Perinatal exposure to nicotine causes deficits associated with a loss of nicotinic receptor function

Cohen, Gary; Roux, Jean‐Christophe; Grailhe, Régis; Malcolm, Girvan; Changeux, Jean‐Pierre; Lagercrantz, Hugo

doi:10.1073/pnas.0409782102

Cited by 122 publications

(102 citation statements)

References 44 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…8 E (mean change in the frequency, 12 Ϯ 6%; n ϭ 8), C, G (mean increase, 98 Ϯ 36%; n ϭ 6)]. These electrophysiological findings complement recent behavioral studies on the effects of prenatal nicotine exposure and nAChR mutant mice (Cohen et al, 2005) …”

Section: Exposure To Nicotine During Mid-prenatal and Early Perinatalsupporting

confidence: 74%

See 1 more Smart Citation

Cholinergic Modulation of Appetite-Related Synapses in Mouse Lateral Hypothalamic Slice

Jo¹,

Wiedl²,

Role³

2005

J. Neurosci.

View full text Add to dashboard Cite

Nicotine administration reduces appetite and alters feeding patterns; a major deterrent to smoking cessation is hyperphagia and resultant weight gain. We demonstrate here that lateral hypothalamic (LH) circuits involving melanin-concentrating hormone (MCH) neurons are subject to cholinergic modulation that may be related to the effects of nicotine on appetite control. Cholinergic input to the perifornical LH area of the mouse is confirmed by examination of immunostaining for vesicular acetylcholine (

show abstract

Section: Exposure To Nicotine During Mid-prenatal and Early Perinatalsupporting

confidence: 74%

“…The mechanism underlying this upregulation of inhibitory tone remains to be explained. One simple explanation is that the loss of presynaptic nAChRs in nicotine-exposed mice may alter GABA release at LH synapses (Cohen et al, 2005).…”

Section: Prenatal Exposure To Nicotinementioning

confidence: 99%

Cholinergic Modulation of Appetite-Related Synapses in Mouse Lateral Hypothalamic Slice

Jo¹,

Wiedl²,

Role³

2005

J. Neurosci.

View full text Add to dashboard Cite

show abstract

“…Nicotinic currents have also been reported in low-threshold spiking interneurons in layers II/III and V of visual cortex in young rats (Xiang et al, 1998), and of prefrontal cortex in young mice (Couey et al, 2007). It has been shown that knock-out mice deleted for all ␤2-containing nicotinic receptors have deficits in cortically mediated arousal processes (Granon et al, 2003;King et al, 2003;Cohen et al, 2005;Granon and Changeux, 2006). Interestingly, it has been found that the performance of these mice on a behav- ioral task of arousal can be normalized if ␤ 2 subunits are restored in corticothalamic neurons during the first 3 weeks of postnatal development (King et al, 2003).…”

Section: Developmental Changes In Layer VI Nicotinic Receptorsmentioning

confidence: 99%

Developmental Excitation of Corticothalamic Neurons by Nicotinic Acetylcholine Receptors

Kassam¹,

Herman²,

Goodfellow³

et al. 2008

J. Neurosci.

129

View full text Add to dashboard Cite

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.

show abstract

“…Remarkably similar deficits are detected in pups lacking β2-containing nAChRs. Loss-of-function of these nAChRs reproduces many of the abnormalities caused by perinatal nicotine exposure suggesting that nicotine's detrimental side effects on a range of crucial defensive reflexes involve loss of function of nAChR subtypes, possibly via activity-dependent desensitization [108] .…”

Section: Effects Of Perinatal Nicotine Exposure On Neonatal Respiratomentioning

confidence: 99%

Central cholinergic regulation of respiration: nicotinic receptors

Shao

Feldman

2009

Acta Pharmacol Sin

View full text Add to dashboard Cite

Nicotinic acetylcholine receptors (nAChRs) are expressed in brainstem and spinal cord regions involved in the control of breathing. These receptors mediate central cholinergic regulation of respiration and effects of the exogenous ligand nicotine on respiratory pattern. Activation of α4* nAChRs in the preBötzinger Complex (preBötC), an essential site for normal respiratory rhythm generation in mammals, modulates excitatory glutamatergic neurotransmission and depolarizes preBötC inspiratory neurons, leading to increases in respiratory frequency. nAChRs are also present in motor nuclei innervating respiratory muscles. Activation of post-and/or extra-synaptic α4* nAChRs on hypoglossal (XII) motoneurons depolarizes these neurons, potentiating tonic and respiratory-related rhythmic activity. As perinatal nicotine exposure may contribute to the pathogenesis of sudden infant death syndrome (SIDS), we discuss the effects of perinatal nicotine exposure on development of the cholinergic and other neurotransmitter systems involved in control of breathing. Advances in understanding of the mechanisms underlying central cholinergic/nicotinic modulation of respiration provide a pharmacological basis for exploiting nAChRs as therapeutic targets for neurological disorders related to neural control of breathing such as sleep apnea and SIDS.

show abstract

Perinatal exposure to nicotine causes deficits associated with a loss of nicotinic receptor function

Cited by 122 publications

References 44 publications

Cholinergic Modulation of Appetite-Related Synapses in Mouse Lateral Hypothalamic Slice

Cholinergic Modulation of Appetite-Related Synapses in Mouse Lateral Hypothalamic Slice

Developmental Excitation of Corticothalamic Neurons by Nicotinic Acetylcholine Receptors

Central cholinergic regulation of respiration: nicotinic receptors

Contact Info

Product

Resources

About