Effects of ICV administration of neurotensin and analogs on EEG in rats

Castel, Marie-Noëlle; Stutzmann, Jean‐Marie; Lucas, M.; Lafforgue, Joséphine; Blanchard, Jean‐Charles

doi:10.1016/0196-9781(89)90083-1

Cited by 18 publications

(10 citation statements)

References 26 publications

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“…By inducing depolarization and G, decrease, and by blocking both the TOR and the sAHP, NT can efficiently increase the responsiveness and activity of BF cholinergic cells. This is compatible with a role ofNT in promoting cortical activation (Caste1 et al, 1989). However, the depolarizing effect of NT is accompanied by an enhancement of the BF cholinergic neurons oscillatory bursting.…”

Section: Nt Internalizationsupporting

confidence: 54%

“…Indeed, limbic theta rhythmicity accompanies neocortical (apparent) desynchronization (Green and Arduini, 1954;Vanderwolf, 1969) and both processes are controlled by BF cholinergic influences (Stewart et al, 1984;Bland, 1986;Casamenti et al, 1986;BuzsZlki et al, 1988;Stewart and Fox, 1990;Metherate et al, 1992). On the other hand, it may be that the awakening effect reported after intracerebroventricular injections of NT (Caste1 et al, 1989) results from NT actions outside the BF. If so, an important role of the NT-induced rhythmic bursts may be that of modulating slow forebrain rhythms.…”

Section: Nt Internalizationmentioning

confidence: 97%

“…In freely behaving rats, intracerebroventricular administration of NT has been shown to produce an awakening effect and an increase in limbic theta rhythm activity (Caste1 et al, 1989) that is known to accompany neocortical desynchronization (Green and Arduini, 1954;Vanderwolf, 1969Vanderwolf, , 1975Vanderwolf, , 1988. Since the cholinergic neurons of the BF play a crucial role both in limbic theta rhythm generation and neocortical desynchronization (Robinson et al, 1977;Bland, 1986;Buzsaki et al, 1988;Stewart and Fox, 1990), the above effects may have resulted from the actions of NT on the BF cholinergic cells.…”

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confidence: 99%

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Neurotensin promotes oscillatory bursting behavior and is internalized in basal forebrain cholinergic neurons

1994

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Cholinergic neurons of the basal forebrain magnocellular complex (BF) constitute the primary source of ACh to the cerebral cortex and are thought to be instrumental in mediating cortical activation and plasticity. Recent light and electron microscopic studies have revealed a selective association of receptors for the neuropeptide neurotensin (NT) with BF cholinergic neurons, suggesting that this peptide may be playing a key role in the control of BF cholinergic function. In the present study, we have investigated by means of intracellular recording in guinea pig brain slices the neuromodulatory actions of NT on the intrinsic excitability of BF cholinergic neurons that were identified electrophysiologically by their low-threshold discharge, slow afterhyperpolarization, and transient outward rectification (TOR). In all cholinergic neurons tested (n = 39), bath application of NT (20–200 nM for 1–4 min) produced, via a direct mechanism, a membrane potential depolarization associated with a decrease in apparent input conductance. Most significantly, NT led to the emergence of a very prominent slow rhythmic bursting pattern that could shape into complex spindle-like sequences that were intrinsically generated by the cholinergic cells. These NT actions were also accompanied by a reduction of both the slow afterhyperpolarization and TOR. Bursting oscillations relied on the activation of Ca2+ conductances as opposed to Na+ conductances, since they were absent during Ca(2+)-conductance block with Mn2+, but still occurred in the presence of the Na(+)- channel blocker TTX. NT actions were specific, since they could be reproduced by application of the active (NT 8–13) but not of the inactive (NT 1–8) fragment of the peptide. Identification of the BF cholinergic neurons as direct NT targets was further provided by confocal laser scanning microscopic demonstration of internalization of a fluoresceinylated derivative of NT (fluo-NT) within biocytin-filled, electrophysiologically identified cholinergic neurons. The results demonstrate the electrophysiological functionality of NT receptors on BF cholinergic neurons and the existence of a receptor-mediated internalization of NT in these cells. They also suggest that the peptide is an important player in the control of BF function and, in particular, in the generation of forebrain network oscillations.

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Section: Nt Internalizationsupporting

confidence: 54%

Section: Nt Internalizationmentioning

confidence: 97%

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confidence: 99%

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Neurotensin promotes oscillatory bursting behavior and is internalized in basal forebrain cholinergic neurons

1994

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“…Induction of activity was also shown to occur in another study using intracerebroventricular administration of NT (Castel et al, 1989). The promotion of activity in both cases may be caused by the stimulation of rhythmic burst discharge of basalocortical cholinergic neurons and thus rhythmic release of ACh from their terminals in the cortex.…”

Section: Discussionmentioning

confidence: 89%

Neurotensin-Induced Bursting of Cholinergic Basal Forebrain Neurons Promotes γ and θ Cortical Activity Together with Waking and Paradoxical Sleep

Cape

Manns²,

Alonso³

et al. 2000

J. Neurosci.

117

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Cholinergic basal forebrain neurons have long been thought to play an important role in cortical activation and behavioral state, yet the precise way in which they influence these processes has yet to be fully understood. Here, we have examined the effects on the electroencephalogram (EEG) and sleep-wake state of basal forebrain administration of neurotensin (NT), a neuropeptide that has been shown in vitro to potently and selectively modulate the cholinergic cells. Microinjection of (0.1-3.0 mM) NT into the basal forebrain of freely moving, naturally waking-sleeping rats produced a dose-dependent decrease in ␦ (ϳ1-4 Hz) and increase in both (ϳ4-9 Hz) and high-frequency ␥ activity (30-60 Hz) across cortical, areas with no increase in the electromyogram. These EEG changes were accompanied by concomitant decreases in slow wave sleep (SWS) and transitional SWS (tSWS), increases in wake, and most remarkably, increases in paradoxical sleep (PS) and transitional PS (tPS), despite the virtual absence of SWS. The effects were attributed to direct action on cholinergic neurons as evidenced by selective internalization of a fluorescent ligand, Fluo-NT, in choline acetyltransferase (ChAT)-immunoreactive cells and stimulation by NT of bursting discharge in juxtacellularly recorded, Neurobiotin-labeled, ChATimmunoreactive neurons. We conclude that NT-induced rhythmic bursting of cholinergic basal forebrain neurons stimulates rhythmic oscillations and ␥ across the cerebral cortex. With the selective action of NT on the cholinergic cells, their bursting discharge promotes and ␥ independent of motor activity and thereby also stimulates and enhances PS.

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“…Doses were chosen based on previous i.c.v. studies of the behavioral effects of NT in mice and rats (Levine et al, 1983, Meisenberg and Simmons, 1985, Castel et al, 1989, Rompre, 1995, Lambert et al, 1996). …”

Section: Methodsmentioning

confidence: 99%

Neurotensin inversely modulates maternal aggression

et al. 2009

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Neurotensin (NT) is a versatile neuropeptide involved in analgesia, hypothermia, and schizophrenia. Although NT is released from and acts upon brain regions involved in social behaviors, it has not been linked to a social behavior. We previously selected mice for high maternal aggression (maternal defense), an important social behavior that protects offspring, and found significantly lower NT expression in the CNS of highly protective females. Our current study directly tested NT's role in maternal defense. Intracerebroventricular (icv) injections of NT significantly impaired defense in terms of time aggressive and number of attacks at all doses tested (0.05, 0.1, 1.0, and 3.0 μg). Other maternal behaviors, including pup retrieval, were unaltered following NT injections (0.05 μg) relative to vehicle, suggesting specificity of NT action on defense. Further, icv injections of the NT receptor 1 (NT1) antagonist, SR 48692 (30 μg), significantly elevated maternal aggression in terms of time aggressive and attack number. To understand where NT may regulate aggression, we examined Fos following injection of either 0.1 μg NT or vehicle. 13 of 26 brain regions examined exhibited significant Fos increases with NT, including regions expressing NT1 and previously implicated in maternal aggression, such as lateral septum, bed nucleus of stria terminalis, paraventricular nucleus, and central amygdala. Together, our results indicate that NT inversely regulates maternal aggression and provide the first direct evidence that lowering of NT signaling can be a mechanism for maternal aggression. To our knowledge, this is the first study to directly link NT to a social behavior. Keywordsfight; flight; maternal aggression; maternal defense; lactation; mice Neurotensin (NT) is a versatile neuropeptide that plays a role in analgesia (Dubuc et al., 1999, Sarret et al., 2005, hypothermia (Nemeroff et al., 1977, Martin et al., 1980, Remaury et al., 2002, and schizophrenia (Nemeroff, 1986, Kinkead and. NT acts most commonly via either NT receptor 1 (NT1) or receptor 2 (NT2) (Tanaka et al., 1990, Richard et al., 2001, Sarret et al., 2002, but it can also act via NT receptor 3, a sortilin receptor that internalizes the ligand (Mazella, 2001). NT and its receptors are highly conserved among mammals (Dobner, 2005). Although NT is expressed in and acts upon a number of areas critical for social behavior, including nucleus accumbens, lateral septum (LS), bed nucleus of stria terminalis (BNST), preoptic area, amygdala, and periaqueductal gray (Boudin et al., 1996, Binder et al., 2001a, Sarret et al., 2003, it has received almost no research attention regarding Corresponding Author: Stephen C. Gammie, 1117 W. Johnson St., Madison, WI 53706, Telephone: (608) Fax: (608) 262-9083, E-mail: scgammie@wisc.edu. Section Editor: Joan Morrell Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscrip...

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Effects of ICV administration of neurotensin and analogs on EEG in rats

Cited by 18 publications

References 26 publications

Neurotensin promotes oscillatory bursting behavior and is internalized in basal forebrain cholinergic neurons

Neurotensin promotes oscillatory bursting behavior and is internalized in basal forebrain cholinergic neurons

Neurotensin-Induced Bursting of Cholinergic Basal Forebrain Neurons Promotes γ and θ Cortical Activity Together with Waking and Paradoxical Sleep

Neurotensin inversely modulates maternal aggression

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