Hypocretin and Nicotine Excite the Same Thalamocortical Synapses in Prefrontal Cortex: Correlation with Improved Attention in Rat

Lambe, Evelyn K.; Olausson, Peter; Horst, Nicole K.; Taylor, Jane R.; Aghajanian, George K.

doi:10.1523/jneurosci.0719-05.2005

Cited by 122 publications

(107 citation statements)

References 29 publications

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“…However, we observe that nicotinic currents in layer VI neurons are relatively resistant to desensitization. This observation more closely parallels the nicotinic currents in the thalamus and thalamocortical axons and terminals (Gioanni et al, 1999;Lambe et al, 2005;Kawai et al, 2007). The variability in the desensitization of ␣ 4 ␤ 2 * nicotinic receptors may arise from differences in their subunit composition (McGehee and Role, 1995).…”

Section: Developmental Changes In Layer VI Nicotinic Receptorssupporting

confidence: 66%

“…Cortical nicotinic acetylcholine receptors are important for attention and effortful concentration (Rezvani and Levin, 2001;Granon et al, 2003;Lambe et al, 2005), and have been suggested to have long-lasting effects on the development of attention circuitry (Langley et al, 2005;Rodriguez and Bohlin, 2005;Schmitz et al, 2006). Abnormalities in cortical nicotinic binding have been demonstrated in several neurodevelopmental conditions, including autism (Perry et al, 2001;Martin-Ruiz et al, 2004), epilepsy (Picard et al, 2006), and schizophrenia (Breese et al, 2000;Marutle et al, 2001).…”

Section: Introductionmentioning

confidence: 99%

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Developmental Excitation of Corticothalamic Neurons by Nicotinic Acetylcholine Receptors

Kassam¹,

Herman²,

Goodfellow³

et al. 2008

J. Neurosci.

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129

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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 ␣ 4 ␤ 2 * 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 ϳ50% of the subsequent current elicited by acetylcholine. An allosteric modulator of ␣ 4 ␤ 2 ␣ 5 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.

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Section: Developmental Changes In Layer VI Nicotinic Receptorssupporting

confidence: 66%

Section: Introductionmentioning

confidence: 99%

Developmental Excitation of Corticothalamic Neurons by Nicotinic Acetylcholine Receptors

Kassam¹,

Herman²,

Goodfellow³

et al. 2008

J. Neurosci.

Self Cite

129

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“…reversed the effects of sleep deprivation on CMRglc levels in the thalamus (Fig. 6), a brain region highly susceptible to sleep deficits in humans (Thomas et al, 2000;Drummond and Brown, 2001;Lambe et al, 2005). The fact that nasal orexin-A was effective in reversing performance on High-load trials, even to a greater extent than in normal alert sessions, suggests that: 1) high cognitive load trials engage either different brain processes or the same processes to a greater extent than low cognitive load trials, and 2) "high load cognitive processes" may recruit many neurons that have orexin receptors that can be activated more effectively by peptide delivery via the nasal route (Fig.…”

Section: Discussionmentioning

confidence: 90%

Systemic and Nasal Delivery of Orexin-A (Hypocretin-1) Reduces the Effects of Sleep Deprivation on Cognitive Performance in Nonhuman Primates

Deadwyler¹,

Porrino²,

Siegel³

et al. 2007

J. Neurosci.

239

192

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Hypocretin-1 (orexin-A) was administered to sleep-deprived (30 -36 h) rhesus monkeys immediately preceding testing on a multi-image delayed match-to-sample (DMS) short-term memory task. The DMS task used multiple delays and stimulus images and effectively measures cognitive defects produced by sleep deprivation (Porrino et al., 2005). Two methods of administration of orexin-A were tested, intravenous injections (2.5-10.0 g/kg, i.v.) and a novel method developed for nasal delivery via an atomizer spray mist to the nostrils (dose estimated 1.0 g/kg). Results showed that orexin-A delivered via the intravenous and nasal routes significantly improved performance in sleep-deprived monkeys; however, the nasal delivery method was significantly more effective than the highest dose (10 g/kg) of intravenous orexin-A tested. The improvement in performance by orexin-A was specific to trials classified as high versus low cognitive load as determined by performance difficulty under normal testing conditions. Except for the maximum intravenous dose (10 g/kg), neither delivery method affected task performance in alert non-sleep-deprived animals. The improved performance in sleep-deprived animals was accompanied by orexin-A related alterations in local cerebral glucose metabolism (CMRglc) in specific brain regions shown previously to be engaged by the task and impaired by sleep deprivation (Porrino et al., 2005). Consistent with the differential effects on performance, nasal delivered orexin-A produced a more pronounced reversal of sleep deprivation induced changes in brain metabolic activity (CMRglc) than intravenous orexin-A. These findings provide strong evidence for the effectiveness of intranasal orexin-A in alleviating cognitive deficits produced by loss of sleep.

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“…Nicotine increases some measures of EEG alertness (Griesar et al, 2002) but its mechanism is not solely cholinergic because nicotine acts presynaptically on neurons utilizing different neurotransmitters. Nicotine has produced similar effects to hypocretin on sustained attention in rats (Lambe et al, 2005).…”

Section: 22mentioning

confidence: 89%

Vigilance, alertness, or sustained attention: physiological basis and measurement

Oken

Salinsky

Elsas

2006

Clinical Neurophysiology

660

463

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Vigilance is a term with varied definitions but the most common usage is sustained attention or tonic alertness. This usage of vigilance implies both the degree of arousal on the sleep-wake axis and the level of cognitive performance. There are many interacting neural and neurotransmitter systems that affect vigilance. Most studies of vigilance have relied on states where the sleep-wake state is altered, e.g. drowsiness, sleep-deprivation, and CNS-active drugs, but there are factors ranging from psychophysics to motivation that may impact vigilance. While EEG is the most commonly studied physiologic measure of vigilance, various measures of eye movement and of autonomic nervous system activity have also been used. This review paper discusses the underlying neural basis of vigilance and its assessment using physiologic tools. Since, assessment of vigilance requires assessment of cognitive function this aspect is also discussed.

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Hypocretin and Nicotine Excite the Same Thalamocortical Synapses in Prefrontal Cortex: Correlation with Improved Attention in Rat

Cited by 122 publications

References 29 publications

Developmental Excitation of Corticothalamic Neurons by Nicotinic Acetylcholine Receptors

Developmental Excitation of Corticothalamic Neurons by Nicotinic Acetylcholine Receptors

Systemic and Nasal Delivery of Orexin-A (Hypocretin-1) Reduces the Effects of Sleep Deprivation on Cognitive Performance in Nonhuman Primates

Vigilance, alertness, or sustained attention: physiological basis and measurement

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