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Séminaire - Juan Mena-SegoviaMidbrain circuits mediating behavioral inhibition

Abstract :

Cholinergic neurons of the midbrain, located in the pedunculopontine (PPN) and laterodorsal tegmental nuclei, are interconnected with all the basal ganglia structures, as well as with motor centers in the brainstem and medulla. Recent theories put into question whether PPN cholinergic neurons form part of a locomotor region that directly regulates the motor output, and rather suggest a modulatory role in adaptive behavior involving both motor and cognitive functions. In support of this, experimental studies in animals suggest that cholinergic neurons reinforce actions by signaling reward prediction and shape adaptations in behavior during changes in environmental contingencies.

This is further supported by clinical studies proposing that decreased cholinergic transmission originated in the PPN is associated with impaired sensorimotor integration and perseverant behavior, giving rise to some of the symptoms observed in Parkinson’s disease and progressive supranuclear palsy. Along with cholinergic neurons, GABAergic and glutamatergic neurons constitute the other two large neuronal populations of the PPN, but little is known about their contribution to basal ganglia function.

Despite the difference in connectivity and neurochemical composition of all three populations, our recent functional studies suggest that all neurons have a converging function associated with the inhibition of behavior. In my talk, I will present our recent findings based on anatomical and functional studies obtained from the dissection of these midbrain circuits and will propose a unified theory that explains their contribution to behavior. 

Selected publications

Last publications
1. Mena-Segovia J. and Bolam J.P. Rethinking the pedunculopontine nucleus: from cellular organization to function. Neuron (2017); 94: 7-18.

 2. Dautan D., Souza A.S., Huerta-Ocampo I., Valencia M., Assous M., Witten I.B., Deisseroth K., Tepper J.M., Bolam J.P., Gerdjikov T.V. and Mena-Segovia J. Segregated cholinergic transmission modulates dopamine neurons integrated in distinct functional circuits. Nature Neuroscience. (2016) 19(8): 1025-1033.

 3. Mena-Segovia J. Structural and functional considerations of the cholinergic brainstem. Journal of Neural Transmission(2016); 123(7):731-6.

 4. Dautan D., Hacioglu Bay H., Bolam J.P., Gerdjikov T. and Mena-Segovia J. Extrinsic sources of cholinergic innervation of the striatal complex: a whole-brain mapping analysis. Frontiers in Neuroanatomy (2016) 10:1. doi:10.3389/fnana.2016.00001.

 5. Petzold A., Valencia M., Pal B. and Mena-Segovia J. Decoding brain state transitions in the pedunculopontine nucleus: cooperative phasic and tonic mechanisms. Frontiers in Neural Circuits (2015) 9:68. doi: 10.3389/fncir.2015.00068.

 6. Dautan D., Huerta-Ocampo I., Witten I., Deisseroth K., Bolam J.P., Gerdjikov T. and Mena-Segovia J. A major external source of cholinergic innervation of the striatum and nucleus accumbens originates in the brainstem. Journal of Neuroscience (2014) 34: 4509-4518