Muscarinic and nicotinic responses in the developing pedunculopontine nucleus (PPN)

Good, Cameron H.; Bay, Kevin D.; Buchanan, Roger; Skinner, R.D.; García‐Rill, Edgar

doi:10.1016/j.brainres.2006.10.046

Cited by 19 publications

(12 citation statements)

References 31 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The PPT is in close anatomical proximity to the LDT and includes another large collection of mesopontine cholinergic neurons. PPT cells recorded from animals between ages P12-17, and identified as cholinergic based on presence of A-type current, responded to bath-applied DMPP with depolarization (Good et al , 2007) which agrees with our findings in the mouse. However, by age 21 days, in a striking response reversal, DMPP was reported to elicit membrane hyperpolarization (Good et al , 2007).…”

Section: Discussionsupporting

confidence: 90%

“…PPT cells recorded from animals between ages P12-17, and identified as cholinergic based on presence of A-type current, responded to bath-applied DMPP with depolarization (Good et al , 2007) which agrees with our findings in the mouse. However, by age 21 days, in a striking response reversal, DMPP was reported to elicit membrane hyperpolarization (Good et al , 2007). In our study, we never observed a hyperpolarization in nNOS+ or nNOS- neurons in response to nicotine even though we recorded from animals up to 45 days of age and used two methods of agonist application.…”

Section: Discussionsupporting

confidence: 90%

See 1 more Smart Citation

Nicotinic Activation of Laterodorsal Tegmental Neurons: Implications for Addiction to Nicotine

Ishibashi

Leonard

Kohlmeier

2009

Neuropsychopharmacol

View full text Add to dashboard Cite

Identifying the neurological mechanisms underlying nicotine reinforcement is a healthcare imperative if society is to effectively combat tobacco addiction. The majority of studies of the neurobiology of addiction have focused on dopamine (DA)-containing neurons of the ventral tegmental area (VTA). However, recent data suggests that neurons of the laterodorsal tegmental (LDT) nucleus which sends cholinergic, GABAergic- and glutamatergic-containing projections to DA-containing neurons of the VTA are critical to gating normal functioning of this nucleus. The actions of nicotine on LDT neurons are unknown. We addressed this issue by examination of nicotinic effects on identified cholinergic and non-cholinergic LDT neurons using whole-cell patch clamp and Ca2+ imaging methods in brain slices from mice (P12-P45). Nicotine applied via puffer pipette or bath superfusion elicited membrane depolarization that often induced firing and TTX-resistant inward currents. Nicotine also enhanced sensitivity to injected current; and, baseline changes in intracellular calcium were elicited in the dendrites of some cholinergic LDT cells. Additionally, activity-dependent calcium transients were increased, suggesting that nicotine exposure sufficient to induce firing may lead to enhancement of levels of intracellular calcium. Nicotine also had strong actions on glutamate and GABA-releasing presynaptic terminals since it greatly increased the frequency of miniature EPSCs and IPSCs to both cholinergic and non-cholinergic neurons. Utilization of nAChR subunit antagonists revealed that presynaptic, inhibitory terminals on cholinergic neurons were activated by receptors containing α7, β2 and non-α7 subunits; whereas, presynaptic glutamatergic terminals were activated by nAChRs comprised of non-α7 subunits. We also found that direct nicotinic actions on cholinergic LDT neurons were mediated by receptors containing α7, β2 and non-α7 subunits. These findings lead us to suggest that nicotine exposure from smoking will enhance both the excitability and synaptic modulation of cholinergic and non-cholinergic LDT neurons and increase their signature neurotransmitter outflow to target regions including the VTA. This may reinforce the direct actions of this drug within reward circuitry and contribute to encoding stimulus saliency.

show abstract

Section: Discussionsupporting

confidence: 90%

Section: Discussionsupporting

confidence: 90%

Nicotinic Activation of Laterodorsal Tegmental Neurons: Implications for Addiction to Nicotine

Ishibashi

Leonard

Kohlmeier

2009

Neuropsychopharmacol

View full text Add to dashboard Cite

show abstract

“…ACh plays an important role in communication between nuclei of the RAS, particularly between the PPN and Pf. Both nuclei are known to receive the cholinergic afferents (26, 27). In our previous studies, we showed that both PPN and Pf cells have similar mechanisms involving high threshold, voltage-dependent calcium channel-mediated gamma oscillations that can increase in frequency under persistent application of CAR (30 μM) (3, 28).…”

Section: Resultsmentioning

confidence: 99%

Muscarinic Modulation of High Frequency Oscillations in Pedunculopontine Neurons

et al. 2013

Self Cite

View full text Add to dashboard Cite

We previously reported that persistent application of the non-specific cholinergic agonist carbachol (CAR) increased the frequency of calcium channel-mediated oscillatory activity in pedunculopontine nucleus (PPN) neurons, which we identified as dependent on voltage-gated, high-threshold P/Q-type channels. Here, we tested the hypothesis that M2 muscarinic receptors and G-proteins associated with M2 receptors mediate the increase in oscillatory frequency in PPN neurons. We found, using depolarizing ramps, that patch clamped 9–12 day old rat PPN neurons (n = 189) reached their peak oscillatory activity around −20 mV membrane potential. Acute (short duration) application of CAR blocked the oscillatory activity through M2 muscarinic receptors, an effect blocked by atropine. However, persistent (long duration) application of CAR significantly increased the frequency of oscillatory activity in PPN neurons through M2 receptors [40 ± 1 Hz (with CAR) vs. 23 ± 1 Hz (without CAR); p < 0.001]. We then tested the effects of the G-protein antagonist guanosine 5′-[β-thio] diphosphate trilithium salt (GDP-β-S), and the G-protein agonist 5′-[γ-thio] triphosphate trilithium salt (GTP-γ-S). We found, using a three-step protocol in voltage-clamp mode, that the increase in the frequency of oscillations induced by M2 cholinergic receptors was linked to a voltage-dependent G-protein mechanism. In summary, these results suggest that persistent cholinergic input creates a permissive activation state in the PPN that allows high frequency P/Q-type calcium channel-mediated gamma oscillations to occur.

show abstract

“…However, the change during development (early excitation, later inhibition) mirrors the effects of the GABAa agonist muscimol on PPN neurons . The possibility remains that DMPP may act through presynaptic excitation of GABAergic terminals that were not affected by TTX and the transmitter antagonists used (Good et al, 2006). Nevertheless, the important finding is that at least some PPN neurons were inhibited by this nicotinic agonist, at least initially.…”

Section: Implications Of Nicotinic Input To Ppn Cellsmentioning

confidence: 99%

“…We recently found that the nicotinic agonist 1,1-dimethyl-4-phenylpiperazinium iodide (DMPP) (Phelan and Gallagher, 1992) depolarized PPN neurons early in development and later hyperpolarized them (Good et al, 2006). This effect was present during exposure to TTX and various receptor agonists, suggesting that at least some of the effects of DMPP were postsynaptic.…”

Section: Implications Of Nicotinic Input To Ppn Cellsmentioning

confidence: 99%

Smoking during pregnancy: Postnatal effects on arousal and attentional brain systems

et al. 2007

View full text Add to dashboard Cite

Prenatal exposure to cigarette smoke is known to produce lasting arousal, attentional and cognitive deficits in humans. The pedunculopontine nucleus (PPN), as the cholinergic arm of the reticular activating system (RAS), is known to modulate arousal, waking and REM sleep. Rapid eye movement (REM) sleep decreases between 10 and 30 days postnatally in the rat, with the greatest decrease occurring at 12-21 days. Pregnant dams were exposed to 150 ml of cigarette smoke for 15 min, 3 times per day, from day E14 until parturition, and the pups allowed to mature. We analyzed a) intrinsic membrane properties of PPN neurons in slices from pups aged 12-21 days, and b) the sleep state-dependent P13 auditory evoked potential, which is generated by PPN outputs, in animals allowed to age to adolescence. We found significant changes in the intrinsic membrane properties of PPN cells in prenatally exposed animals compared to intact ones, rendering these cells more excitable. In addition, we found disturbances in the habituation to repetitive stimulation in adolescent, freely moving animals, suggestive of a deficit in the process of sensory gating. These findings could explain some of the differences seen in individuals whose parents smoked during pregnancy, especially in terms of their hypervigilance and increased propensity for attentional deficits and cognitive/behavioral disorders.

show abstract

Muscarinic and nicotinic responses in the developing pedunculopontine nucleus (PPN)

Cited by 19 publications

References 31 publications

Nicotinic Activation of Laterodorsal Tegmental Neurons: Implications for Addiction to Nicotine

Nicotinic Activation of Laterodorsal Tegmental Neurons: Implications for Addiction to Nicotine

Muscarinic Modulation of High Frequency Oscillations in Pedunculopontine Neurons

Smoking during pregnancy: Postnatal effects on arousal and attentional brain systems

Contact Info

Product

Resources

About