Dopaminergic axons track somatic signaling in behaving mice

Abstract

Striatal dopamine released from the axons of midbrain dopamine neurons has been linked to a wide range of functions, including movement control and reward-based learning. Recent studies have reported functional signaling differences between axons and somas of dopamine neurons, suggesting that local modulation controls dopamine release and calling into question the classical view of somatic control. However, these experiments are technically challenging, making it difficult to ensure that axonal and somatic recordings come from the same neurons, particularly given the heterogeneity of dopaminergic cell types. Here we used genetic strategies to isolate key dopaminergic neuron subtypes and monitor their axonal and somatic signaling patterns in behaving mice. Contrary to the inferences drawn from previous studies, these experiments revealed a robust correlation between somatic and axonal signaling. Thus, by exploiting a previously unknown connection between genetic and functional diversity in dopamine neurons, we establish that subtypes must be considered to understand the mechanisms of dopamine release in striatum during behavior.

Rethinking the network determinants of motor disability in Parkinson’s disease

“…In fact, transient elevation in striatal DA release at movement onset may be driven in part by ChIs and activation of presynaptic nAChRs on DA terminals ( Figure 2 ; Zhou et al, 2001 ; Ding et al, 2010 ; Threlfell et al, 2012 ; Berke, 2018 ; Kramer et al, 2022 ; Liu et al, 2022 ). Subsequent work has challenged this idea though, showing there is a correlation between striatal DA release and the spiking of cell bodies in the mesencephalon ( Azcorra et al, 2022 ).…”

Local and long-distance inputs dynamically regulate striatal acetylcholine during decision making

“…Furthermore, it is not known how much and when the potential CIN influence on DA signaling is functionally significant compared to the direct somato-dendritic modulation of DAN activity. The ability for CINs to evoke DA 3 release independently of somatic firing has been proposed as a mechanism to explain differences between DAN somatic activity and striatal DA levels 40 ; however, recent studies report robust correlation between somatic and axonal signaling 41,42 . In terms of DA-mediated inhibition of CINs, although CIN pauses can be induced by activation of D2Rs, they can also be triggered by other striatal inputs, including cortical and thalamic glutamatergic projections and long-range GABAergic VTA inputs [43][44][45] .…”