Cholinergic midbrain afferents modulate striatal circuits and shape encoding of action strategies

Nature Communications, Journal Year: 2020, Volume and Issue: 11(1)

Published: April 8, 2020

Abstract Assimilation of novel strategies into a consolidated action repertoire is crucial function for behavioral adaptation and cognitive flexibility. Acetylcholine in the striatum plays pivotal role such adaptation, its release has been causally associated with activity cholinergic interneurons. Here we show that midbrain, previously unknown source acetylcholine striatum, major contributor to transmission striatal complex. Neurons pedunculopontine laterodorsal tegmental nuclei synapse interneurons give rise excitatory responses. Furthermore, they produce uniform inhibition spiny projection neurons. Inhibition from midbrain terminals impairs association contingencies formation habits an instrumental task, mimics effects observed following These results suggest existence two hierarchically-organized modes where are modulated by neurons midbrain.

Language: Английский

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Exercise enhances motor skill learning by neurotransmitter switching in the adult midbrain

Nature Communications, Journal Year: 2020, Volume and Issue: 11(1)

Published: May 4, 2020

Abstract Physical exercise promotes motor skill learning in normal individuals and those with neurological disorders but its mechanism of action is unclear. We find that one week voluntary wheel running enhances the acquisition skills adult mice. One also induces switching from ACh to GABA expression neurons caudal pedunculopontine nucleus (cPPN). Consistent regulation skills, we show make projections substantia nigra (SN), ventral tegmental area (VTA) ventrolateral-ventromedial nuclei thalamus (VL-VM). Use viral vectors override transmitter blocks beneficial effect on learning. suggest neurotransmitter provides basis by which sustained benefits learning, presenting a target for clinical treatment movement disorders.

Language: Английский

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Anatomic resolution of neurotransmitter-specific projections to the VTA reveals diversity of GABAergic inputs

Nature Neuroscience, Journal Year: 2020, Volume and Issue: 23(8), P. 968 - 980

Published: June 15, 2020

Language: Английский

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Context-Dependent Multiplexing by Individual VTA Dopamine Neurons

Journal of Neuroscience, Journal Year: 2020, Volume and Issue: 40(39), P. 7489 - 7509

Published: Aug. 28, 2020

Dopamine (DA) neurons of the VTA track cues and rewards to generate a reward prediction error signal during Pavlovian conditioning. Here we explored how these respond self-paced, operant task in freely moving mice. The animal could trigger reward-predicting cue by remaining specific location an box for brief time before spout collection. DA were identified using DAT-Cre male mice that carried optrode with minimal impact on behavioral task. In vivo single-unit recordings revealed transient fast spiking responses correct trials, while incorrect ones activity paused, reflecting positive negative signals prediction. In parallel, majority simultaneously encoded multiple actions (e.g., movement velocity, acceleration, distance goal, licking) sustained slow firing modulation. Applying GLM, show such multiplexed encoding rewarding motor variables individual was only apparent mouse engaged Downstream targets may exploit goal-directed multiplexing adjust optimize task9s outcome. SIGNIFICANCE STATEMENT code functions, including but also motivation locomotion. about half recorded perform multiplexing: they phasic tonic modes encode, respectively, cue/reward parameters, most prominently when engages self-paced operand non-DA neurons, contrast, encode parameters regardless engagement.

Language: Английский

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A Brainstem Locomotor Circuit Drives the Activity of Speed Cells in the Medial Entorhinal Cortex

Cell Reports, Journal Year: 2020, Volume and Issue: 32(10), P. 108123 - 108123

Published: Sept. 1, 2020

Locomotion activates an array of sensory inputs that may help build the self-position map medial entorhinal cortex (MEC). In this map, speed-coding neurons are thought to dynamically update representations animal's position. A possible origin for speed signal is mesencephalic locomotor region (MLR), which critically involved in activation programs. Here, we describe, rats, a circuit connecting pedunculopontine tegmental nucleus (PPN) MLR MEC via horizontal limb diagonal band Broca (HDB). At each level pathway, locomotion linearly encoded neuronal firing rates. Optogenetic PPN cells drives and modulates activity speed-modulated HDB MEC. Our results provide evidence pathway by brainstem signals can reach cortical structures implicated navigation higher-order dynamic space.

Language: Английский

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