The projections of the ventral tegmental area and adjacent regions: A combined fluorescent retrograde tracer and immunofluorescence study in the rat

“Age (r: 0.46, P ¼ 3E202) and pH (r: 20.76, P ¼ 5E202) correlated with modest significance with SLC1A3 transcription, indicating that unlike in the human PFC (44), this transporter is not sensitive to heavy smoking or chronic alcohol abuse in the VTA.”

“The VTA contains predominantly dopaminergic neurons (65%), but GABAergic neurons (~30%) and glutamate neurons (~5%) have also been identified in this region (Swanson, 1982; Margolis et al., 2006; Nair-Roberts et al., 2008; Yamaguchi et al., 2011).”

“Alternatively, contralateral Fos expression may have been induced polysynaptically via VTA fibres known to traverse frontally to the other hemisphere.(1,5,8,43)”

“The adult SVZ and DG also receive dopaminergic input from the substantia nigra and ventral tegmental area (Swanson 1982).”

“…forebrain, basal amygdala, ventral hippocampus, and medial prefrontal cortex (Fallon et al., 1978; Fallon and Moore, 1978; Beckstead et al., 1979; Swanson, 1982; Lindvall and Björkland, 1983; Phillipson and Griffiths, 1985; Fallon and Loughlin, 1985, 1995; Fallon, 1988; DelFava et al., 2007),…”

“Some studies, for example, that by Swanson (1982), did not divide the VTA and use it as a synonym for the A10 group; others adopted different subdivisions (Deutch et al., 1988; German and Manaye, 1993; Giolli et al.,1985; Halliday and Tork, 1986).”

“The hypothalamus, thalamus and amygdala, which were other brain regions showing a negative correlation with BMI, receive dopaminergic [32–38] and serotonergic innervations [39– 41] and thus their decreased activation in obese subjects could also reflect decreased dopaminergic and serotonergic neurotransmission in obes…”

“…and ventral CA1 ¢eld), amgydala (viz., amygdalohippocampal area, amygdalopiriform transition area and basolateral amygdaloid nucleus), lateral hypothalamic area and ventral tegmental area (Swanson, 1981, 1982; McDonald, 1987, 1991; Conde et al., 1990, 1995; Berendse and Groenewegen, 1991; ).”

“…(Van Bockstaele and Pickel, 1995), prefrontal cortex (PFC) (Carr and Sesack, 2000), amygdala (Rosenkrantz and Grace, 2002), hypothalamus and MPOA (Swanson, 1982; Miller and Lonstein, 2006), ventral pallidum (Fields et al., 2007) and lateral habenula (Swanson, 1982), which may contribute…”

“The VTApb and VTApn subdivisions were defined according to Fallon and Loughlin (1995), Paxinos and Watson (1986), and Swanson (1982).”

“. Since VTA projections rarely collateralize between target regions”

“…our observation that the antipsychotic drugs have lower potency for D3 receptors in LOB, which lacks dopaminergic innervation (Beckstead et al, 1979; Swanson, 1982), than for D2 receptors in STR, nor can it explain the inverse regional trend between antipsychotic occupancy and SB277011 occupancy.”

“Since about 65% of cells in the rat VTA are dopaminergic (Swanson 1982), it seems unlikely that a selective increase in AMPA receptor subunit expression within DA neurons would be completely masked by the signal from non-DA cells.”

“…reproduction of this article is prohibited. forebrain areas implicated in fear and anxiety, such as the amygdala, hippocampus, nucleus accumbens, and prefrontal cortex are innervated by dopaminergic fibers originating in the VTA (Swanson, 1982; Oades and Halliday, 1987; Li et al., 2009).”

“The major source of DA neurons in the PFC is a ventral tegmental area (VTA) [19], which contains GABAA Fig.”

“neurons (Fallon and Moore, 1978; Swanson, 1982; Margolis et al., 2006) but also GABAergic and glutamatergic neurons are”

“Dopamine neurons comprise the largest neuronal population within the VTA, as tyrosine hydroxylase (TH), the rate-limiting enzyme for dopamine synthesis, is found in ~60% of VTA neurons (46, 49).”

“Previous studies have demonstrated that the VTA and the substantia nigra project DAergic neurons to the dentate gyrus of the hippocampus through mesolimbic pathway (Swanson, 1982).”

“However, the VTA-LC connection seems to be largely non-dopaminergic ( Swanson, 1982 ) although sparse immunoreactive fibers have been detected in the LC stained with an antiserum raised against DA (Geffard et al., 1984).”

“, 2008), which give rise to DA in the NAc (Bjorklund & Lindvall, 1984; Fallón & Moore, 1978; Phillipson & Grifflths, 1985; Swanson, 1982).”

“At least some GABAergic (presumably secondary) neurons in the rodent VTA project to striatum or to prefrontal cortex (Carr and Sesack 2000; Swanson 1982; Van Bockstaele and Pickel 1995).”

“The differential functions of DA subpopulations are mediated by different projections (Swanson, 1982; Yetnikoff et al., 2014; Saunders et al., 2018).”

“…goal-directed behaviors as well as in learning and memory (Ikemoto & Panksepp, 1999; Carelli, 2004) and consists of DA producing neurons in the ventral tegmental area (VTA) that project to and release DA within various target brain regions, including the nucleus accumbens (NAcc) (Swanson, 1982).”

“We found that adult VTA NtsR1 neurons comprise 70% of VTA DA neurons and project primarily to the NA, OFT, and IPAC, but not to other efferent targets of VTA NA neurons such as the PFC or hippocampus (Swanson, 1982).”

“The VTA has most often been delineated in coronal sections as the group of cells medial to the substantia nigra (SN) and medial lemniscus sometimes including the dopaminergic midline nuclei [Oades and Halliday, 1987] and sometimes excluding these nuclei [see Ikemoto, 2007, for a review of VTA delineation and nomenclat…”

“The mesocortical pathway is comprised of at least two distinct neuronal populations, one of which is the dopamine-containing cells in the VTA that project to the mPFC (Swanson, 1982; Oades and Halliday, 1987).”

“Anatomical studies using retrograde-tracer indicated that NAc receives dopaminergic projections from both pVTA and aVTA, but that those from pVTA dominate (Ikemoto, 2007; Olson et al., 2005; Swanson, 1982).”

“the ventral tegmental area (VTA), but it extends to other regions including dorsal raphe, caudal linear nucleus of the raphe (CLi), rostral linear nucleus of the raphe (RLi), interfascicular nucleus (IF), and medial supramammillary nucleus (Phillipson, 1979; Swanson, 1982).”

“If VTA dopamine neurons signal negative prediction error, then what regions may utilize error to reduce the associative strength of cue-shock associations? One candidate is the hippocampus, which receives modest VTA inputs (Swanson, 1982).”

“…(TM) located in the posterior hypothalamus project to numerous regions of the brain, including the neocortex, hippocam- pal formation, amygdala, basal ganglia, thalamus, cerebellum, and various parts of the brain stem (Inagaki et al. 1988; Panula et al. 1989; Steinbusch et al. 1986; Swanson 1982).”

“The focus on the amygdala and nucleus accumbens is of particular relevance as VTA dopaminergic neurons have strong efferent projections to these areas (Swanson, 1982).”

“In addition to dopaminergic afferents from the ventral tegmental area (Swanson 1982), NAS receives glutamatergic inputs from various brain areas, including the prefrontal cortex, amygdala, hippocampus, and thalamus (Christie et al.”

“It has been estimated that 75% of the VTA-to-ventral striatal projection is dopaminergic.(36) DAmodels of drug addiction and incentive motivation also posit influences of other chemical systems, given DA’s neuromodulatory regulation of various neuronal populations, its frequent co-release with GABA, and accordingly, t…”

“The SUM sends many fibers to widespread regions (Swanson 1982; Veazey et al. 1982), such as the cingulate cortex, the entorhinal cortex, the amygdala, the septum, the endopiriform cortex, the hypothalamic nuclei, the intralaminar thalamic nuclei and the hippocampus.”

“The AMY receives DA innervation from VTA neurons and contains moderate to high densities of D1-like and D2-like receptors (Asan, 1997; Mansour et al., 1990).”

“Swanson (1982) specifically investigated projections of the VTA and SN DA neurons by combining retrograde tract tracing with immunohistochemical detection of TH to mark DA neurons in rats.”

“However, although the frontal lobes receive strong projections from dopaminergic [dopamine (DA)] neurons in the midbrain (Swanson, 1982; Goldman-Rakic et al., 1992), and DA in the prefrontal cortex (PFC) has been associated with specific cognitive functions such as working memory and cognitive control (Miller and Cohe…”

“A general picture arises in which dopaminergic neurons are densely populated in the VTA and more so in the SNpc [11,17,18].”

“aminergic structures (90, 91) and an alternative, perhaps comple-”

“Although the anterior tip projects heavily to limbic forebrain regions, a much higher percentage of such projection neurons are dopaminergic in the rest of the VTA (Swanson, 1982).”

“The distribution of these cells is consistent with the reports of previous studies (Swanson, 1982).”

“of dopaminergic neurons have been segregated based on a variety of properties, including their projections to cortical and subcortical areas of the basal forebrain (Deutch, 1988; Fallon and Moore, 1978; Swanson, 1982).”

“Self-stimulation conditioning can also be obtained from brain areas projecting to the VTA such as the OT or the hypothalamus.(33,34) Our data reveal that the pOB, not receiving from nor sending direct synaptic contacts to the VTA, supports self-stimulation conditioning, in line with an isolated report from the early 1…”

“In septal nuclei DA ligands have been found to affect the activity of hippocampal cholinergic projections arising from the medial septal/diagonal band complex (Robinson et aI., 1979; Swanson, 1982).”

“Sawchenko PE, Swanson LW, Steinbusch HW, Verhofstad AA.”

“Nonetheless, a variety of brain and behavioral manipulations demonstrate that the nigrostriatal system displays symmetrical laterality whereas the mesolimbic system displays asymmetrical laterality which supports hemispheric specialization in rodents.”

“Along similar lines, the preferred localization of tyrosine hydroxylase-positive neurons in the medial part of the supramammillary nucleus suggests that the ventral hippocampus probably receives stronger dopaminergic inputs than the dorsal hippocampus [86], reflecting a preferred relation of the ventral hippocampus wi…”

“In the ventral tegmental area (VTA), overall 33–45% of the neurons are estimated to be non-DA neurons in rodents”

“Axons from these neurons travel via the medial forebrain bundle (MFB) into the lateral septum (Swanson, 1982; Jakab and Leranth, 1995).”

“Ventral tegmental area afferents to the prefrontal cortex maintain membrane potential ‘up’ states in pyramidal neurons via D(1) dopamine receptors.”

“In this network, DA efferents from the ventral tegmental area densely innervate cortical and forebrain structures such as the medial prefrontal cortex (mPFC), AMY and NAc (Swanson, 1982), and these structures are interconnected.”

“Importantly, VTA projections include many non-dopamine neurons (e.g. Breton et al., 2019; Swanson, 1982; Taylor et al., 2014) and these non-dopamine projections can drive aversive responses (e.g. Qi et al., 2016; Root et al., 2014), raising the possibility that dopamine functions in concert with…”

“A well-established stress-responsive role has been reported for mesocortical and mesolimbic dopaminergic pathways originating from the VTA (Homberg et al., 2002; Swanson, 1982; Thiel and Schwarting, 2001).”

“, 2003), and it has also been shown that DA neurons from the A10 region of the VTA project to hippocampus (Swanson, 1982; Gasbarri et al., 1994).”

“As it has been suggested that a relatively large proportion of the total of 18,000 DA neurons situated in the VTA bilaterally project to the NAS ( Swanson 1982 ), 500 grafted DA neurons probably represent only a small portion of the VTA DA neurons that normally bilaterally innervate the two NAS.”

“... examined the organization of the mesotelencephalic projections from the VTA and SN toward the hippocampal formation (HF) in the rat (Gasbarri et al. 1994a, b). In view of previous evidence indicating that the DA neurons of the A8 cell group contribute to the mesolimbic system projections originating from the RRF (…”