinant of both the temporal precision of sensory responses and gamma-band synchronization.
“Behavioral state is an important determinant of both the temporal precision of sensory responses and gamma-band synchronization.”
From Waking state: rapid variations modulate neural and behavioral responses (2015) · cites this paper as Lee et al., 2014
Spontaneous or causally induced increases in arousal are associated with a monotonic increase in gamma-band synchronization in LFP and relative membrane potential power, and in spike-LFP phase locking.
“Spontaneous or causally induced increases in arousal are associated with a monotonic increase in gamma-band synchronization both in terms of local field potential and relative membrane potential power (Lee et al., 2014; Lima et al., 2011; McGinley et al., 2015; Reimer et al., 2014; Vinck et al., 2015), and spike-local field potential phase locking”
From Waking state: rapid variations modulate neural and behavioral responses (2015) · cites this paper as Lee et al., 2014
The high correlation between movement and basal forebrain cholinergic activity, and neurons in the region of the brainstem cholinergic nuclei, suggests that there may also be a high correlation between pupil diameter and the activity of these neurons.
“The high correlation between movement and basal forebrain cholinergic activity (Eggermann et al., 2014), and neurons in the region of the brainstem cholinergic nuclei (Lee et al., 2014) suggests that there may also be a high correlation between pupil diameter and the activity of these neurons.”
From Waking state: rapid variations modulate neural and behavioral responses (2015) · cites this paper as Lee et al., 2014
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- Authors
- Lee, A. M., Hoy, J. L., Bonci, A., Wilbrecht, L., Stryker, M. P., & Niell, C. M.
- Affiliations
- University of California, San Francisco (US)
- University of Oregon (US)
- National Institute on Drug Abuse (US)
- Ernest Gallo Clinic and Research Center (US)
- Corresponding author
- Niell, Cristopher M.
- Venue
- Neuron
- Publisher
- Elsevier BV
- Published
- 2014-07
- Volume
- 83
- Issue
- 2
- Pages
- 455-466
- ISSN
- 0896-6273 (ISSN-L)
- PMC
- PMC4151326
- OpenAlex
- W2150951291
- Cited by
- 282
- References
- 65
- Citations by year
- 2026: 9 · 2025: 15 · 2024: 32 · 2023: 26 · 2022: 23 · 2021: 23 · 2020: 32 · 2019: 24 · 2018: 26 · 2017: 30 · 2016: 22 · 2015: 17 · 2014: 3
- FWCI
- 13.38
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Neuron (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- eScholarship (California Digital Library) (submittedVersion)
- Funders
- National Institutes of Health (5rc2ns069350-02)
- National Institute of Mental Health (R01MH087542)
- National Eye Institute (R01EY023337, 1R01EY02874, P30EY002162, R01EY002874, DP2EY023190, F32EY024179)
- National Institute of General Medical Sciences (T32GM007618)
- National Institute of Neurological Disorders and Stroke (RC2-NS-069350, 1RC2NS069350)
- Topics
- Life Sciences › Neuroscience › Cognitive Neuroscience › Neural dynamics and brain function
- Life Sciences › Neuroscience › Cognitive Neuroscience › Visual perception and processing mechanisms
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Keywords
- mesencephalic locomotor region, brainstem, locomotion, cortical state, visual cortex, optogenetic stimulation, ascending reticular activating system, basal forebrain, sensory processing, head-fixed mice
- MeSH terms
- Animals, Brain Stem, Locomotion, Mesencephalon, Neural Pathways, Neurons, Photic Stimulation, Visual Cortex, Mice
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