Glutamatergic projection from the nucleus incertus to the septohippocampal system

Cervera‐Ferri, Ana; Rahmani, Yasamin; Martínez-Bellver, Sergio; Teruel‐Martí, Vicent; Martínez‐Ricós, Joana

doi:10.1016/j.neulet.2012.04.014

Cited by 24 publications

(25 citation statements)

References 34 publications

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“…The contribution of the NI as a relevant node for the integration of the arousal, stress and cognitive systems has already been postulated (Goto et al ., ; Olucha‐Bordonau et al ., ; Nuñez et al ., ; Teruel‐Martí et al ., ; Banerjee et al ., ; Cervera‐Ferri et al ., , ; Ryan et al ., ; Ma et al ., ). Accordingly, the NI exhibits the highest expression in the tegmentum for the CRH‐R1 receptor for CRH (Potter et al ., , ; Chalmers et al ., ) and becomes activated after intraventricular infusion of CRH (Bittencourt & Sawchenko, ), as well as in stressful situations (Banerjee et al ., ).…”

Section: Discussionmentioning

confidence: 99%

“…In their experiments, all these neurons expressed the CRH‐R1 and exhibited phase coupling as a response to the CRH infusion, while relaxin‐3‐negative neurons were not locked to the hippocampal theta. Some of the NI neurons that project to the septal complex contain the vesicular transporter of glutamate VGLUT‐2 (Cervera‐Ferri et al ., ), although most NI neurons are GABAergic, expressing glutamic acid decarboxylase 65/67 (GAD) and either, or both, the calcium‐binding proteins calbindin and calretinin, and also cholinoceptive but non‐cholinergic (Olucha‐Bordonau et al ., ). Also, the majority of these neurons project to the medial septum (Cervera‐Ferri et al ., ).…”

Section: Discussionmentioning

confidence: 99%

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Regular theta‐firing neurons in the nucleus incertus during sustained hippocampal activation

Martínez-Bellver

Cervera‐Ferri

Martínez‐Ricós

et al. 2015

Eur J of Neuroscience

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This paper describes the existence of theta-coupled neuronal activity in the nucleus incertus (NI). Theta rhythm is relevant for cognitive processes such as spatial navigation and memory processing, and can be recorded in a number of structures related to the hippocampal activation including the NI. Strong evidence supports the role of this tegmental nucleus in neural circuits integrating behavioural activation with the hippocampal theta rhythm. Theta oscillations have been recorded in the local field potential of the NI, highly coupled to the hippocampal waves, although no rhythmical activity has been reported in neurons of this nucleus. The present work analyses the neuronal activity in the NI in conditions leading to sustained hippocampal theta in the urethane-anaesthetised rat, in order to test whether such activation elicits a differential firing pattern. Wavelet analysis has been used to better define the neuronal activity already described in the nucleus, i.e., non-rhythmical neurons firing at theta frequency (type I neurons) and fast-firing rhythmical neurons (type II). However, the most remarkable finding was that sustained stimulation activated regular-theta neurons (type III), which were almost silent in baseline conditions and have not previously been reported. Thus, we describe the electrophysiological properties of type III neurons, focusing on their coupling to the hippocampal theta. Their spike rate, regularity and phase locking to the oscillations increased at the beginning of the stimulation, suggesting a role in the activation or reset of the oscillation. Further research is needed to address the specific contribution of these neurons to the entire circuit.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Regular theta‐firing neurons in the nucleus incertus during sustained hippocampal activation

Martínez-Bellver

Cervera‐Ferri

Martínez‐Ricós

et al. 2015

Eur J of Neuroscience

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“…Relaxin-3 containing neurons in these areas innervate a broad range of target forebrain regions rich in RXFP3. NI relaxin-3 neurons are predominately GABAergic (Ma et al, 2007; Cervera-Ferri et al, 2012), and it is likely relaxin-3 signaling confers complimentary inhibitory effects to the primary transmitter, as in cell-based studies RXFP3 activation is linked to G i/o and reduces cAMP accumulation (van der Westhuizen et al, 2007). In recent electrophysiological experiments, however, RXFP3 activation was able to hyperpolarize or depolarize presumed RXFP3-positive neurons within the rat intergeniculate leaflet (Blasiak et al, 2013), suggesting the effect of receptor activation or inhibition may vary with the neurochemical phenotype and connectivity of the target neuron, as described for other peptides.…”

Section: The Neuropeptide Relaxin-3 and Its Receptor Rxfp3mentioning

confidence: 99%

“…In particular, the medial septum has been termed the hippocampal theta rhythm “pace-maker” and contains populations of cholinergic and GABAergic neurons which provide alternating synchronous excitatory/inhibitory input to reciprocally connected hippocampal neurons (Vertes and Kocsis, 1997; Wang, 2002; Hangya et al, 2009). The NI sits adjacent to, and is strongly interconnected with, the RPO, median raphé and IPN, and efferent relaxin-3-positive projections innervate the hippocampus and the major nodes of the septohippocampal pathway (Ma et al, 2007; Teruel-Marti et al, 2008; Smith et al, 2010; Cervera-Ferri et al, 2012), including the medial septum which displays a high density of relaxin-3 immunoreactive fibers and terminals which make synaptic contacts with hippocampal-projecting cholinergic and GABAergic neurons in the rat (Olucha-Bordonau et al, 2012). …”

Section: Relaxin-3/rxfp3 Signaling: a Novel Target For The Treatment mentioning

confidence: 99%

“…Simultaneous recording of hippocampal and NI field potentials (Cervera-Ferri et al, 2011) and electrophysiological recording of NI neurons (Ma et al, 2013) have also revealed that these two structures are “theta-synchronized” and individual neurons display coherent firing. Although it is likely that these actions are primarily conferred by GABA (or to a much lesser extent, glutamate) transmission of these septohippocampal-projecting NI neurons (Ma et al, 2007; Cervera-Ferri et al, 2012), relaxin-3/RXFP3 signaling nonetheless appears capable of contributing to this functional effect. Our laboratory has shown that local infusion of an RXFP3 agonist into the medial septum of anesthetized rats promotes hippocampal theta rhythm, while medial septum infusion of an RXFP3 antagonist in conscious rats inhibits hippocampal theta and theta-dependent spatial memory measured in a spontaneous alternation task (Ma et al, 2009a).…”

Section: Relaxin-3/rxfp3 Signaling: a Novel Target For The Treatment mentioning

confidence: 99%

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Relaxin-3/RXFP3 networks: an emerging target for the treatment of depression and other neuropsychiatric diseases?

et al. 2014

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Animal and clinical studies of gene-environment interactions have helped elucidate the mechanisms involved in the pathophysiology of several mental illnesses including anxiety, depression, and schizophrenia; and have led to the discovery of improved treatments. The study of neuropeptides and their receptors is a parallel frontier of neuropsychopharmacology research and has revealed the involvement of several peptide systems in mental illnesses and identified novel targets for their treatment. Relaxin-3 is a newly discovered neuropeptide that binds, and activates the G-protein coupled receptor, RXFP3. Existing anatomical and functional evidence suggests relaxin-3 is an arousal transmitter which is highly responsive to environmental stimuli, particularly neurogenic stressors, and in turn modulates behavioral responses to these stressors and alters key neural processes, including hippocampal theta rhythm and associated learning and memory. Here, we review published experimental data on relaxin-3/RXFP3 systems in rodents, and attempt to highlight aspects that are relevant and/or potentially translatable to the etiology and treatment of major depression and anxiety. Evidence pertinent to autism spectrum and metabolism/eating disorders, or related psychiatric conditions, is also discussed. We also nominate some key experimental studies required to better establish the therapeutic potential of this intriguing neuromodulatory signaling system, including an examination of the impact of RXFP3 agonists and antagonists on the overall activity of distinct or common neural substrates and circuitry that are identified as dysfunctional in these debilitating brain diseases.

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Nucleus incertus promotes cortical desynchronization and behavioral arousal

Allocca

Ong-Palsson

et al. 2016

Brain Struct Funct

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Arousal and vigilance are essential for survival and relevant regulatory neural circuits lie within the brainstem, hypothalamus and forebrain. The nucleus incertus (NI) is a distinct site within the pontine periventricular gray, containing a substantial population of GABAergic neurons with long-range, ascending projections. Existing neuroanatomical data and functional studies in anesthetized rats, suggest the NI is a central component of a midline behavioral control network well positioned to modulate arousal, vigilance and exploratory navigation, yet none of these roles have been established experimentally. We used a chemogenetic approach-clozapine-N-oxide (CNO) activation of virally delivered excitatory hM3Dq-DREADDs-to activate the NI in rats and examined the behavioral and physiological effects, relative to effects in naïve rats and appropriate viral-treated controls. hM3Dq activation by CNO resulted in long-lasting depolarization of NI neurons with action potentials, in vitro. Peripheral injection of CNO significantly increased c-Fos immunoreactivity in the NI and promoted cortical electroencephalograph (EEG) desynchronization. These brain changes were associated with heightened arousal, and increased locomotor activity in the homecage and in a novel environment. Furthermore, NI activation altered responses in a fear conditioning paradigm, reflected by increased head-scanning, vigilant behaviors during conditioned fear recall. These findings provide direct evidence that the NI promotes general arousal via a broad behavioral activation circuit and support early hypotheses, based on its connectivity, that the NI is a modulator of cognition and attention, and emotional and motivated behaviors.

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Glutamatergic projection from the nucleus incertus to the septohippocampal system

Cited by 24 publications

References 34 publications

Regular theta‐firing neurons in the nucleus incertus during sustained hippocampal activation

Regular theta‐firing neurons in the nucleus incertus during sustained hippocampal activation

Relaxin-3/RXFP3 networks: an emerging target for the treatment of depression and other neuropsychiatric diseases?

Nucleus incertus promotes cortical desynchronization and behavioral arousal

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