Synaptic structure and connectivity of serotonin terminals in the ventral tegmental area: potential sites for modulation of mesolimbic dopamine neurons

Bockstaele, Elisabeth J. Van; Cestari, Dean M.; Pickel, Virginia M.

doi:10.1016/0006-8993(94)91330-7

Cited by 119 publications

(79 citation statements)

References 58 publications

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“…In the substantia nigra and in the VTA, 5-HT 2C receptor expression is confined to GABAergic neurons making direct synaptic contact with dopaminergic cell bodies. Other immunoistochemical and electrophysiological studies [7,[122][123][124] have corroborated this piece of evidence suggesting an indirect control of dopaminergic transmission via 5-HT 2C receptors. Dense 5-HT 2C receptor labeling is found in about half of the neuronal population of the middle and caudal SNc and SNr.…”

Section: -Ht 2c Receptor Distribution and Cir-cuitry In Cnsmentioning

confidence: 58%

“…The dorsal raphe nucleus innervates the corpus striatum, the globus pallidus, the lateral septum nucleus and the amygdala, and provides most of the innervation of the prefrontal cortex. Serotonin-containing cell bodies of the raphe send projections to both dopaminergic cells in the ventrategmental area (VTA) and substantia nigra (SN), and to their terminal fields [5][6][7][8]. A comparison between the number of 5-HT terminals and the total number of axon terminals in the VTA reveals that the majority of these are serotonergic.…”

Section: Basic Anatomy Of 5-ht Systemmentioning

confidence: 99%

“…It is a pentamer consisting of five monomers, at least three different monomers (5-HT 3A/3B/3C ) have been found in the brain [22,23]. The 5-HT 4 , 5-HT 6 and 5-HT 7 receptors have all been demonstrated to be preferentially coupled to Gs and promote cAMP formation. However, the sequence dissimilarity justifies classification into different groups.…”

Section: -Ht Receptorsmentioning

confidence: 99%

“…Moreover, electron microscopy demonstrates the presence of synaptic contacts of [ 3 H]5-HT labeled terminals with both dopaminergic and non-dopaminergic dendrites in all subnuclei of the VTA and the SN pars compacta and reticulata [5,8,9]. These 5-HT axon terminals form many symmetric (inhibitory) contacts with non-dopaminergic and non-accumbens projecting neurons in the VTA, suggesting that 5-HT exerts an inhibitory influence on certain non-DA VTA neurons [7]. The DRN innervates, together with the MRN the ventral part of the hippocampus, the nucleus accumbens and various nuclei of the thalamus and the hippocampus [10][11][12].…”

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confidence: 99%

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Central Serotonin2C Receptor: From Physiology to Pathology

Giovanni¹,

Matteo²,

Pierucci³

et al. 2006

CTMC

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Since the 1950s, when serotonin (5-HT) was discovered in the mammalian central nervous system (CNS), an enormous amount of experimental evidence has revealed the pivotal role of this biogenic amine in a number of cognitive and behavioural functions. Although 5-HT is synthesized by a small group of neurons within the raphe nuclei of the brain stem, almost all parts of the CNS receive serotonergic projections. Furthermore, the importance of 5-HT modulation and the fine-tuning of its action is underlined by the large number of 5-HT binding sites found in the CNS. Hitherto, up to 15 different 5-HT receptors subtypes have been identified. This review was undertaken to summarize the work that has explored the pathophysiological role of one of these receptors, the 5-HT 2C receptor, that has been emerged as a prominent central serotonin receptor subtype. The physiology, pharmacology and anatomical distribution of the 5-HT 2C receptors in the CNS will be firstly reviewed. Finally, their potential involvement in the pathophysiology of depression, schizophrenia, Parkinson's disease and drug abuse will be also discussed.Keywords: Serotonergic receptors, Depression, Schizophrenia, Drug of abuse, selective 5-HT 2C drugs. BASIC ANATOMY OF 5-HT SYSTEMMore than fifty years have passed since Twarog and Page [1] isolated an indole, identified as serotonin (5-HT), in the mammalian brain. Subsequently, Brodie and colleagues [2] suggested that 5-HT might serve as a neurotransmitter in the central nervous system (CNS). The result was one of the most important discoveries in science, giving birth to a new branch of neuroscience [3]. Serotonin is one of the oldest biologically active compound on earth, found in a variety of plants and animals. In vertebrates, the majority of the neurons containing 5-HT are grouped in 9 nuclei named B1 to B9, located in the medial part of the brainstem, generically called the raphe nuclei [4] (Fig. 1). These midline clusters can be divided into two major groups. The caudal or inferior group, localized in the medulla, contains the three nuclei projecting essentially to the grey matter of the spinal cord: the nucleus raphe magnus (NRM, cell group B5), nucleus raphe obscurus (NRO, cell groups B1-B2-B3), and nucleus raphe pallidus (NRP, cell group B4). The rostral or superior group, situated in the pons/mesenchephalon, contains the dorsal raphe nucleus (DRN, cell groups B6 and B7) and the median raphe nucleus (MRN, cell group B8). These nuclei supply about 80% of the serotonergic innervation of the forebrain. Even if in many brain areas, the innervation coming from the two nuclei overlaps, in certain regions the innervation comes exclusively or prevalently from one nucleus only. For example, the dorsal hippocampus receives a serotonergic innervation only from MRN, other areas innervated preferentially from this nucleus are: the medial preoptic area, the suprachiasmatic nucleus, the olfactory bulb *Address correspondence to this author at the Istituto di Ricerche Farmacologiche "Mario Negri", Consor...

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Section: -Ht 2c Receptor Distribution and Cir-cuitry In Cnsmentioning

confidence: 58%

Section: Basic Anatomy Of 5-ht Systemmentioning

confidence: 99%

Section: -Ht Receptorsmentioning

confidence: 99%

mentioning

confidence: 99%

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Central Serotonin2C Receptor: From Physiology to Pathology

Giovanni¹,

Matteo²,

Pierucci³

et al. 2006

CTMC

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“…Furthermore, the distribution pattern of 5-HT 2C in this area showed a marked rostrocaudal labelling gradient, characterized by higher receptor densities in caudal regions of both nuclear subdivisions. Finally, with regard to cellular localization, receptor expression seems to be confined to GABAergic neurons but not to DAergic cell bodies (Van Bockstaele et al, 1994;Van Bockstaele and Pickel, 1995;Steffensen et al, 1998;Di Giovanni et al, 2001).…”

Section: Substantia Nigra and Globus Pallidusmentioning

confidence: 97%

Serotonin modulation of the basal ganglia circuitry: therapeutic implication for Parkinson's disease and other motor disorders

Matteo

Pierucci

Esposito

et al. 2008

Progress in Brain Research

138

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Several recent studies have emphasized a crucial role for the interactions between serotonergic and dopaminergic systems in movement control and the pathophysiology of basal ganglia. These observations are supported by anatomical evidence demonstrating large serotonergic innervation of all the basal ganglia nuclei. In fact, serotonergic terminals have been reported to make synaptic contacts with both substantia nigra dopamine-containing neurons and their terminal areas such as the striatum, the globus pallidus and the subthalamus. These brain areas contain a high concentration of serotonin (5-HT), with the substantia nigra pars reticulata receiving the greatest input. In this chapter, the distribution of different 5-HT receptor subtypes in the basal ganglia nuclei will be described. Furthermore, evidence demonstrating the serotonergic control of basal ganglia activity will be reviewed and the contribution of the different 5-HT receptor subtypes examined. The new avenues that the increasing knowledge of 5-HT in motor control has opened for exploring the pathophysiology and pharmacology of Parkinson's disease and other movement disorders will be discussed. It is clear that these avenues will be fruitful, despite the disappointing results so far obtained by clinical studies with selective 5-HT ligands. Nevertheless, these studies have led to a great increase in the attention given to the neurotransmitters of the basal ganglia and their connections.

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Synaptic innervation of midbrain dopaminergic neurons by glutamate-enriched terminals in the squirrel monkey

1996

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The excitatory amino acid, glutamate, has long been thought to be a transmitter that plays a major role in the control of the firing pattern of midbrain dopaminergic neurons. The present study was aimed at elucidating the anatomical substrate that underlies the functional interaction between glutamatergic afferents and midbrain dopaminergic neurons in the squirrel monkey. To do this, we combined preembedding immunocytochemistry for tyrosine hydroxylase and calbindin D-28k with postembedding immunostaining for glutamate. On the basis of their ultrastructural features, three types (so-called types I, II, and III) of glutamate-enriched terminals were found to form asymmetric synapses with dendrites and perikarya of midbrain dopaminergic neurons. The type I terminals accounted for more than 70% of the total population of glutamate-enriched boutons in contact with dopaminergic cells in the dorsal and ventral tiers of the substantia nigra pars compacta as well as in the ventral tegmental area, whereas 5-20% of the glutamatergic synapses with dopaminergic neurons involved the two other types of terminals. The major finding of our study is that the glutamate-enriched boutons were involved in 70% of the axodendritic synapses in the ventral tegmental area. In contrast, less than 40% of the boutons in contact with dopaminergic dendrites were immunoreactive for glutamate in the dorsal and ventral tiers of the substantia nigra pars compacta. Approximately 50% of the terminals in contact with the perikarya of the different populations of midbrain dopaminergic neurons displayed glutamate immunoreactivity. In conclusion, our findings provide the first evidence that glutamate-enriched terminals form synapses with midbrain dopaminergic neurons in primates. The fact that the proportion of glutamatergic boutons in contact with dopaminergic cells is higher in the ventral tegmental area than in the substantia nigra pars compacta suggests that the different groups of midbrain dopaminergic neurons are modulated differently by extrinsic glutamatergic afferents in primates.

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Synaptic structure and connectivity of serotonin terminals in the ventral tegmental area: potential sites for modulation of mesolimbic dopamine neurons

Cited by 119 publications

References 58 publications

Central Serotonin2C Receptor: From Physiology to Pathology

Central Serotonin2C Receptor: From Physiology to Pathology

Serotonin modulation of the basal ganglia circuitry: therapeutic implication for Parkinson's disease and other motor disorders

Synaptic innervation of midbrain dopaminergic neurons by glutamate-enriched terminals in the squirrel monkey

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