Ventral tegmental area dopamine controls timing variability
Weber, M. A.; Sivakumar, K.; Bova, A.; Tabakovic, E.; Conlon, M.; Oya, M.; Singh, A.; Cole, R.; Espinoza, A.; Kim, Y.; Narayanan, N.
Show abstract
Precision defines successful behavior, yet the brain mechanisms promoting precision are unclear. Here, we dissect dopaminergic circuits controlling precision along a single behavioral dimension - the timing of action. We use an interval timing paradigm that requires participants to indicate their estimate of an interval of several seconds with a motor response. We find that humans with Parkinsons disease (PD) had increased timing variability that predicted PD-related cognitive deficits and executive dysfunction. Surprisingly, lesioning ventral tegmental area (VTA) dopamine neurons increased temporal variability. Further, GCaMP6s fiber photometry demonstrated that VTA dopamine neuron activity is strongly modulated at the start of temporal intervals, and that this trial start-related activity predicted temporal variability. Finally, we found that stimulation of VTA dopamine neurons improved timing by decreasing temporal variability in both intact and dopamine-depleted animals. Our data establish a model of cognitive symptoms of human PD and provide insight into the neuronal control of temporal variability, which impacts a wide range of executive functions.
Matching journals
The top 4 journals account for 50% of the predicted probability mass.
Similar papers in this journal
Similar papers in this journal
- Structural and neurophysiological alterations in Parkinson’s disease are aligned with cortical neurochemical systems 93%
- Propranolol reduces Parkinson’s tremor and inhibits tremor-related activity in the motor cortex: a placebo-controlled crossover trial 92%
- De novo missense variants in SLC32A1 cause a neurodevelopmental disorder with epilepsy due to impaired GABAergic neurotransmission 92%
Similar papers in this journal
- Neuronal titration of Snca via enhancer disruption mitigates disease onset in a Parkinson's disease mouse model 95%
- Associations between neuromelanin depletion and cortical rhythmic activity in Parkinson’s disease 93%
- Neuromelanin accumulation drives endogenous synucleinopathy in non-human primates 93%
Similar papers in this journal
- Sensory responses in dorsolateral striatum are modulated by motor activity in a dopamine-dependent manner 95%
- VTA dopamine neurons are hyperexcitable in 3xTg-AD mice due to casein kinase 2-dependent SK channel dysfunction 95%
- Synaptotagmin-1-dependent phasic axonal dopamine release is dispensable for basic motor behaviors in mice. 94%
"Similar papers" are the closest papers from that journal in the model's embedding space. They show what the match is built on, but the ranking comes mostly from a classifier over the whole training set, not from these examples alone.