Nicotine Blocks the Hyperpolarization-Activated Current<i>I</i><sub>h</sub>and Severely Impairs the Oscillatory Behavior of Oriens-Lacunosum Moleculare Interneurons

Griguoli, Marilena; Maul, Alena; Nguyen, Chuong; Giorgetti, Alejandro; Carloni, Paolo; Cherubini, Enrico

doi:10.1523/jneurosci.2446-10.2010

Cited by 36 publications

(52 citation statements)

References 59 publications

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“…We show for the first time that nicotine decreases the Ih current present in cholinergic LDT neurons, which corroborates findings of a nicotine-mediated decrease of this current seen in cortical neurons (Griguoli et al, 2010). Additionally, our current study confirms developmental changes in Ih current seen in a subset of cholinergic LDT neurons in C57BL6 mice (Kristensen et al, 2007) and extends them to bnos-identified neurons of the LDT in NMRI mice.…”

Section: Discussionsupporting

confidence: 90%

“…Cholinergic LDT neurons possess a prominent Ih current, which in response to hyperpolarizations significantly more negative than resting membrane potential, can induce a strong depolarizing effect (Biel et al, 2009) and nicotine has been shown to decrease Ih current in cortical neurons (Griguoli et al, 2010). We therefore examined developmental- and nicotine-induced changes in the Ih current of both cholinergic and non-cholinergic LDT neurons.…”

Section: Resultsmentioning

confidence: 99%

“…Nicotine significantly decreased the spike amplitude (5.1 ± 1.8 % reduction, n= 16,), a phenomenon also seen in bnos positive cells (n= 8) (see table II). As nicotine activates nAChRs permeable to Na + and K + and has actions on other membrane conductances (Griguoli et al, 2010; Nutter and Adams, 1995), nicotine-mediated reductions in spike amplitude could be due to shunting of current across the membrane due to alterations in membrane conductance (Zhang et al, 2004). In addition, we also observed a 8.8 ± 3.8 % decrease of the maximum decay slopes of the action potential in the presence of nicotine, which was significant and a similar phenomenon was seen in bnos positive cells (8.7 ± 4.9 %, p< 0.05).…”

Section: Resultsmentioning

confidence: 99%

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Age-related changes in nicotine response of cholinergic and non-cholinergic laterodorsal tegmental neurons: Implications for the heightened adolescent susceptibility to nicotine addiction

et al. 2014

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The younger an individual starts smoking, the greater the likelihood that addiction to nicotine will develop, suggesting that neurobiological responses vary across age to the addictive component of cigarettes. Cholinergic neurons of the laterodorsal tegmental nucleus (LDT) are importantly involved in the development of addiction, however, the effects of nicotine on LDT neuronal excitability across ontogeny are unknown. Nicotinic effects on several parameters affecting LDT cells across different age groups were examined using calcium imaging and whole-cell patch clamping. Within the youngest age group (P7-P15), nicotine was found to induce larger intracellular calcium transients and inward currents. Nicotine induced a greater number of excitatory synaptic currents in the youngest animals, whereas larger amplitude inhibitory synaptic events were induced in cells from the oldest animals (P15-P34). Nicotine increased neuronal firing of cholinergic cells to a greater degree in younger animals, possibly linked to development associated differences found in nicotinic effects on action potential shape and afterhyperpolarization. We conclude that in addition to age-associated alterations of several properties expected to affect resting cell excitability, parameters affecting cell excitability are altered by nicotine differentially across ontogeny. Taken together, our data suggest that nicotine induces a larger excitatory response in cholinergic LDT neurons from the youngest animals, which could result in a greater excitatory output from these cells to target regions involved in development of addiction. Such output would be expected to be promotive of addiction; therefore, ontogenetic differences in nicotine-mediated increases in the excitability of the LDT could contribute to the differential susceptibility to nicotine addiction seen across age.

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Section: Discussionsupporting

confidence: 90%

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

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Age-related changes in nicotine response of cholinergic and non-cholinergic laterodorsal tegmental neurons: Implications for the heightened adolescent susceptibility to nicotine addiction

et al. 2014

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“…The effective concentration to block I h in vitro is between 25 and 100 mM (Hutcheon et al, 1996;Dickson et al, 2000) and we assumed that the final diluted concentration of infusate should be within this range for the upper end of our dilution factor. Both hippocampal pyramidal cells and interneurons express I h , which plays an essential role in terms of intrinsic membrane theta oscillations and resonance (Chapman and Lacaille, 1999b;Hu et al, 2002;Griguoli et al, 2010;Zemankovics et al, 2010). Insofar as synchronizing influences are concerned, the effects of ZD7288 upon specific interneuronal populations like those in stratum oriens or lacunosum moleculare may be the most relevant since these cells can prominently pace activity in both pyramidal cells and other non-theta oscillatory interneurons (Cobb et al, 1995;Chapman and Lacaille, 1999a;Pike et al, 2000).…”

Section: Discussionmentioning

confidence: 99%

Intrahippocampal infusion of the I_h blocker ZD7288 slows evoked theta rhythm and produces anxiolytic‐like effects in the elevated plus maze

2012

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Hippocampal theta rhythm has been associated with a number of behavioral processes, including learning and memory, spatial behavior, sensorimotor integration and affective responses. Suppression of hippocampal theta frequency has been shown to be a reliable neurophysiological signature of anxiolytic drug action in tests using known anxiolytic drugs (i.e., correlational evidence), but only one study to date (Yeung et al. (2012) Neuropharmacology 62:155-160) has shown that a drug with no known effect on either hippocampal theta or anxiety can in fact separately suppress hippocampal theta and anxiety in behavioral tests (i.e., prima facie evidence). Here, we attempt a further critical test of the hippocampal theta model by performing intrahippocampal administrations of the Ih blocker ZD7288, which is known to disrupt theta frequency subthreshold oscillations and resonance at the membrane level but is not known to have anxiolytic action. Intrahippocampal microinfusions of ZD7288 at high (15 µg), but not low (1 µg) doses slowed brainstem-evoked hippocampal theta responses in the urethane anesthetized rat, and more importantly, promoted anxiolytic action in freely behaving rats in the elevated plus maze. Taken together with our previous demonstration, these data provide converging, prima facie evidence of the validity of the theta suppression model.

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“…HCN currents enhance subthreshold oscillations in entorhinal cortex, potently facilitating the generation of rhythmic and synchronous hippocampal activity (Dickson et al 2000). I h inhibition disrupts theta frequency oscillations in hippocampal interneurons (Griguoli et al 2010) and CA1 pyramidal neurons (Marcelin et al 2009). Also, the strength and frequency of intrathalamic network oscillations are altered by changes in I h (Yue and Huguenard 2001).…”

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confidence: 99%

Regulation of epileptiform discharges in rat neocortex by HCN channels

Albertson

Williams

Hablitz

2013

Journal of Neurophysiology

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Albertson AJ, Williams SB, Hablitz JJ. Regulation of epileptiform discharges in rat neocortex by HCN channels. J Neurophysiol 110: 1733-1743, 2013. First published July 17, 2013 doi:10.1152/jn.00955.2012.-Hyperpolarization-activated, cyclic nucleotide-gated, nonspecific cation (HCN) channels have a well-characterized role in regulation of cellular excitability and network activity. The role of these channels in control of epileptiform discharges is less thoroughly understood. This is especially pertinent given the altered HCN channel expression in epilepsy. We hypothesized that inhibition of HCN channels would enhance bicuculline-induced epileptiform discharges. Whole cell recordings were obtained from layer (L)2/3 and L5 pyramidal neurons and L1 and L5 GABAergic interneurons. In the presence of bicuculline (10 M), HCN channel inhibition with ZD 7288 (20 M) significantly increased the magnitude (defined as area) of evoked epileptiform events in both L2/3 and L5 neurons. We recorded activity associated with epileptiform discharges in L1 and L5 interneurons to test the hypothesis that HCN channels regulate excitatory synaptic inputs differently in interneurons versus pyramidal neurons. HCN channel inhibition increased the magnitude of epileptiform events in both L1 and L5 interneurons. The increased magnitude of epileptiform events in both pyramidal cells and interneurons was due to an increase in network activity, since holding cells at depolarized potentials under voltage-clamp conditions to minimize HCN channel opening did not prevent enhancement in the presence of ZD 7288. In neurons recorded with ZD 7288-containing pipettes, bath application of the noninactivating inward cationic current (I h ) antagonist still produced increases in epileptiform responses. These results show that epileptiform discharges in disinhibited rat neocortex are modulated by HCN channels.

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Nicotine Blocks the Hyperpolarization-Activated CurrentI_hand Severely Impairs the Oscillatory Behavior of Oriens-Lacunosum Moleculare Interneurons

Cited by 36 publications

References 59 publications

Age-related changes in nicotine response of cholinergic and non-cholinergic laterodorsal tegmental neurons: Implications for the heightened adolescent susceptibility to nicotine addiction

Age-related changes in nicotine response of cholinergic and non-cholinergic laterodorsal tegmental neurons: Implications for the heightened adolescent susceptibility to nicotine addiction

Intrahippocampal infusion of the I_h blocker ZD7288 slows evoked theta rhythm and produces anxiolytic‐like effects in the elevated plus maze

Regulation of epileptiform discharges in rat neocortex by HCN channels

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Nicotine Blocks the Hyperpolarization-Activated CurrentIhand Severely Impairs the Oscillatory Behavior of Oriens-Lacunosum Moleculare Interneurons

Cited by 36 publications

References 59 publications

Age-related changes in nicotine response of cholinergic and non-cholinergic laterodorsal tegmental neurons: Implications for the heightened adolescent susceptibility to nicotine addiction

Age-related changes in nicotine response of cholinergic and non-cholinergic laterodorsal tegmental neurons: Implications for the heightened adolescent susceptibility to nicotine addiction

Intrahippocampal infusion of the Ih blocker ZD7288 slows evoked theta rhythm and produces anxiolytic‐like effects in the elevated plus maze

Regulation of epileptiform discharges in rat neocortex by HCN channels

Contact Info

Product

Resources

About

Nicotine Blocks the Hyperpolarization-Activated CurrentI_hand Severely Impairs the Oscillatory Behavior of Oriens-Lacunosum Moleculare Interneurons

Intrahippocampal infusion of the I_h blocker ZD7288 slows evoked theta rhythm and produces anxiolytic‐like effects in the elevated plus maze