Direct Dopaminergic Projections from the SNc Modulate Visuomotor Transformation in the Lamprey Tectum

Abstract

Dopamine neurons in the SNc play a pivotal role in modulating motor behavior via striatum. Here, we show that the same dopamine neuron that targets striatum also sends a direct branch to the optic tectum (superior colliculus). Whenever SNc neurons are activated, both targets will therefore be affected. Visual stimuli (looming or bars) activate the dopamine neurons coding saliency and also elicit distinct motor responses mediated via tectum (eye, orienting or evasive), which are modulated by the dopamine input. Whole-cell recordings from tectal projection neurons and interneurons show that dopamine, released by SNc stimulation, increases or decreases the excitability depending on whether they express the dopamine D1 or the D2 receptor. SNc thus exerts its effects on the visuomotor system through a combined effect directly on tectum and also via striatum. This direct SNc modulation will occur regardless of striatum and represents a novel mode of motor control.

Individual Dopaminergic Neurons of Lamprey SNc/VTA Project to Both the Striatum and Optic Tectum but Restrict Co-release of Glutamate to Striatum Only

“…The lamprey homolog of the SNc/VTA, the nucleus of the posterior tuberculum, is located in the caudal diencephalon (Figure 1A) and contains dopaminergic neurons ( Figure 1B) that target striatum [13]. These striatum-projecting neurons send collaterals to brainstem motor-related centers, including the optic tectum and mesencephalic locomotor region (MLR) [1,3,14,15]. The SNc/VTA can be clearly differentiated from the cerebrospinal fluid-contacting (CSF-c) dopaminergic neurons in the mammillary area, which are significantly smaller (8.9 ± 1.2 mm, n = 240; versus 13.0 ± 2.8 mm, n = 182 in SNc/VTA; Student's t test, p < 0.01; Figure 1B), and neither project to striatum nor to tectum.…”

“…Dopaminergic neurons in the substantia nigra (SNc) innervate both striatum and the superior colliculus in mammals, as well as its homolog the optic tectum in lampreys, belonging to the oldest group of living vertebrates [1][2][3]. In the lamprey, we have previously shown that the same neuron sends axonal branches to both striatum and the optic tectum [3].…”

“…Dopaminergic neurons in the substantia nigra (SNc) innervate both striatum and the superior colliculus in mammals, as well as its homolog the optic tectum in lampreys, belonging to the oldest group of living vertebrates [1][2][3]. In the lamprey, we have previously shown that the same neuron sends axonal branches to both striatum and the optic tectum [3]. Here, we show that most neurons in the lamprey SNc and ventral tegmental area (VTA) (also referred to as the nucleus of the posterior tuberculum) express not only tyrosine hydroxylase (TH), in lamprey a marker of dopaminergic neurons [4], but also the vesicular glutamate transporter (vGluT), suggesting that glutamate is a co-transmitter.…”

“…Although glutamatergic effects may be easily detected using extracellular recordings, this is not the case for the modulatory effects elicited by dopamine. We have, however, recently shown that dopamine from the SNc/ VTA has strong modulatory effects on the excitability of tectal neurons [3]. SNc: human 0.02 0.29 0.00 5.90 [22] VTA: rat 0.40 2.50 4.00 64.00 [19] VTA: mouse 0.40 67.00 0.00 27.00 [21] VTA: human 0.11 1.70 0.50 31.50 [22] SNc/VTA: lamprey 1 2.82 15.03 83.00 96.00 this paper, Figure 1F SNc/VTA: lamprey 2 2.54 46.25 73.00 100.00 this paper, not shown…”

“…We also analyzed whether these two neurotransmitters are differentially released in different brain areas targeted by the same SNc/VTA neurons, given that release sites are segregated in micro-domains within the rodent striatum [7]. We analyzed the co-expression in neurons targeting the striatum and tectum, which both receive inputs from the same individual neurons in the SNc/VTA [3]. First, we investigated whether a glutamatergic input from the SNc/VTA to tectum and striatum is present, as suggested by the large number of dopaminergic neurons expressing vGluT.…”