Hypocretin and Nicotine Excite the Same Thalamocortical Synapses in Prefrontal Cortex: Correlation with Improved Attention in Rat
Open accessAbstract
Thalamic projections to prefrontal cortex are important for executive aspects of attention. Using two-photon imaging in prefrontal brain slices, we show that nicotine and the wakefulness neuropeptide hypocretin (orexin) excite the same identified synapses of the thalamocortical arousal pathway within the prefrontal cortex. Although it is known that attention can be improved when nicotine is infused directly into the midlayer of the prefrontal cortex in the rat, the effects of hypocretin on attention are not known. The overlap in thalamocortical synapses excited by hypocretin and nicotine and the lack of direct postsynaptic effects prompted us to compare their effects on a sustained and divided attention task in the rat. Similar to nicotine, infusions of hypocretin-2 peptide into the prefrontal cortex significantly improved accuracy under high attentional demand without effects on other performance measures. We show for the first time that hypocretin can improve attentional processes relevant to executive functions of the prefrontal cortex.
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nAChRs on glutamatergic thalamocortical neurons impinging on layer 5 pyramidal neurons in the prefrontal cortex are an important site for nAChR control of attention.
“Studies in rodents have also implicated nAChRs on glutamatergic thalamocortical neurons impinging on layer 5 pyramidal neurons in the prefrontal cortex as an important site for nAChR control of attention (Lambe et al. 2005;Bailey et al. 2010).”
From Mechanisms of Nicotine Addiction (2021) · cites this paper as Lambe et al. 2005
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Prefrontal executive and cognitive functions in rodents: neural and neurochemical substrates
Dalley, J. W., Cardinal, R. N., & Robbins, T. W. (2004) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2004.09.006 · Cited by 1,329 · see citing works
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The Neuropsychopharmacology of Fronto-Executive Function: Monoaminergic Modulation
Robbins, T. W., & Arnsten, A. F. T. (2009) · Annual Review of Neuroscience · doi:10.1146/annurev.neuro.051508.135535 · Cited by 957 · see citing works
Vigilance, alertness, or sustained attention: physiological basis and measurement
Oken, B. S., Salinsky, M. C., & Elsas, S. M. (2006) · Clinical Neurophysiology · doi:10.1016/j.clinph.2006.01.017 · Cited by 887 · see citing works
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Self-citationGain Modulation by Nicotine in Macaque V1
Disney, A. A., Aoki, C., & Hawken, M. J. (2007) · Neuron · doi:10.1016/j.neuron.2007.09.034 · Cited by 331 · see citing works
Mechanisms of Nicotine Addiction
Picciotto, M. R., & Kenny, P. J. (2021) · Cold Spring Harbor Perspectives in Medicine · doi:10.1101/cshperspect.a039610 · Cited by 157 · see citing works
The Nicotinic Acetylcholine Receptor 5 Subunit Plays a Key Role in Attention Circuitry and Accuracy
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Self-citationOrexins Mediate Sex Differences in the Stress Response and in Cognitive Flexibility
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Developmental Excitation of Corticothalamic Neurons by Nicotinic Acetylcholine Receptors
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- Authors
- Lambe, E. K., Olausson, P., Horst, N. K., Taylor, J. R., & Aghajanian, G. K.
- Affiliations
- Yale University (US)
- Institut Interdisciplinaire de Neuroscience (FR)
- Venue
- The Journal of Neuroscience
- Publisher
- Society for Neuroscience
- Published
- 2005-05-25
- Volume
- 25
- Issue
- 21
- Pages
- 5225-5229
- ISSN
- 0270-6474 (ISSN-L)
- 1529-2401
- PMC
- PMC6724823
- OpenAlex
- W1980643144
- Cited by
- 135
- References
- 1
- Citations by year
- 2026: 1 · 2025: 5 · 2024: 6 · 2023: 2 · 2022: 2 · 2021: 5 · 2020: 8 · 2019: 3 · 2018: 6 · 2017: 8 · 2016: 6 · 2015: 6 · 2014: 9 · 2013: 12 · 2012: 9
- FWCI
- 2.98
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Neuroscience (publishedVersion, cc-by-nc-sa)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Yale University
- National Alliance for Research on Schizophrenia and Depression
- National Institutes of Health (MH17871)
- National Institute on Alcohol Abuse and Alcoholism (1 P50 AA15632, P50AA015632)
- National Institute of Mental Health (MH 17871, R37MH017871, R01MH017871)
- National Institute on Drug Abuse (DA 11717, R01DA011717)
- Topics
- Life Sciences › Neuroscience › Cognitive Neuroscience › Sleep and Wakefulness Research
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Nicotinic Acetylcholine Receptors Study
- Keywords
- orexin, nicotine, thalamocortical synapses, prefrontal cortex, attention, executive function, sustained attention, divided attention, arousal, two-photon imaging, hypocretin-2
- MeSH terms
- Orexins, Action Potentials, Afferent Pathways, Animals, Animals, Newborn, Attention, Behavior, Animal, Calcium, Diagnostic Imaging, Neurons, Neuropeptides, Nicotine, Synapses, Thalamus, Rats, Sprague-Dawley, Prefrontal Cortex, Photons, Nicotinic Agonists, Intracellular Signaling Peptides and Proteins, Rats, In Vitro Techniques
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