QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

HOME  |   SEARCH  |   ARCHIVE  |   SUBSCRIBE  |   CONTACT  |   HELP

The Journal of Neuroscience, August 27, 2008, 28(35):8756-8764; doi:10.1523/JNEUROSCI.2645-08.2008

This Article Full Text Full Text (PDF) Supplemental Data Submit an eLetter Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Kassam, S. M. Articles by Lambe, E. K. Search for Related Content PubMed PubMed Citation Articles by Kassam, S. M. Articles by Lambe, E. K.

 Previous Article  |  Next Article 

Behavioral/Systems/Cognitive
Developmental Excitation of Corticothalamic Neurons by Nicotinic Acetylcholine Receptors

Sameera M. Kassam,^1 * Patrick M. Herman,^1 * Nathalie M. Goodfellow,¹ Nyresa C. Alves,¹ and Evelyn K. Lambe^1,2

Departments of ¹Physiology and ²Obstetrics and Gynaecology, University of Toronto, Toronto, Ontario, Canada M5S1A8

Correspondence should be addressed to Dr. Evelyn K. Lambe, Department of Physiology, University of Toronto, 1 King's College Circle, Toronto, Ontario, Canada MSS 1A8. Email: evelyn.lambe{at}utoronto.ca

In this study, we show robust nicotinic excitation of pyramidal neurons in layer VI of prefrontal cortex. This layer contains the corticothalamic neurons, which gate thalamic activity and play a critical role in attention. Our experiments tested nicotinic excitation across postnatal development, using whole-cell recordings in prefrontal brain slices from rats. These experiments showed that layer VI neurons have peak nicotinic currents during the first postnatal month, a time period of intensive cortical development in rodents. We demonstrate that these currents are mediated directly by postsynaptic nicotinic receptors and can be suppressed by a competitive antagonist of ₄β₂* nicotinic receptors. To record from identified corticothalamic neurons, we performed stereotaxic surgery to label the neurons projecting to medial dorsal thalamus. As hypothesized, recordings from these retrogradely labeled neurons in layer VI showed prominent nicotinic currents. Finally, we examined the effects of the drug nicotine on layer VI neurons and probed for the potential involvement of the accessory subunit, ₅, in their receptors. A level of nicotine similar to that found in the blood of smokers elicits a stable inward current in layer VI neurons, yet this exposure desensitizes 50% of the subsequent current elicited by acetylcholine. An allosteric modulator of ₄β₂₅ receptors resulted in a 2.5-fold potentiation of submaximal nicotinic currents. This result is consistent with the expression of the relatively rare ₅ nicotinic subunit in layer VI. In summary, we show that layer VI corticothalamic neurons can be strongly excited during development by an unusual subtype of nicotinic receptor.

Key words: corticothalamic neurons; postnatal development; nicotine; nicotinic receptors; prefrontal cortex; rat; slice

---

Received June 5, 2008; revised July 19, 2008; accepted July 24, 2008.

Correspondence should be addressed to Dr. Evelyn K. Lambe, Department of Physiology, University of Toronto, 1 King's College Circle, Toronto, Ontario, Canada MSS 1A8. Email: evelyn.lambe{at}utoronto.ca

Home  |   Search  |   Archive  |   Subscribe  |   Contact  |   Help