Masse, I. | Search bioRxiv

bioRxiv2021

The calcium sensor synaptotagmin-1 is critical for phasic axonal dopamine release in the striatum and mesencephalon, but is dispensable for basic motor behaviors in mice

In Parkinsons disease (PD), motor dysfunctions only become apparent after extensive loss of DA innervation. This resilience has been hypothesized to be due to the ability of many motor behaviors to be sustained through a diffuse basal tone of DA; but experimental evidence for this is limited. Here we show that conditional deletion of the calcium sensor synaptotagmin-1 (Syt1) in DA neurons (Syt1 cKODA mice) abrogates most activity-dependent axonal DA release in the striatum and mesencephalon, leaving somatodendritic (STD) DA release intact. Strikingly, Syt1 cKODA mice showed intact performance in multiple unconditioned DA-dependent motor tasks and even in a task evaluating conditioned motivation for food. Considering that basal extracellular DA levels in the striatum were unchanged, our findings suggest that activity-dependent DA release is dispensable for such tasks and that they can be sustained by a basal tone of extracellular DA. Taken together, our findings reveal the striking resilience of DA-dependent motor functions in the context of a near-abolition of phasic DA release, shedding new light on why extensive loss of DA innervation is required to reveal motor dysfunctions in PD.

neuroscience↗

bioRxiv2019

Effects of enucleation on the direct reciprocal corticocortical connections between primary visual and somatosensory cortices of the mouse

Multisensory convergence is present in the cerebral cortex even at the initial stages of processing in the primary and low-level sensory cortices. Direct connections between primary sensory cortices are a particular feature of rodent cortical connectivity. Our previous studies have shown asymmetric projections between the primary visual and somatosensory cortices in mice. Binocular enucleation produces a relative reduction of the projections from the somatosensory cortex to the visual cortex in mice. The purpose of this study is to compare the direct reciprocal cross-modal connections between the primary visual (V1) and somatosensory (S1) cortices in intact and enucleated C57Bl/6 mice, and to determine quantitative differences in the proportion and laminar distribution of neurons and terminals in these projections. CTB labeled neurons were used to estimate the relative importance of projections between V1 and S1, and their laminar distribution used to classify them as feedback, feedforward or lateral projections. The size of axonal swellings was measured and frequency distribution determined for each cortical layer. Axon diameters were also sampled in these connections. Injections in V1 resulted in a reduced proportion of labeled cells in S1 of enucleated mice. There was a relative decrease of the projection from the somatosensory cortex to the visual cortex in enucleated mice due to a greater relative reduction of supragranular layers neurons. Enucleation otherwise had no effect on the connectivity of the somatosensory cortex with other motor and somatosensory cortices. In the projection from the visual to the somatosensory cortex in enucleated mice, the size of axonal swellings was reduced in all layers. Conversely, in the projection from the somatosensory cortex to the visual cortex, some larger swellings appeared in the supragranular layers. This shows pathway and laminar specific changes in cortical circuitry following loss of sensory afferent activity that results in changes in the relationship between visual and somatosensory cortices in the enucleated mice.

neuroscience↗