Simultaneous projections from prefrontal cortex to dopaminergic and serotonergic nuclei

Vazquez, Pablo Raul Ruisenor; Celada, Pau; Cortés, Roser; Artigas, Francesc

doi:10.1017/s1461145710000349

Cited by 42 publications

(26 citation statements)

References 76 publications

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“…DAVID categorized these genes into those controlling lipid metabolism, coagulation, hormonal activity, immunological function, and amine synthesis, with significant interactions among each categorized gene. The PFC is a projection area for dopaminergic and serotonergic neurons and modulates these systems [43–45]. For instance, Tryptophan 2,3-dioxygenase (Tdo2) was categorized as an amine synthesis molecule by DAVID in this study, and it is a rate-limiting enzyme expressed in the pathway from tryptophan to kynurenine, which is an alternative pathway to the tryptophan-serotonin pathway [15].…”

Section: Discussionmentioning

confidence: 99%

Hepatocyte Nuclear Factor 4 Alpha Is a Key Factor Related to Depression and Physiological Homeostasis in the Mouse Brain

et al. 2015

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Major depressive disorder (MDD) is a common psychiatric disorder that involves marked disabilities in global functioning, anorexia, and severe medical comorbidities. MDD is associated with not only psychological and sociocultural problems, but also pervasive physical dysfunctions such as metabolic, neurobiological and immunological abnormalities. Nevertheless, the mechanisms underlying the interactions between these factors have yet to be determined in detail. The aim of the present study was to identify the molecular mechanisms responsible for the interactions between MDD and dysregulation of physiological homeostasis, including immunological function as well as lipid metabolism, coagulation, and hormonal activity in the brain. We generated depression-like behavior in mice using chronic mild stress (CMS) as a model of depression. We compared the gene expression profiles in the prefrontal cortex (PFC) of CMS and control mice using microarrays. We subsequently categorized genes using two web-based bioinformatics applications: Ingenuity Pathway Analysis and The Database for Annotation, Visualization, and Integrated Discovery. We then confirmed significant group-differences by analyzing mRNA and protein expression levels not only in the PFC, but also in the thalamus and hippocampus. These web tools revealed that hepatocyte nuclear factor 4 alpha (Hnf4a) may exert direct effects on various genes specifically associated with amine synthesis, such as genes involved in serotonin metabolism and related immunological functions. Moreover, these genes may influence lipid metabolism, coagulation, and hormonal activity. We also confirmed the significant effects of Hnf4a on both mRNA and protein expression levels in the brain. These results suggest that Hnf4a may have a critical influence on physiological homeostasis under depressive states, and may be associated with the mechanisms responsible for the interactions between MDD and the dysregulation of physiological homeostasis in humans.

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Section: Discussionmentioning

confidence: 99%

Hepatocyte Nuclear Factor 4 Alpha Is a Key Factor Related to Depression and Physiological Homeostasis in the Mouse Brain

et al. 2015

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“…Lower abundances are found in ventro-caudal part of CA3, medial mammillary nucleus, striatum (dorsal and ventral) and several brainstem nuclei (Pompeiano et al, 1994; Burnet et al, 1995; López-Giménez et al, 1998). Interestingly, pyramidal neurons in the rat PFC that simultaneously project to the ventral tegmental area and the dorsal raphe nucleus express 5-HT 2A receptors (Vázquez-Borsetti et al, 2009, 2011). This reveals a close anatomical interaction or “loop” between frontal areas and dopamine and serotonin neurons of the brainstem, as found in several electrophysiological studies (Thierry et al, 1979, 1983; Tong et al, 1996; Hajós et al, 1998; Celada et al, 2001; Martín-Ruiz et al, 2001).…”

Section: The Cortical 5-ht System: Receptor Localizationmentioning

confidence: 99%

“…The neocortex contains low levels of the 5-HT 4 receptor and its encoding mRNA, as assessed by autoradiography and in situ hybridization, respectively (Waeber et al, 1994; Vilaró et al, 1996, 2005). However, studies using single-cell RT-PCR technique reported that ~60% of pyramidal neurons recorded in the PFC contain the 5-HT 4 receptor transcript (Feng et al, 2001), and overexpression of 5-HT 4 in the mPFC increases DRN 5-HT activity (Lucas et al, 2005) likely through descending excitatory axons reaching the DR (Celada et al, 2001; Vázquez-Borsetti et al, 2011). …”

Section: The Cortical 5-ht System: Receptor Localizationmentioning

confidence: 99%

Serotonin modulation of cortical neurons and networks

Celada¹,

Puig²,

Artigas³

2013

Front. Integr. Neurosci.

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342

283

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The serotonergic pathways originating in the dorsal and median raphe nuclei (DR and MnR, respectively) are critically involved in cortical function. Serotonin (5-HT), acting on postsynaptic and presynaptic receptors, is involved in cognition, mood, impulse control and motor functions by (1) modulating the activity of different neuronal types, and (2) varying the release of other neurotransmitters, such as glutamate, GABA, acetylcholine and dopamine. Also, 5-HT seems to play an important role in cortical development. Of all cortical regions, the frontal lobe is the area most enriched in serotonergic axons and 5-HT receptors. 5-HT and selective receptor agonists modulate the excitability of cortical neurons and their discharge rate through the activation of several receptor subtypes, of which the 5-HT1A, 5-HT1B, 5-HT2A, and 5-HT3 subtypes play a major role. Little is known, however, on the role of other excitatory receptors moderately expressed in cortical areas, such as 5-HT2C, 5-HT4, 5-HT6, and 5-HT7. In vitro and in vivo studies suggest that 5-HT1A and 5-HT2A receptors are key players and exert opposite effects on the activity of pyramidal neurons in the medial prefrontal cortex (mPFC). The activation of 5-HT1A receptors in mPFC hyperpolarizes pyramidal neurons whereas that of 5-HT2A receptors results in neuronal depolarization, reduction of the afterhyperpolarization and increase of excitatory postsynaptic currents (EPSCs) and of discharge rate. 5-HT can also stimulate excitatory (5-HT2A and 5-HT3) and inhibitory (5-HT1A) receptors in GABA interneurons to modulate synaptic GABA inputs onto pyramidal neurons. Likewise, the pharmacological manipulation of various 5-HT receptors alters oscillatory activity in PFC, suggesting that 5-HT is also involved in the control of cortical network activity. A better understanding of the actions of 5-HT in PFC may help to develop treatments for mood and cognitive disorders associated with an abnormal function of the frontal lobe.

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“…A small population of PFC neurons may be responsible for this output, as individual neurons within the PFC innervate more than one neuromodulatory center. For instance, a small population of PFC neurons project to both the RN and the VTA (Gabbott et al, 2005; Vázquez-Borsetti et al, 2009, 2011). Similarly, a subset of PFC neurons project to both RN and LC (Lee et al, 2005).…”

Section: Neuromodulation and The Prefrontal Cortexmentioning

confidence: 99%

Subcircuit-specific neuromodulation in the prefrontal cortex

Dembrow

Johnston

2014

Front. Neural Circuits

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During goal-directed behavior, the prefrontal cortex (PFC) exerts top-down control over numerous cortical and subcortical regions. PFC dysfunction has been linked to many disorders that involve deficits in cognitive performance, attention, motivation, and/or impulse control. A common theme among these disorders is that neuromodulation of the PFC is disrupted. Anatomically, the PFC is reciprocally connected with virtually all neuromodulatory centers. Recent studies of PFC neurons, both in vivo and ex vivo, have found that subpopulations of prefrontal projection neurons can be segregated into distinct subcircuits based on their long-range projection targets. These subpopulations differ in their connectivity, intrinsic properties, and responses to neuromodulators. In this review we outline the evidence for subcircuit-specific neuromodulation in the PFC, and describe some of the functional consequences of selective neuromodulation on behavioral states during goal-directed behavior.

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Simultaneous projections from prefrontal cortex to dopaminergic and serotonergic nuclei

Cited by 42 publications

References 76 publications

Hepatocyte Nuclear Factor 4 Alpha Is a Key Factor Related to Depression and Physiological Homeostasis in the Mouse Brain

Hepatocyte Nuclear Factor 4 Alpha Is a Key Factor Related to Depression and Physiological Homeostasis in the Mouse Brain

Serotonin modulation of cortical neurons and networks

Subcircuit-specific neuromodulation in the prefrontal cortex

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