Midbrain Dopamine Neurons Associated with Reward Processing Innervate the Neurogenic Subventricular Zone

Abstract

Coordinated regulation of the adult neurogenic subventricular zone (SVZ) is accomplished by a myriad of intrinsic and extrinsic factors. The neurotransmitter dopamine is one regulatory molecule implicated in SVZ function. Nigrostriatal and ventral tegmental area (VTA) midbrain dopamine neurons innervate regions adjacent to the SVZ, and dopamine synapses are found on SVZ cells. Cell division within the SVZ is decreased in humans with Parkinson’s disease and in animal models of Parkinson’s disease following exposure to toxins that selectively remove nigrostriatal neurons, suggesting that dopamine is critical for SVZ function and nigrostriatal neurons are the main suppliers of SVZ dopamine. However, when we examined the aphakia mouse, which is deficient in nigrostriatal neurons, we found no detrimental effect to SVZ proliferation or organization. Instead, dopamine innervation of the SVZ tracked to neurons at the ventrolateral boundary of the VTA. This same dopaminergic neuron population also innervated the SVZ of control mice. Characterization of these neurons revealed expression of proteins indicative of VTA neurons. Furthermore, exposure to the neurotoxin MPTP depleted neurons in the ventrolateral VTA and resulted in decreased SVZ proliferation. Together, these results reveal that dopamine signaling in the SVZ originates from a population of midbrain neurons more typically associated with motivational and reward processing.

Dopamine Receptors in Human Embryonic Stem Cell Neurodifferentiation

“…For the tissue samples, the highest TH protein levels were found in the proliferation zone of the cerebral cortex, SVZ, at GW 19 ( Fig. 2), consistent with previously published anatomical data [4,6,9]. For the D1 receptor protein, convincing bands were not seen by western blot (Fig.…”

“…For the fetal brain samples, highest TH protein levels were found in the proliferation zone of the cerebral cortex, SVZ (Fig. 2), consistent with the published anatomical data [4,9]. The next highest TH band in the fetal brain was detected in GE, consistent with the presence of DA neurons in the gangliothalamic body [49,51,55].…”

“…Tyrosine hydroxylase (TH) expression, a hallmark of dopaminergic and noradrenergic neurons, is found in the human fetal brain before all cortical layers have been formed [4][5][6], suggesting that at this early age DA is involved in proliferation, migration, and differentiation of young neurons [7][8][9]. Ambient DA was detected in follicular fluid of superovulated women [10], and human fetal brain tissue (9-10 gestational weeks [GWs]) in vitro [11].…”

Roles for Hedgehog signaling in adult organ homeostasis and repair

“…Indeed, SHH signaling has previously been demonstrated to protect dopaminergic neurons from neurotoxic effects (Dass et al, 2005;Hurtado-Lorenzo et al, 2004;Suwelack et al, 2004). As midbrain dopaminergic neurons also project to the SVZ (Lennington et al, 2011), along with other neuronal populations (Berg et al, 2013), it is possible that anterograde movement of SHH protein along axons allows the delivery of the protein to both the SVZ and striatum (Fig. 3A).…”

Dopaminergic neurons modulate GABA neuron migration in the embryonic midbrain

“…Unlike in the telencephalon, where neuronal migration has been well elucidated, in the mesencephalon this vital event has been understudied and key factors remain to be defined. Dopaminergic (DA) neurons located in the three anatomically defined areas of the ventral mesencephalon (VM) -the substantia nigra (SN), ventral tegmental area (VTA) and retrorubral field (RRF) -are involved in controlling diverse brain functions, including motor control and cognition, emotion and reward behaviors (Björklund and Dunnett, 2007;Damier et al, 1999;Ding et al, 2011;Lennington et al, 2011;Schultz, 2001;Seeman et al, 1993;Smidt and Burbach, 2007). The migration routes of DA neurons are not well understood and the related literature is contradictory (Hanaway et al, 1971;Kawano et al, 1995), while the route of GABA neurons to the VM is unknown.…”