Topography and collateralization of dopaminergic projections to primary motor cortex in rats

Abstract

Dopaminergic signaling within the primary motor cortex (M1) is necessary for successful motor skill learning. Dopaminergic neurons projecting to M1 are located in the ventral tegmental area (VTA, nucleus A10) of the midbrain. It is unknown which behavioral correlates are encoded by these neurons. The objective here is to investigate whether VTA-M1 fibers are collaterals of projections to prefrontal cortex (PFC) or nucleus accumbens (NAc) or if they form a distinct pathway. In rats, multiple-site retrograde fluorescent tracers were injected into M1, PFC and the core region of the NAc and VTA sections investigated for concomitant labeling of different tracers. Dopaminergic neurons projecting to M1, PFC and NAc were found in nucleus A10 and to a lesser degree in the medial nucleus A9. Neurons show high target specificity, minimal collateral branching to other than their target area and hardly cross the midline. Whereas PFC-and NAc-projecting neurons are indistinguishably intermingled within the ventral portion of dopaminergic nuclei in middle and caudal midbrain, M1-projecting neurons are only located within the dorsal part of the rostral midbrain. Within M1, the forelimb representation receives sevenfold more dopaminergic projections than the hindlimb representation. This strong rostro-caudal gradient as well as the topographical preference to dorsal structures suggest that projections to M1 emerged late in the development of the dopaminergic systems in and form a functionally distinct system.

Large‐scale analysis reveals populational contributions of cortical spike rate and synchrony to behavioural functions

“…ventral tegmental area, VTA) and supplementary motor area (SMA) to M1 (Okano & Tanji, ; Romo & Schultz, ; Hosp et al . , ). It remains unclear how cortical neurons encode different motor initiations in rodents.…”

“…In primates, externally triggered movements are driven by signalling from the cerebellum and premotor area (PM) to M1, whereas internally triggered movements are driven by signalling from the basal ganglia (e.g. ventral tegmental area, VTA) and supplementary motor area (SMA) to M1 (Okano & Tanji, 1987;Romo & Schultz, 1992;Hosp et al 2011Hosp et al , 2015. It remains unclear how cortical neurons encode different motor initiations in rodents.…”

Multiplexed neurochemical signaling by neurons of the ventral tegmental area

“…Thus, in this review, we use the term VTA to define the midbrain A10 structure containing lateral (PBP, PN) and midline nuclei (RLi, IF, CLi). The cellular heterogeneity within the VTA subnuclei, together with findings showing that a single A10 neuron rarely innervates multiple structures (Swanson, 1982; Takada and Hattori, 1987; Lammel et al, 2008; Hosp et al 2015), suggests that the VTA utilizes highly specific projections from different sets of neurons.…”

Cortical neurons multiplex reward-related signals along with sensory and motor information

“…DA inputs to cortical areas, including primary motor (M1) and somatosensory (S1) areas, arise from the midbrain (6)(7)(8). Recent studies demonstrating the presence of a higher concentration of DA receptors in the forelimb over the hind-limb representation in rodent motor cortex (9), and impairment of motor skill acquisition resulting from blocking these DA receptors in the forelimb representation (10), point to the role of DA receptors in learning skilled forelimb movements. In agreement with this line of reasoning, animals with a rich repertoire of skilled movements, such as monkeys and humans, show a disproportionate increase in the density of DA receptors in the cortical motor areas: M1, premotor, and supplementary motor cortex (6,11,12).…”