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  • Lateral ventral tegmental area GABAergic and glutamatergic modulation of conditioned learning.

Lateral ventral tegmental area GABAergic and glutamatergic modulation of conditioned learning.

Cell reports (2021-03-18)
Giorgio Rizzi, Zhuoliang Li, Norbert Hogrefe, Kelly R Tan
ABSTRACT

The firing activity of dorso-medial-striatal-cholinergic interneurons (dmCINs) is a neural correlate of classical conditioning. Tonically active, they pause in response to salient stimuli, mediating acquisition of predictive cues/outcome associations. Cortical and thalamic inputs are typical of the rather limited knowledge about underlying circuitry contributing to this function. Here, we dissect the midbrain GABA and glutamate-to-dmCIN pathways and evaluate how they influence conditioned behavior. We report that midbrain neurons discriminate auditory cues and encode the association of a predictive stimulus with a footshock. Furthermore, GABA and glutamate cells form selective monosynaptic contacts onto dmCINs and di-synaptic ones via the parafascicular thalamus. Pathway-specific inhibition of each sub-circuit produces differential impairments of fear-conditioned learning. Finally, Vglut2-expressing cells discriminate between CSs although Vgat-positive neurons associate the predictive cue with the outcome. Overall, these data suggest that each component of the network carries information pertinent to sub-domains of the behavioral strategy.

MATERIALS
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Kynurenic acid, ≥98%
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4-Aminopyridine, ≥99%
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N-Butyldiethanolamine, ≥98.6%
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Triton X-100, laboratory grade
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Anti-Tyrosine Hydroxylase antibody produced in rabbit, affinity isolated antibody, buffered aqueous glycerol solution, sufficient for 10 blots
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Anti-Choline Acetyltransferase Antibody, Chemicon®, from goat